FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wang, H Madariaga, ML Wang, S Van Rooijen, N Oldenborg, PA Yang, YG AF Wang, Hui Madariaga, Maria Lucia Wang, Shumei Van Rooijen, Nico Oldenborg, Per-Arne Yang, Yong-Guang TI Lack of CD47 on nonhematopoietic cells induces split macrophage tolerance to CD47(null) cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chimera; phagocytosis; signaling regulatory protein-alpha ID INTEGRIN-ASSOCIATED PROTEIN; NATURAL-KILLER-CELLS; INTESTINAL MACROPHAGES; HEMATOPOIETIC-CELLS; MYELOID CELLS; MICE; DEPLETION; SYSTEM; PHAGOCYTOSIS; CLEARANCE AB Macrophages recognize CD47 as a marker of "self" and phagocytose CD47(null) hematopoietic cells. Using CD47 chimera models, here, we show that the phagocytic activity of macrophages against CD47null hematopoietic cells is conferred by CD47 expression on nonhematopoietic cells, and this "education" process is hematopoietic cell-independent. Macrophages in the chimeras where nonhematopoietic cells express CD47 phagocytose CD47null cells, whereas those in the chimeras lacking CD47 on nonhematopoietic cells are tolerant to CD47null cells. However, macrophages in the latter chimeras retain phagocytic activity against CD47null RBCS, demonstrating a split macrophage tolerance to CD47null hematopoietic cells. The findings highlight the potential importance of nonhematopoietic cells in the regulation of macrophage function, and suggest a previously uncharacterized mechanism of macrophage tolerance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. VUMC, VIrje Univ, Dept Mol Cell Biol, Fac Med, NL-1081 BT Amsterdam, Netherlands. Umea Univ, Sect Histrol & Cell Biol, Dept Integrat Med Biol, SE-90187 Umea, Sweden. RP Yang, YG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E Bldg 149-5102 13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P01 AI045897, R01 AI064569]; NIGMS NIH HHS [R01 GM057573, R01 GM57573] NR 34 TC 50 Z9 53 U1 1 U2 1 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 AUG 21 PY 2007 VL 104 IS 34 BP 13744 EP 13749 DI 10.1073/pnas.0702881104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 204SQ UT WOS:000249064700041 PM 17699632 ER PT J AU Kuperberg, GR AF Kuperberg, Gina R. TI Neural mechanisms of language comprehension: Challenges to syntax (vol 1146, pg 23, 2007) SO BRAIN RESEARCH LA English DT Correction C1 Tufts Univ, Dept Psychol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, Boston, MA 02115 USA. EM kuperber@nmr.mgh.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 20 PY 2007 VL 1164 BP 142 EP 142 DI 10.1016/j.brainres.2007.06.029 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 208LX UT WOS:000249321900016 ER PT J AU Ross, RW Kantoff, PW AF Ross, Robert W. Kantoff, Philip W. TI Predicting outcomes in prostate cancer: How many more nomograms do we need? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PREVENTION TRIAL; RISK; VALIDATION C1 Lank Ctr Genitourinary Oncol, Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ross, RW (reprint author), Lank Ctr Genitourinary Oncol, Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 8 TC 24 Z9 24 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 AUG 20 PY 2007 VL 25 IS 24 BP 3563 EP 3564 DI 10.1200/JCO.2007.12.2721 PG 2 WC Oncology SC Oncology GA 209VK UT WOS:000249415900001 PM 17704399 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI The Titanic and the iceberg: Prostate proton therapy and health care economics SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 3 TC 26 Z9 26 U1 1 U2 4 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 AUG 20 PY 2007 VL 25 IS 24 BP 3565 EP 3566 DI 10.1200/JCO.2007.11.9768 PG 2 WC Oncology SC Oncology GA 209VK UT WOS:000249415900002 PM 17704400 ER PT J AU Hampson, LA Joffe, S Fowler, R Verter, J Emanuel, EJ AF Hampson, Lindsay A. Joffe, Steven Fowler, Robert Verter, Joel Emanuel, Ezekiel J. TI Frequency, type, and monetary value of financial conflicts of interest in cancer clinical research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ECONOMIC-ANALYSES; INDUSTRY; TRIALS; QUALITY; DRUGS; ONCOLOGY; FACULTY AB Purpose Using data from American Society of Clinical Oncology ( ASCO) Annual Meetings, we determined the frequency, type, and monetary value of researchers' financial interests. Methods Financial disclosures for the 2004 ( 3,529 abstracts and 25,416 authors) and 2005 ( 3,556 abstracts and 26,181 authors) ASCO Annual Meetings were categorized into four groups: no author with a financial interest, research funding only, employment and leadership positions only, or at least one author with a personal financial interest. Interests were stratified by monetary value and other factors. Results In 2004 and 2005, 23% of abstracts had one or more authors with a personal financial interest. More than 75% of all personal financial interests were valued at less than $ 10,000. More than 90% of financial interests of more than $ 100,000 were employment related. Fewer than 3.5% of authors with personal financial interests had interests valued at more than $ 100,000. Overall, 6.3% ( 2004) and 2.9% ( 2005) of abstracts only had research funding, whereas 7.3% ( 2004) and 6.9% ( 2005) had only commercial employment. In 2005, 60% of plenary sessions compared with 23.1% in general poster sessions and 17.3% for publish-only abstracts reported financial ties. Personal financial interests were more common among US authors compared with non-US authors ( 9.2% v 4.2%). Conclusion About one fourth of abstracts at ASCO Annual Meetings have an author with a personal financial interest. Most personal financial interests are valued at less than $ 10,000 per year, whereas a majority valued at more than $ 100,000 are related to employees of commercial entities. C1 NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Dept Med, Boston, MA 02115 USA. RP Emanuel, EJ (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov OI Hampson, Lindsay/0000-0002-0740-7984; Joffe, Steven/0000-0002-0667-7384 FU Intramural NIH HHS NR 28 TC 16 Z9 18 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2007 VL 25 IS 24 BP 3609 EP 3614 DI 10.1200/JCO.2006.09.3633 PG 6 WC Oncology SC Oncology GA 209VK UT WOS:000249415900011 PM 17704409 ER PT J AU Schultz, KAP Ness, KK Whitton, J Recklitis, C Zebrack, B Robison, LL Zeltzer, L Mertens, AC AF Schultz, Kris Ann P. Ness, Kirsten K. Whitton, John Recklitis, Christopher Zebrack, Brad Robison, Leslie L. Zeltzer, Lonnie Mertens, Ann C. TI Behavioral and social outcomes in adolescent survivors of childhood cancer: A report from the childhood cancer survivor study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer CY JUN 09-10, 2006 CL Ontario, CANADA ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; OPSOCLONUS-MYOCLONUS-ATAXIA; QUALITY-OF-LIFE; INTRATHECAL METHOTREXATE; PSYCHOLOGICAL OUTCOMES; CRANIAL IRRADIATION; BRAIN-TUMORS; CHILDREN; NEUROBLASTOMA AB Purpose Adolescents, regardless of medical history, may face behavioral and social challenges. Cancer and related treatments represent additional challenges for teens navigating the transition from childhood to adulthood. This study was conducted to evaluate behavioral and social outcomes of adolescent childhood cancer survivors using data from the Childhood Cancer Survivor Study. Patients and Methods We evaluated 2,979 survivors and 649 siblings of cancer survivors to determine the incidence of difficulty in six behavioral and social domains ( depression/anxiety, headstrong, attention deficit, peer conflict/social withdrawal, antisocial behaviors, and social competence). Outcomes were determined by calculating parent-reported scores to questions from the behavior problem index. Results Survivors and siblings were similar in age at the time of interview ( mean: 14.8, survivors; 14.9, siblings; range, 12 to 17 years). Overall, multivariate analyses showed that survivors were 1.5 times ( 99% CI, 1.1 to 2.1) more likely than siblings to have symptoms of depression/ anxiety and 1.7 times ( 99% CI, 1.3 to 2.2) more likely to have antisocial behaviors. Scores in the depression/ anxiety, attention deficit, and antisocial domains were significantly elevated in adolescents treated for leukemia or CNS tumors when compared with siblings. In addition, survivors of neuroblastoma had difficulty in the depression/ anxiety and antisocial domains. Treatments with cranial radiation and/ or intrathecal methotrexate were specific risk factors. Conclusion Adolescent survivors of childhood cancer, especially those with a history of leukemia, CNS tumors, or neuroblastoma, may be at increased risk for adverse behavioral and social outcomes. Increased surveillance of this population, in combination with development of interventional strategies, should be a priority. C1 Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Mertens, AC (reprint author), Emory Univ, Dept Pediat, 2015 Uppergate Dr, Atlanta, GA 30322 USA. EM Ann.Mertens@choa.org FU NCI NIH HHS [U24 CA55727] NR 36 TC 134 Z9 136 U1 2 U2 19 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 AUG 20 PY 2007 VL 25 IS 24 BP 3649 EP 3656 DI 10.1200/JCO.2006.09.2486 PG 8 WC Oncology SC Oncology GA 209VK UT WOS:000249415900017 PM 17704415 ER PT J AU Muss, HB Berry, DA Cirrincione, C Budman, DR Henderson, IC Citron, ML Norton, L Winer, EP Hudis, CA AF Muss, Hyman B. Berry, Donald A. Cirrincione, Constance Budman, Daniel R. Henderson, I. Craig Citron, Marc L. Norton, Larry Winer, Eric P. Hudis, Clifford A. TI Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: The Cancer and Leukemia Group B experience 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 CONGESTIVE-HEART-FAILURE; ELDERLY-PATIENTS; TREATMENT TRIALS; RANDOMIZED-TRIAL; DOSE-DENSE; FOLLOW-UP; WOMEN; THERAPY; CYCLOPHOSPHAMIDE; SURVIVAL AB Purpose Older node-positive patients treated with newer adjuvant chemotherapy regimens have improvements in relapse-free and overall survival similar to younger patients. We compared toxicity of older and younger patients in three randomized trials of adjuvant chemotherapy. Patients and Methods Toxicity data were available for 93% of 6,642 patients enrolled. The three trials included: Cancer and Leukemia Group B ( CALGB) 8541, a comparison of cyclophosphamide, doxorubicin, and fluorouracil in three dose schedules; CALGB 9344: cyclophosphamide and doxorubicin with or without paclitaxel; and CALGB 9741: cyclophosphamide, doxorubicin, and paclitaxel every 2 versus every 3 weeks. National Cancer Institute grade 3 to 5 toxicities were compared among age groups. Results Seven percent of patients ( n = 458) were age 65 or older, 3% were 70 or older, 38% were 51 to 64, and 55% were 50 or younger. Twenty-four deaths ( 0.4%) were attributed to treatment; seven ( 1.5%) of 486 in patients 65 or older, 10 ( 0.40%) of 2,480 in patients who were 51 to 64 years, and seven ( 0.19%) of 3,676 occurred in patients younger than 50. In multivariate analysis, older patients were significantly more likely to have grade 4 hematologic toxicity, to have discontinued treatment for toxicity, or to have died of acute myeloid leukemia/myelodysplastic syndrome. There were no significant differences in grade 3 to 4 nonhematologic toxicity. Conclusion Healthy older patients who met the strict eligibility criteria for these trials had a higher rate of hematologic toxicity and treatment-related deaths than younger patients, but no increase in nonhematologic toxicity. Elderly patients treated with newer adjuvant chemotherapy regimens derive the same benefits from newer chemotherapy regimens as younger patients but should be cautioned about the increased risk of toxicity and treatment-related death. C1 Univ Vermont, Ctr Canc, Burlington, VT 05405 USA. Canc & Leukemia Grp B, Ctr Stat, Durham, NC USA. NYU, N Shore Univ Hosp, Manhasset, NY USA. Pro Hlth Care Associates, Lake Success, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Muss, HB (reprint author), Univ Vermont, Ctr Canc, 89 Beaumont Ave,Given Bldg E-214, Burlington, VT 05405 USA. EM hyman.muss@uvm.edu OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA32291, CA33601, CA35279, CA60138, CA77406, CA77651]; PHS HHS [CAII028] NR 33 TC 132 Z9 136 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 AUG 20 PY 2007 VL 25 IS 24 BP 3699 EP 3704 DI 10.1200/JCO.2007.10.9710 PG 6 WC Oncology SC Oncology GA 209VK UT WOS:000249415900024 PM 17704418 ER PT J AU Caravan, P Epstein, FH Helm, PA Zhang, ZD Das, B Shen, LH Jacques, V Dumas, S AF Caravan, Peter Epstein, Frederick H. Helm, Patrick A. Zhang, Zhaoda Das, Biplab Shen, Luhua Jacques, Vincent Dumas, Stephane TI Collagen targeted MRI contrast agent for molecular imaging of myocardial infarction SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Caravan, Peter] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Epstein, Frederick H.; Helm, Patrick A.] Univ Virginia, Dept Radiol, Charlottesville, VA 22930 USA. [Zhang, Zhaoda; Das, Biplab; Shen, Luhua; Jacques, Vincent; Dumas, Stephane] Epix Pharmaceut, Lexington, MA 02421 USA. EM pcaravan@gmail.com; fhe6b@virginia.edu; ph7t@virginia.edu; zzhang@epixpharma.com; bdas@epixpharma.com; lshen@epixpharma.com; vjacques@epixpharma.com; sdumas@epixpharma.com NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 22-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593904539 ER PT J AU Gray, N AF Gray, Nathanael TI BIOL 5-Chemical approaches toward the design of selective and nonselective protein kinase inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gray, Nathanael] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Nathanael_Gray@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 5-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900773 ER PT J AU Gupta, V Gylling, A Alonso, JL Sugimori, T Ianakiev, P Xiong, JP Arnaout, MA AF Gupta, Vineet Gylling, Annette Alonso, Jose Luis Sugimori, Takashi Ianakiev, Petre Xiong, Jiang-Ping Arnaout, M. Amin TI ORGN 721-Allosteric regulation of physiologic ligand binding to integrin CD11b/CD18 by the novel beta-tail domain SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gupta, Vineet; Gylling, Annette; Alonso, Jose Luis; Sugimori, Takashi; Ianakiev, Petre; Xiong, Jiang-Ping; Arnaout, M. Amin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Nephrol Div, Charlestown, MA 02129 USA. EM vineet_gupta@hms.harvard.edu RI Alonso, Jose Luis/G-7961-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 721-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12JA UT WOS:000207594300195 ER PT J AU Hilderbrand, SA Weissleder, R AF Hilderbrand, Scott A. Weissleder, Ralph TI pH-Sensitive cyanine dyes for optical imaging of acidic environments SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hilderbrand, Scott A.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. EM Scott_Hilderbrand@hms.harvard.edu NR 0 TC 0 Z9 0 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 101-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593906784 ER PT J AU Hong, R Cima, MJ Weissleder, R Josephson, L AF Hong, Rui Cima, Michael J. Weissleder, Ralph Josephson, Lee TI COLL 360-Magnetic resonance sensing applications of enhanced sensitivity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hong, Rui; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Cima, Michael J.] MIT, Cambridge, MA 02139 USA. EM rhong1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 360-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593902109 ER PT J AU Hong, R Cima, MJ Weissleder, R Josephson, L AF Hong, Rui Cima, Michael J. Weissleder, Ralph Josephson, Lee TI COLL 174-Magnetic field induced particle clustering and its application in viscosity measurement SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hong, Rui; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Cima, Michael J.] MIT, Cambridge, MA 02139 USA. EM rhong1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 174-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593902108 ER PT J AU Hung, DT Pierson, E Clatworthy, A Lee, J AF Hung, Deborah T. Pierson, Emily Clatworthy, Anne Lee, Jenny TI BIOL 259-Targeting virulence as a new antibiotic strategy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Broad Inst, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 259-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900753 ER PT J AU Insin, N Tracy, JB Lee, H Zimmer, JP Westervelt, RM Bawendi, MG AF Insin, Numpon Tracy, Joseph B. Lee, Hakho Zimmer, John P. Westervelt, Robert M. Bawendi, Moungi G. TI INOR 434-Incorporation of magnetic nanoparticles and quantum dots into silica microspheres SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Insin, Numpon; Zimmer, John P.; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Tracy, Joseph B.] Univ N Carolina, Kenan Labs Chem, Chapel Hill, NC 27599 USA. [Lee, Hakho] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Westervelt, Robert M.] Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. [Westervelt, Robert M.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. EM ninsin@mit.edu; jtracy@unc.edu; zimmer@mit.edu; mgb@mit.edu RI Tracy, Joseph/C-1153-2009 OI Tracy, Joseph/0000-0002-3358-3703 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 434-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593909610 ER PT J AU Kotz, KT Russom, A Irimia, D Mindrinos, M Moldawer, LL Tompkins, RG Toner, M AF Kotz, Kenneth T. Russom, Aman Irimia, Daniel Mindrinos, Michael Moldawer, Lyle L. Tompkins, Ronald G. Toner, Mehmet TI ANYL 403-Microfluidic immunoaffinity capture cassette for rapid isolation and processing of neutrophils from whole blood SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kotz, Kenneth T.; Russom, Aman; Irimia, Daniel; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA 02129 USA. [Mindrinos, Michael] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Moldawer, Lyle L.] Univ Florida, Dept Surg, Gainesville, FL 32610 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. EM kkotz@partners.org RI Russom, Aman/B-1675-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 403-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901318 ER PT J AU Macias, CE Senturk, HB Muratoglu, OK AF Macias, Celia Edith Senturk, Hatice Bodugoz Muratoglu, Orhun K. TI Dissolution of poly(vinyl alcohol) hydrogels quantified using UV-vis spectrophotometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Macias, Celia Edith; Senturk, Hatice Bodugoz; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. EM cmacias@partners.org; hsenturk@partners.org; omuratoglu@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 491-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593905685 ER PT J AU McCarthy, JR Korngold, E Jaffer, F Weissleder, R AF McCarthy, Jason R. Korngold, Ethan Jaffer, Farouc Weissleder, Ralph TI MEDI 122-Multimodal nanoagent for the diagnosis and treatment of atherosclerosis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [McCarthy, Jason R.; Korngold, Ethan; Jaffer, Farouc; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 122-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593906607 ER PT J AU Oral, E Muratoglu, OK AF Oral, Ebru Muratoglu, Orhun K. TI Effect of molecular weight and crystallization conditions on high pressure crystallized ultra-high molecular weight polyethylene SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. EM eoral@partners.org; omuratoglu@partners.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 514-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593905696 ER PT J AU Ran, CZ Pantazopoulos, P Medarova, Z Moore, A AF Ran, Chongzhao Pantazopoulos, Pamela Medarova, Zdravka Moore, Anna TI BIOL 98-Synthesis and testing of beta-cell specific Streptozotocin-derivated near infrared imaging probes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Ran, Chongzhao; Pantazopoulos, Pamela; Medarova, Zdravka; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02129 USA. EM cran@nmr.mgh.harvard.edu; PPANTAZOPOULOS@PARTNERS.ORG NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 98-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900658 ER PT J AU Riscoe, MK Kelly, JX Smilkstein, MJ Winter, RW AF Riscoe, Michael K. Kelly, Jane X. Smilkstein, Martin J. Winter, Rolf W. TI Hemozoin formation as a target for antimalarial drug design SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Riscoe, Michael K.; Kelly, Jane X.; Smilkstein, Martin J.; Winter, Rolf W.] Portland VA Med Ctr, Med Res Serv, Portland, OR 97239 USA. EM riscoem@ohsu.edu; ellyja@ohsu.edu; smilkste@ohsu.edu; winterr@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 5-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593906518 ER PT J AU Rosa, J Arnaout, MA Gupta, V AF Rosa, Jack Arnaout, M. Amin Gupta, Vineet TI MEDI 21-Novel small molecule agonists of the integrin CD11b/CD18 as in vivo chemical biology probes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rosa, Jack; Arnaout, M. Amin; Gupta, Vineet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med, Charlestown, MA 02129 USA. EM vineet_gupta@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 21-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593906606 ER PT J AU Rybak-Akimova, EV Makhlynets, O Taktak, S Flook, M Mas-Balleste, R Que, L AF Rybak-Akimova, Elena V. Makhlynets, Olga Taktak, Sonia Flook, Margaret Mas-Balleste, Ruben Que, Lawrence, Jr. TI INOR 610-Aromatic hydroxylation at a nonheme iron center SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rybak-Akimova, Elena V.; Makhlynets, Olga; Flook, Margaret] Tufts Univ, Dept Chem, Medford, MA 02155 USA. [Taktak, Sonia] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. [Taktak, Sonia] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Mas-Balleste, Ruben; Que, Lawrence, Jr.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Mas-Balleste, Ruben; Que, Lawrence, Jr.] Univ Minnesota, Ctr Met Biocatalysis, Minneapolis, MN 55455 USA. EM erybakak@tufts.edu; olga.makhlynets@tufts.edu; staktak@partners.org; que@chem.umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 610-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593908846 ER PT J AU Saffarian, S Kirchhausen, T AF Saffarian, Saveez Kirchhausen, Tomas TI PHYS 598-Live cell fluorescence visualization of clathrin coat assembly with 10nm axial resolution SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Saffarian, Saveez] Harvard Univ, Sch Med, Ctr Blood Res, CBRI, Boston, MA 02115 USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 598-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593907532 ER PT J AU Saparov, SM Pohl, P Zeidel, ML Mathai, JC AF Saparov, Sapar M. Pohl, Peter Zeidel, Mark L. Mathai, John C. TI PHYS 715-Gas permeability of lipid membranes and aquaporins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Saparov, Sapar M.] Johannes Kepler Univ Linz, Inst Biophys, A-4040 Linz, Austria. [Pohl, Peter] Univ Halle Wittenberg, Inst Med Phys & Biophys, D-06097 Halle, Germany. [Zeidel, Mark L.; Mathai, John C.] Harvard Univ, Sch Med, Dept Med, BIDMC, Boston, MA 02215 USA. [Zeidel, Mark L.; Mathai, John C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM aaa@aaa.aaa; peter.pohl@medizin.uni-halle.de; jmathai@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 715-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593907703 ER PT J AU Senturk, HB Choi, J Kung, JH Macias, CE Muratoglu, OK AF Senturk, Hatice Bodugoz Choi, Jeeyoung Kung, Jean Hsiang Macias, Celia Edith Muratoglu, Orhun K. TI Novel semicrystalline PVA hydrogel as load bearing cartilage substitute SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Senturk, Hatice Bodugoz; Choi, Jeeyoung; Kung, Jean Hsiang; Macias, Celia Edith; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. EM hsenturk@partners.org; eoral@partners.org; jchoi6@partners.org; cmacias@partners.org; omuratoglu@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 16-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593905345 ER PT J AU Seog, J Dill, JW Smith, SB Zhang, XH Cecconi, C Marqusee, S Bustamante, C Springer, TA AF Seog, Joonil Dill, Jesse W. Smith, Steven B. Zhang, Xiaohui Cecconi, Ciro Marqusee, Susan Bustamante, Carlos Springer, Timothy A. TI PHYS 665-Unfolding behavior of Rossmann fold integrin I domain measured directly using optical tweezer SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Seog, Joonil] Univ Maryland, College Pk, MD 20742 USA. [Dill, Jesse W.; Smith, Steven B.; Cecconi, Ciro] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. [Zhang, Xiaohui] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Marqusee, Susan] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Phys, Berkeley, CA 94720 USA. [Springer, Timothy A.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. EM jseog@umd.edu; xzhang@cbrinstitute.org; ciro.cecconi@gmail.com; marqusee@berkeley.edu; springer@cbrinstitute.org RI Cecconi, Ciro/K-5028-2016 OI Cecconi, Ciro/0000-0002-6101-2609 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 665-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593907539 ER PT J AU Stemp, EDA Estonactoc, A Madison, A Scala, J Ochoa, CE Schaefer, K Kurbanyan, K AF Stemp, Eric D. A. Estonactoc, Alina Madison, Amanda Scala, Julianna Ochoa, Carmen E. Schaefer, Kathryn Kurbanyan, Kristina TI Influence of guanine oxidation potential on DNA-protein crosslinking reactions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Stemp, Eric D. A.; Estonactoc, Alina; Madison, Amanda; Scala, Julianna; Ochoa, Carmen E.; Schaefer, Kathryn] Mt St Marys Coll, Dept Phys Sci & Math, Los Angeles, CA 90049 USA. [Kurbanyan, Kristina] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM amadison@msmc.la.edu; juliscal@msmc.la.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 82-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593905193 ER PT J AU Taktak, S Sosnovik, D Cima, MJ Weissleder, R Josephson, L AF Taktak, Sonia Sosnovik, David Cima, Michael J. Weissleder, Ralph Josephson, Lee TI INOR 491-NMR-based sensors using iron oxide nanoparticles SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Taktak, Sonia; Sosnovik, David; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. [Taktak, Sonia; Sosnovik, David; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Cima, Michael J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. EM staktak@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 491-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593909038 ER PT J AU Tseng, YH AF Tseng, Yu-Hua TI BIOHW 11-Role of bone morphogenetic proteins in brown adipogenesis and energy homeostasis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tseng, Yu-Hua] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 11-BIOHW PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900538 ER PT J AU Urban, JF Steenhard, NR Solano-Aguilar, GI Dawson, HD Iweala, OI Nagler, CR Noland, GS Kumar, N Anthony, RM Shea-Donohue, T Weinstock, J Gause, WC AF Urban, Joseph F., Jr. Steenhard, Nina R. Solano-Aguilar, Gloria I. Dawson, Harry D. Iweala, Onyinye I. Nagler, Cathryn R. Noland, Gregory S. Kumar, Nirbhay Anthony, Robert M. Shea-Donohue, Terez Weinstock, Joel Gause, William C. TI Infection with parasitic nematodes confounds vaccination efficacy SO VETERINARY PARASITOLOGY LA English DT Article; Proceedings Paper CT 21st International Conference of the World-Association-for-the-Advancement-of-Veterinary-Parasitology CY AUG 19-23, 2007 CL Ghent, BELGIUM SP Bayer HealthCare Anim Hlth, World Assoc Advancement Vet Parasitol, Ft Dodge Anim Hlth, Janssen Anim Hlth, Merial, Novartis Anim Hlth, Pfizer Anim Hlth DE Th2-associated immunity; immune modulating parasitic infection; cytokine gene expression; protective immunity ID ALTERNATIVELY ACTIVATED MACROPHAGES; REGULATORY T-CELLS; SCHISTOSOMA-MANSONI; IN-VIVO; RESPONSES; PROTECTION; ANTIGEN; TUBERCULOSIS; MALARIA AB T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL- 12 and IFN-gamma, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th I derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a specific example of the need for further work in this area, and for controlled field studies to assess the impact of other similar scenarios. (c) 2007 Published by Elsevier B.V. C1 USDA ARS, BHNRC, DGIL, Beltsville, MD 20705 USA. Univ Copenhagen, Danish Ctr Expt Parasitol, Dept Vet Pathobiol, DK-1870 Frederiksberg C, Denmark. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA. Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. Tufts Univ New England Med Ctr, Div Gastroenterol, Boston, MA 02111 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. RP Urban, JF (reprint author), USDA ARS, BHNRC, DGIL, Bldg 307C,Room 214 BARC E,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM joe.urban@ars.usda.gov RI Dawson, Harry/H-8242-2013; OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [AI031678, AI047089, AI049316, AI066188, R01 AI031678, R01 AI031678-06, R01 AI031678-07, R01 AI031678-08, R01 AI031678-09, R01 AI031678-10, R01 AI031678-11, R01 AI031678-12, R01 AI031678-13, R01 AI031678-14, R01 AI047089, R01 AI049316, R01 AI066188]; NIDDK NIH HHS [R01 DK058755, DK055678, DK058755, R01 DK055678, R56 DK058755] NR 28 TC 53 Z9 54 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD AUG 19 PY 2007 VL 148 IS 1 SI SI BP 14 EP 20 DI 10.1016/j.vetpar.2007.05.006 PG 7 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 196EP UT WOS:000248464800003 PM 17587500 ER PT J AU Xue, B Kim, YB Lee, A Toschi, E Bonner-Weir, S Kahn, CR Neel, BG Kahn, BB AF Xue, Bingzhong Kim, Young-Bum Lee, Anna Toschi, Elena Bonner-Weir, Susan Kahn, C. Ronald Neel, Benjamin G. Kahn, Barbara B. TI Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; OBESE SUBJECTS; LEPTIN ACTION; OB/OB MICE; MUSCLE; SENSITIVITY; ACTIVATION AB Mice heterozygous for insulin receptor (IR) and IR substrate (IRS)-1 deficiency provide a model of polygenic type 2 diabetes in which early-onset, genetically programmed insulin resistance leads to diabetes. Protein-tyrosine phosphatase 1B (PTP1B) dephosphorylates tyrosine residues in IR and possibly IRS proteins, thereby inhibiting insulin signaling. Mice lacking PTP1B are lean and have increased insulin sensitivity. To determine whether PTP1B can modify polygenic insulin resistance, we crossed PTP1B(-/-) mice with mice with a (d) under bar ouble (het) under bar erozygous deficiency of IR and IRS-1 alleles (DHet). DHet mice weighed slightly less than wild-type mice and exhibited severe insulin resistance and hyperglycemia, with similar to 35% of DHet males developing diabetes by 9-10 weeks of age. Body weight in DHet mice with PTP1B deficiency was similar to that in DHet mice. However, absence of PTP1B in DHet mice markedly improved glucose tolerance and insulin sensitivity at 10-11 weeks of age and reduced the incidence of diabetes and hyperplastic pancreatic islets at 6 months of age. Insulin-stimulated phosphorylation of IR, IRS proteins, Akt/protein kinase B, glycogen synthase kinase 3 beta, and p70(S6K) was impaired in DHet mouse muscle and liver and was differentially improved by PTP1B deficiency. In addition, increased phosphoenolpyruvate carboxykinase expression in DHet mouse liver was reversed by PTP1B deficiency. In summary, PTP1B deficiency reduces insulin resistance and hyperglycemia without altering body weight in a model of polygenic type 2 diabetes. Thus, even in the setting of high genetic risk for diabetes, reducing PTP1B is partially protective, further demonstrating its attractiveness as a target for prevention and treatment of type 2 diabetes. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, BB (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. EM bkahn@bidmc.harvard.edu FU NIDDK NIH HHS [DK66056, DK60838, DK33201, DK31036, DK57521, DK60839] NR 54 TC 32 Z9 36 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 17 PY 2007 VL 282 IS 33 BP 23829 EP 23840 DI 10.1074/jbc.M609680200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 199HK UT WOS:000248686600011 PM 17545163 ER PT J AU Saleque, S Kim, JW Rooke, HM Orkin, SH AF Saleque, Shireen Kim, Jonghwan Rooke, Heather M. Orkin, Stuart H. TI Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1 SO MOLECULAR CELL LA English DT Article ID FINGER TRANSCRIPTION FACTOR; T-CELL LYMPHOMAGENESIS; STEM-CELLS; HISTONE METHYLATION; GENE-EXPRESSION; TRANSGENIC MICE; PROTEIN GFI-1; GFI1B; REPRESSION; PROLIFERATION AB Gfi-1 and Gfi-1 bare homologous transcriptional repressors involved in diverse developmental contexts, including hernatopoiesis and oncogenesis. Transcriptional repression by Gfi proteins requires the conserved SNAG domain. To elucidate the function of Gfi proteins, we purified Gfi-1 b complexes and identified interacting proteins. Prominent among these is the corepressor CoREST, the histone demethylase LSID1, and HDACs 1 and 2. CoREST and LSD1 associate with Gfi-1/1 b via the SNAG repression domain. Gfi-1 b further recruits these cofactors to the majority of target gene promoters in vivo. Inhibition of CoREST and LSID1 perturbs differentiation of erythroid, megakaryocytic, and granulocytic cells as well as primary erythroid progenitors. LSD1 depletion derepresses Gfi targets in lineage-specific patterns, accompanied by enhanced histone 3 lysine 4 methylation at the respective promoters. Overall, we show that chromatin regulatory proteins CoREST and LSD1 mediate transcriptional repression by Gfi proteins. Lineage-restricted deployment of these cofactors; through interaction with Gfi proteins controls hematopoietic differentiation. C1 Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu NR 47 TC 168 Z9 177 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 17 PY 2007 VL 27 IS 4 BP 562 EP 572 DI 10.1016/j.molcel.2007.06.039 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 204NE UT WOS:000249050200008 PM 17707228 ER PT J AU Jallepalli, PV Pellman, D AF Jallepalli, Prasad V. Pellman, David TI Aneuploidy in the balance SO SCIENCE LA English DT Editorial Material ID SACCHAROMYCES-CEREVISIAE; CANCER-CELLS; INSTABILITY; POLYPLOIDY; EVOLUTION; DIPLOIDY; YEAST C1 Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jallepalli, PV (reprint author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, 1275 York Ave, New York, NY 10021 USA. EM jallepap@mskcc.org; david_pellman@dfci.harvard.edu FU NCI NIH HHS [CA107342, CA098537]; NIGMS NIH HHS [GM061345] NR 18 TC 6 Z9 7 U1 0 U2 2 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 AUG 17 PY 2007 VL 317 IS 5840 BP 904 EP 905 DI 10.1126/science.1146857 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200RJ UT WOS:000248780200025 PM 17702931 ER PT J AU Ji, HB Ramsey, MR Hayes, DN Fan, C McNamara, K Kozlowski, P Torrice, C Wu, MC Shimamura, T Perera, SA Liang, MC Cai, DP Naumov, GN Bao, L Contreras, CM Li, DN Chen, L Krishnamurthy, J Koivunen, J Chirieac, LR Padera, RF Bronson, RT Lindeman, NI Christiani, DC Lin, XH Shapiro, GI Janne, PA Johnson, BE Meyerson, M Kwiatkowski, DJ Castrillon, DH Bardeesy, N Sharpless, NE Wong, KK AF Ji, Hongbin Ramsey, Matthew R. Hayes, D. Neil Fan, Cheng McNamara, Kate Kozlowski, Piotr Torrice, Chad Wu, Michael C. Shimamura, Takeshi Perera, Samanthi A. Liang, Mei-Chih Cai, Dongpo Naumov, George N. Bao, Lei Contreras, Cristina M. Li, Danan Chen, Liang Krishnamurthy, Janakiraman Koivunen, Jussi Chirieac, Lucian R. Padera, Robert F. Bronson, Roderick T. Lindeman, Neal I. Christiani, David C. Lin, Xihong Shapiro, Geoffrey I. Jaenne, Pasi A. Johnson, Bruce E. Meyerson, Matthew Kwiatkowski, David J. Castrillon, Diego H. Bardeesy, Nabeel Sharpless, Norman E. Wong, Kwok-Kin TI LKB1 modulates lung cancer differentiation and metastasis SO NATURE LA English DT Article ID CONDITIONAL MOUSE MODEL; K-RAS; BREAST-CANCER; CELL; GENE; EXPRESSION; ADENOCARCINOMAS; IDENTIFICATION; TUMORIGENESIS; ACTIVATION AB Germline mutation in serine/ threonine kinase 11 ( STK11, also called LKB1) results in Peutz - Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers(1). Although uncommon in most sporadic cancers(2), inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines(3-5). Here we used a somatically activatable mutant Kras- driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/ Arf ( also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1- deficient tumours demonstrated shorter latency, an expanded histological spectrum ( adeno-, squamous and large- cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/ Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ludwig Ctr Dana Farber, Harvard Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Translat Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM nelbardeesy@partners.org; nes@med.unc.edu; kwong1@partners.org RI Meyerson, Matthew/E-7123-2012; OI Ramsey, Matthew/0000-0003-2402-8502; Hayes, D. Neil/0000-0001-6203-7771; Wu, Michael C./0000-0002-3357-6570; wong, kwok kin/0000-0001-6323-235X NR 36 TC 451 Z9 482 U1 7 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 16 PY 2007 VL 448 IS 7155 BP 807 EP U7 DI 10.1038/nature06030 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200HJ UT WOS:000248754200040 PM 17676035 ER PT J AU Seelig, B Szostak, JW AF Seelig, Burckhard Szostak, Jack W. TI Selection and evolution of enzymes from a partially randomized non-catalytic scaffold SO NATURE LA English DT Article ID MESSENGER-RNA DISPLAY; IN-VITRO SELECTION; DIRECTED EVOLUTION; INDUSTRIAL BIOCATALYSIS; COMPUTATIONAL DESIGN; ACTIVE-SITE; SEQUENCES; PROTEINS; PEPTIDES; IDENTIFICATION AB Enzymes are exceptional catalysts that facilitate a wide variety of reactions under mild conditions, achieving high rate-enhancements with excellent chemo-, regio- and stereoselectivities. There is considerable interest in developing new enzymes for the synthesis of chemicals and pharmaceuticals(1-3) and as tools for molecular biology. Methods have been developed for modifying and improving existing enzymes through screening, selection and directed evolution(4,5). However, the design and evolution of truly novel enzymes has relied on extensive knowledge of the mechanism of the reaction(6-10). Here we show that genuinely new enzymatic activities can be created de novo without the need for prior mechanistic information by selection from a naive protein library of very high diversity, with product formation as the sole selection criterion. We used messenger RNA display, in which proteins are covalently linked to their encoding mRNA(11), to select for functional proteins from an in vitro translated protein library of > 10(12) independent sequences without the constraints imposed by any in vivo step. This technique has been used to evolve new peptides and proteins that can bind a specific ligand(12-18), from both random- sequence libraries(12,14-16) and libraries based on a known protein fold(17,18). We now describe the isolation of novel RNA ligases from a library that is based on a zinc finger scaffold(18,19), followed by in vitro directed evolution to further optimize these enzymes. The resulting ligases exhibit multiple turnover with rate enhancements of more than two- million- fold. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Simches Res Ctr 7215, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, CCIB, Simches Res Ctr 7215, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Simches Res Ctr 7215, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu RI Seelig, Burckhard/D-1042-2013 OI Seelig, Burckhard/0000-0001-8598-0586 FU Howard Hughes Medical Institute NR 37 TC 116 Z9 120 U1 2 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 16 PY 2007 VL 448 IS 7155 BP 828 EP U13 DI 10.1038/nature06032 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200HJ UT WOS:000248754200045 PM 17700701 ER PT J AU Murali, MR Mackool, BT Muse, VV Zembowicz, A Ferry, JA Mitsuma, SF Zembowicz, A Robinson, DR Axelrod, L AF Murali, Mandakolathur R. Mackool, Bonnie T. Muse, Victorine V. Zembowicz, Artur Ferry, Judith A. Mitsuma, Sheila F. Zembowicz, Artur Robinson, Dwight R. Axelrod, Lloyd TI A 60-year-old man with fever, odynophagia, weight loss, and rash - Systemic lupus erythematosus with cutaneous involvement, lupus nephritis, lupus lymphadenitis, and pulmonary vasculitis. Atherosclerotic coronary artery disease with acute myocardial infarction. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICOPATHOLOGICAL ANALYSIS; INFECTION; LYMPHADENOPATHY; MANIFESTATIONS; FINGERPRINT; COMPLEMENT; DEFICIENCY; DEPOSITS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, 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 Dermatol, 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 Murali, MR (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 27 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 16 PY 2007 VL 357 IS 7 BP 692 EP 701 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 200EF UT WOS:000248746000011 PM 17699820 ER PT J AU Leung, JV Mann, S Leung, FV AF Leung, J. W. Mann, S. Leung, F. Vv. TI Options for screening colonoscopy without sedation: a pilot study in United States veterans SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PATIENT-CONTROLLED SEDATION; RANDOMIZED CONTROLLED-TRIAL; ROUTINE AB Background The direct and indirect costs of sedation limit access to screening colonoscopy amongst United States veterans. Aim To determine if offering the option of sedation on-demand reduces the need for sedation. Design A retrospective review of prospectively collected performance improvement data in an open access screening colonoscopy programme. Setting Performance improvement programme to minimize the burden of sedation at a single VA Medical Center. Subjects 44 consecutive veterans who accepted the option of sedation on-demand. They could choose to have premedications before the start of colonoscopy, or to begin colonoscopy without premedications and receive the medications upon their request during the examination. Method Two experienced endoscopists assisted by experienced nurse assistants performed all of the examinations. Insertion of the colonoscope was aided by infusion of warm water through the colonoscope without air insufflation. Medications were administered at the veterans' request. Results Offering the option of sedation on-demand to 44 consecutive veterans permitted 52% (N= 23) of the veterans to complete screening colonoscopy without any sedation. Conclusions This novel approach of sedation on-demand and water infusion for screening colonoscopy deserves to be further evaluated in a randomized-controlled study amongst patients undergoing colorectal cancer screening. C1 Vet Affairs N Calif Hlth Care Syst, Gastroenterol Sect, Sacramento VA Med Ctr, Mather, CA 95655 USA. Univ Calif Davis, Med Ctr, Div Gastroenterol & Hepatol, Davis, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol Med & Res Serv, Los Angeles, CA USA. RP Leung, JV (reprint author), Vet Affairs N Calif Hlth Care Syst, Gastroenterol Sect, Sacramento VA Med Ctr, Hosp Way, Mather, CA 95655 USA. EM jwleung@ucdavis.edu NR 21 TC 50 Z9 50 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD AUG 15 PY 2007 VL 26 IS 4 BP 627 EP 631 DI 10.1111/j.1365-2036.2007.03404.x PG 5 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 202FK UT WOS:000248887200011 PM 17661766 ER PT J AU Grant, RW AF Grant, Richard W. TI Invited commentary: Untangling the web of diabetes causality in African Americans SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE African Americans; diabetes mellitus; genetics; housing; prediabetic state; questionnaires; residence characteristics ID CARDIOVASCULAR-DISEASE; ETHNIC-DIFFERENCES; WHITE ADULTS; DISPARITIES; MORTALITY; HEALTH; RISK; CARE; RACE; COMPLICATIONS AB Diabetes is more prevalent and its consequences more severe in African Americans than in Whites. Efforts to understand and eliminate the root causes of disparities in the prediabetic state offer the potential to reduce the tremendous "downstream" costs of diabetes for patients and society. The accompanying study by Schootman et al. (Am J Epidemiol 2007; 166:379-387) presents provocative new data on the apparently significant role of an individual's own housing condition in the odds of subsequent diabetes development. Despite methodological limitations in measurement and adjustment for confounding, this paper offers new insights into potential mediators of diabetes development. Efforts to effectively address the problem of disparities in the prediabetic state will require greater interdisciplinary collaboration between unfamiliar disciplines and wider implementation of the randomized clinical trial design. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50-9 Staniford St, Boston, MA 02114 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452] NR 21 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2007 VL 166 IS 4 BP 388 EP 390 DI 10.1093/aje/kwm187 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 197XX UT WOS:000248591700003 PM 17625221 ER PT J AU Pober, BR Morris, CA AF Pober, Barbara R. Morris, Colleen A. TI Diagnosis and management of medical problems in adults with Williams-Beuren syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE Williams syndrome; medical management in adults with mental retardation ID SUPRAVALVULAR AORTIC-STENOSIS; AUTOSOMAL-DOMINANT INHERITANCE; ELFIN FACE SYNDROME; SUDDEN-DEATH; VOIDING DYSFUNCTION; NATURAL-HISTORY; PREVALENCE; CHILDREN; ABNORMALITIES; MORPHOLOGY AB Williams-Beuren syndrome (WBS) is a multi-system disorder that requires ongoing management by a primary care physician familiar with the natural history and common medical problems associated with the condition. Some abnormalities are unique to WBS, such as the elastin arteriopathy that often manifests as supravalvar aortic stenosis and hypertension. Still other features, such as diverticulosis, are seen in the general population but tend to present earlier in WBS. Life long monitoring of the cardiovascular and endocrine systems is essential to the clinical management of individuals with Williams-Beuren syndrome. Constipation should be aggressively managed, and symptoms of abdominal pain should prompt an evaluation for diverticulosis/diverticulitis. While the mean IQ of WBS is in the mild mental retardation range, difficulties with attention and anxiety are more likely to negatively impact independent functioning in the adult with WBS. There is no evidence for decline in cognitive ability over time, but adaptive functioning may be improved with treatment of anxiety by both behavior and medical modalities. (c) 2007 Wiley-Liss, Inc. C1 Univ Nevada, Sch Med, Dept Pediat Genet, Div Genet, Las Vegas, NV 89102 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. MassGen Hosp Children, Dept Pediat, Boston, MA USA. RP Morris, CA (reprint author), Univ Nevada, Sch Med, Dept Pediat Genet, Div Genet, 2040 W Charleston Blvd,Suite 401, Las Vegas, NV 89102 USA. EM cam@unr.edu FU NINDS NIH HHS [NS35102] NR 79 TC 35 Z9 35 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD AUG 15 PY 2007 VL 145C IS 3 BP 280 EP 290 DI 10.1002/ajmg.c.30139 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 203UL UT WOS:000248999400009 PM 17639596 ER PT J AU Cooper, GS Treadwell, EL Clair, EW Gilkeson, GS Dooley, MA AF Cooper, Glinda S. Treadwell, Edward L. Clair, E. William St. Gilkeson, Gary S. Dooley, Mary Anne TI Sociodemographic associations with early disease damage in patients with systemic lupus erythematosus SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE ethnicity; income; age; lupus ID 3 ETHNIC-GROUPS; COLLABORATING CLINICS/AMERICAN-COLLEGE; SOCIOECONOMIC-STATUS; RISK-FACTORS; INDEX; MORTALITY; RACE; PREDICTOR; SURVIVAL AB Objective. To examine the extent of organ damage among recently diagnosed patients with systemic lupus erythematosus (SLE), and to assess the association between sociodemographic variables and total damage and organ-specific damage scores. Methods. We evaluated damage in 132 patients with SLE (70 African Americans and 62 whites), 2-6 years (median 4 years) after diagnosis, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The associations between demographic characteristics and total damage and organ-specific damage measures were evaluated using logistic regression, adjusting for age, income, and ethnicity. Results. A total of 61% of patients scored >= 1 point on the damage index. Damage was most prevalent in the musculoskeletal (28%), skin (20%), neuropsychiatric (16%), and renal (12%) subscales. African American ethnicity and lower household income were independently associated with total damage scores (score >= 2: adjusted odds ratio [95% confidence interval] 6.0 [2.3-16.2] in African Americans and 2.7 [1.1-6.7] in patients with an annual household income <=$30,000). The odds of having skin damage, alopecia, or diabetes were at least 5 times higher in African Americans compared with whites, but ethnicity was not associated with renal damage (adjusted odds ratio 1.6, 95% confidence interval 0.40-6.1). Conclusion. Considerable damage is seen in SLE patients early in the disease course, and the pattern varies between ethnic groups. This analysis also highlights the importance of sociodemographic characteristics (particularly income) in predicting damage. C1 US EPA, NCEA, Washington, DC 20460 USA. E Carolina Univ, Sch Med, Greenville, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Med Univ S Carolina, Charleston, SC USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. Univ N Carolina, Chapel Hill, NC USA. RP Cooper, GS (reprint author), US EPA, NCEA, 8601-D,1200 Penn Ave NW, Washington, DC 20460 USA. EM cooper.glindal@epa.gov FU Intramural NIH HHS; NIEHS NIH HHS [N01-ES-85433, Z01-ES-49023] NR 18 TC 38 Z9 40 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD AUG 15 PY 2007 VL 57 IS 6 BP 993 EP 999 DI 10.1002/art.22894 PG 7 WC Rheumatology SC Rheumatology GA 199OT UT WOS:000248705800015 PM 17665464 ER PT J AU Yu, HY Jansen, R Stolovitzky, G Gerstein, M AF Yu, Haiyuan Jansen, Ronald Stolovitzky, Gustavo Gerstein, Mark TI Total ancestry measure: quantifying the similarity in tree-like classification, with genomic applications SO BIOINFORMATICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ANNOTATION TRANSFER; EXPRESSION DATA; WHOLE GENOMES; GENE ONTOLOGY; PROTEINS; PREDICTION; NETWORKS; PATHWAYS; INSIGHTS AB Motivation: Many classifications of protein function such as Gene Ontology (GO) are organized in directed acyclic graph (DAG) structures. In these classifications, the proteins are terminal leaf nodes; the categories 'above' them are functional annotations at various levels of specialization and the computation of a numerical measure of relatedness between two arbitrary proteins is an important proteomics problem. Moreover, analogous problems are important in other contexts in large-scale information organization e. g. the Wikipedia online encyclopedia and the Yahoo and DMOZ web page classification schemes. Results: Here we develop a simple probabilistic approach for computing this relatedness quantity, which we call the total ancestry method. Our measure is based on counting the number of leaf nodes that share exactly the same set of 'higher up' category nodes in comparison to the total number of classified pairs (i. e. the chance for the same total ancestry). We show such a measure is associated with a power-law distribution, allowing for the quick assessment of the statistical significance of shared functional annotations. We formally compare it with other quantitative functional similarity measures (such as, shortest path within a DAG, lowest common ancestor shared and Azuaje's information-theoretic similarity) and provide concrete metrics to assess differences. Finally, we provide a practical implementation for our total ancestry measure for GO and the MIPS functional catalog and give two applications of it in specific functional genomics contexts. Availability: The implementations and results are available through our supplementary website at: http://gersteinlab.org/proj/funcsim Contact: mark. gerstein@yale.edu Supplementary information: Supplementary data are available at Bioinformatics online. C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. Harvard Univ, Dept Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. IBM Computat Biol Ctr, TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA. RP Gerstein, M (reprint author), Yale Univ, Dept Mol Biophys & Biochem, 266 Whitney Ave,PO Box 208114, New Haven, CT 06520 USA. EM mark.gerstein@yale.edu FU NHGRI NIH HHS [P50 HG02357-01] NR 32 TC 35 Z9 36 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 15 PY 2007 VL 23 IS 16 BP 2163 EP 2173 DI 10.1093/bioinformatics/btm291 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 215OG UT WOS:000249818300017 PM 17540677 ER PT J AU Bartzokis, G AF Bartzokis, George TI Acetylcholinesterase inhibitors may improve myelin integrity SO BIOLOGICAL PSYCHIATRY LA English DT Review DE AAMI; acetylcholinesterase; ADHD; Alzheimer; cholinergic; cognition; MCI; oligodendrocyte; schizophrenia; white matter ID MILD COGNITIVE IMPAIRMENT; CHOLINE-ACETYLTRANSFERASE ACTIVITY; MATTER STRUCTURAL INTEGRITY; EARLY ALZHEIMERS-DISEASE; WHITE-MATTER; HUMAN BRAIN; NICOTINIC RECEPTORS; PARKINSONS-DISEASE; CEREBRAL-CORTEX; HIPPOCAMPAL-FORMATION AB Recent clinical trials have revealed that cholinergic treatments are efficacious in a wide spectrum of neuropsychiatric disorders that span the entire human lifespan and include disorders without cholinergic deficits. Furthermore, some clinical and epidemiological data suggest that cholinergic treatments have disease modifying/preventive effects. It is proposed that these observations can be usefully understood in a myelin-centered model of the human brain. The model proposes that the human brain's extensive myelination is the central evolutionary change that defines our uniqueness as a species and our unique vulnerability to highly prevalent neuropsychiatric disorders. Within the framework of this model the clinical, biochemical, and epidemiologic data can be reinterpreted to suggest that nonsynaptic effects of cholinergic treatments on the process of myelination and myelin repair contributes to their mechanism of action and especially to their disease modifying/preventive effects. The ability to test the model in human populations with safe and noninvasive imaging technologies makes it possible to undertake novel clinical trial efforts directed at primary prevention of some of the most prevalent and devastating of human disorders. C1 Univ Calif Los Angeles, Rush Alzheimers Dis Ctr, Div Brain Mapping,Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Rush Alzheimers Dis Ctr, Div Brain Mapping,Dept Neurol, Lab Neuroimaging, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG16570, R01 AG027342]; NIMH NIH HHS [MH0266029] NR 124 TC 21 Z9 21 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 2007 VL 62 IS 4 BP 294 EP 301 DI 10.1016/j.biopsych.2006.08.020 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 198WL UT WOS:000248658100003 PM 17070782 ER PT J AU Tefferi, A Thiele, J Orazi, A Kvasnicka, HM Barbui, T Hanson, CA Barosi, G Verstovsek, S Birgegard, G Mesa, R Reilly, JT Gisslinger, H Vannucchi, AM Cervantes, F Finazzi, G Hoffman, R Gilliland, DG Bloomfield, CD Vardiman, JW AF Tefferi, Ayalew Thiele, Juergen Orazi, Attilio Kvasnicka, Hans Michael Barbui, Tiziano Hanson, Curtis A. Barosi, Giovanni Verstovsek, Srdan Birgegard, Gunnar Mesa, Ruben Reilly, John T. Gisslinger, Heinz Vannucchi, Alessandro M. Cervantes, Francisco Finazzi, Guido Hoffman, Ronald Gilliland, D. Gary Bloomfield, Clara D. Vardiman, James W. TI Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelotibrosis: recommendations from an ad hoc international expert panel SO BLOOD LA English DT Article ID JAK2 V617F MUTATION; CHRONIC MYELOPROLIFERATIVE DISORDERS; TYROSINE KINASE MUTATION; BONE-MARROW BIOPSIES; CHRONIC IDIOPATHIC MYELOFIBROSIS; RINGED SIDEROBLASTS; MARKED THROMBOCYTOSIS; MYELOID METAPLASIA; REFRACTORY-ANEMIA; CYTOGENETIC FINDINGS AB The Janus kinase 2 mutation, JAK2617V> F, is myelold neoplasm-specific; its presence excludes secondary polycythemia, thrombocytosis, or bone marrow fibrosis from other causes. Furthermore, JAK2617V>F or a JAK2 exon 12 mutation is present in virtually all patients with polycythemia vera (PV), whereas JAK2617V>F also occurs in approximately half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Therefore, JAK2 mutation screening holds the promise of a decisive diagnostic test in PV while being complementary to histology for the diagnosis of ET and PMF; the combination of molecular testing and histologic review should also facilitate diagnosis of ET associated with borderline thrombocytosis. Accordingly, revision of the current World Health Organization (WHO) diagnostic criteria for PV, ET, and PMF is warranted; JAK2 mutation analysis should be listed as a major criterion for PV diagnosis, and the platelet count threshold for ET diagnosis can be lowered from 600 to 450 x 10(9)/L. The current document was prepared by an international expert panel of pathologists and clinical investigators in myeloproliferative disorders; it was subsequently presented to members of the Clinical Advisory Committee for the revision of the WHO Classification of Myeloid Neoplasms, who endorsed the document and recommended its adoption by the WHO. C1 Mayo Clin, Rochester, MN 55905 USA. Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. Indiana Univ, Sch Med, Indianapolis, IN USA. Osped Riuniti Bergamo, I-24100 Bergamo, Italy. Policlin San Matteo, Ist Ricovero & Cura Carattere Sci, I-27100 Pavia, Italy. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Uppsala Hosp, Uppsala, Sweden. Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England. Med Univ Vienna, Vienna, Austria. Univ Florence, Florence, Italy. Univ Barcelona, Inst Invest Biomed August Pi Sunyer, Barcelona, Spain. Univ Illinois, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Tefferi, A (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu RI kvasnicka, hans michael/H-7606-2012; Kvasnicka, Hans Michael/E-7993-2011 OI Kvasnicka, Hans Michael/0000-0002-3081-1395 NR 50 TC 516 Z9 557 U1 4 U2 19 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 AUG 15 PY 2007 VL 110 IS 4 BP 1092 EP 1097 DI 10.1182/blood-2007-04-083501 PG 6 WC Hematology SC Hematology GA 198VJ UT WOS:000248655300009 PM 17488875 ER PT J AU Nachman, JB Heerema, NA Sather, H Camitta, B Forestier, E Harrison, CJ Dastugue, N Schrappe, M Pui, CH Basso, G Silverman, LB Janka-Schaub, GE AF Nachman, James B. Heerema, Nyla A. Sather, Harland Camitta, Bruce Forestier, Erik Harrison, Christine J. Dastugue, Nicole Schrappe, Martin Pui, Ching-Hon Basso, Giuseppe Silverman, Lewis B. Janka-Schaub, Gritta E. TI Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia SO BLOOD LA English DT Article ID POOR-PROGNOSIS; CHROMOSOMES AB One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploldly (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% 4.4% and 49.80/6 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P=.01; 8-year estimate, 52.2% vs 30.1 9/6) and OS (P =.017; 691% vs 37.50/6). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted worse EFS but similar OS. Doubling of the hypodiplold clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33 39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy. C1 Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. Ohio State Univ, British Columbia Childrens Hosp, Columbus, OH 43210 USA. Operat Ctr, Childrens Oncol Grp, Arcadia, CA USA. Med Coll Wisconsin, Childrens Hosp Wisconsin, Midwest Childrens Canc Ctr, Dept Pediat, Milwaukee, WI 53226 USA. Umea Univ, Dept Clin Sci & Paediat, Umea, Sweden. Univ Southampton, Canc Sci Div, Leukaemia Res Cytogenet Grp, Southampton, Hants, England. Hop Purpan, Hematol Lab, Toulouse, France. Univ Hosp Schwanenweg, Dept Pediat, Kiel, Germany. Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Memphis, TN USA. Univ Padua, Dept Pediat, Padua, Italy. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA. Univ Hamburg, Childrens Univ Hosp, Dept Pediat Hematol & Oncol, Hamburg, Germany. RP Nachman, JB (reprint author), Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. EM jnachman@peds.bsd.uchicago.edu RI Schrappe, Martin/A-8109-2010; OI BASSO, GIUSEPPE/0000-0002-2634-9302 FU NCI NIH HHS [P01 CA68484, P30 CA021765, U10 CA 98543, U10 CA098543, CA21765, P01 CA068484] NR 10 TC 110 Z9 115 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 AUG 15 PY 2007 VL 110 IS 4 BP 1112 EP 1115 DI 10.1182/blood-2006-07-038299 PG 4 WC Hematology SC Hematology GA 198VJ UT WOS:000248655300012 PM 17473063 ER PT J AU Bilimoria, KY Bentrem, DJ Ko, CY Ritchey, J Stewart, AK Winchester, DP Talamonti, MS AF Bilimoria, Karl Y. Bentrem, David J. Ko, Clifford Y. Ritchey, Jamie Stewart, Andrew K. Winchester, David P. Talamonti, Mark S. TI Validation of the 6th Edition AJCC Pancreatic Cancer Staging System - Report from the National Cancer Database SO CANCER LA English DT Article DE pancreatic neoplasm; staging; surgery; survival; National Cancer Data Base AB BACKGROUND. with the development of stage-specific treatments for pancreatic cancer, controversies exist concerning optimal clinical and pathologic staging. The most recent edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 6(th) Edition included some notable modifications. In anticipation of the 7(th) edition's publication, the authors evaluated the predictive ability of the current pancreatic adenocarcinoma staging system. METHODS. By using the National Cancer Data Base (1992-1998), 121,713 patients were identified with pancreatic adenocarcinoma. All patients were restaged by AJCC 6(th) edition guidelines. Stage-specific overall survival was estimated by using the Kaplan-Meier method and compared with log-rank tests. Concordance indices were calculated to evaluate the discriminatory power of the staging system. Cox modeling was used to determine the relative impact of T, N, and M classification on survival. RESULTS. For all patients, there was 5-year survival discrimination by stage (P <.0001). For patients who underwent pancreatectomy, stage predicted 5-year survival: stage IA, 31.4%; IB, 27.2%; IIA, 15.7%; IIB, 7.7%; III, 6.8%; IV, 2.8% (P <.0001). The concordance index for the staging system was 0.631 for all patients, 0.613 for those who underwent pancreatectomy, and 0.596 for patients who did not undergo resection. In patients who under-went pancreatectomy, tumor size, nodal status, and distant metastases were independent predictors of survival (P <.0001). CONCLUSIONS. This is the first large-scale validation of the pancreatic cancer staging system. AJCC 6(th) edition staging guidelines are accurate with respect to survival. Further investigation is needed to integrate new molecular and biochemical markers into the staging scheme. C1 Northwestern Univ, Dept Surg, Div Surg Oncol, Chicago, IL 60611 USA. Natl Canc Data Base, Amer Coll Surg, Canc Program, Chicago, IL USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Talamonti, MS (reprint author), Northwestern Univ, Dept Surg, Div Surg Oncol, Galter 10-105,675 N St Clair St, Chicago, IL 60611 USA. EM mtalamonti@nmff.org NR 10 TC 182 Z9 190 U1 2 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2007 VL 110 IS 4 BP 738 EP 744 DI 10.1002/cncr.22852 PG 7 WC Oncology SC Oncology GA 197WH UT WOS:000248586700005 PM 17580363 ER PT J AU Dreicer, R Li, SL Manola, J Haas, NB Roth, BJ Wilding, G AF Dreicer, Robert Li, Shuli Manola, Judith Haas, Naomi B. Roth, Bruce J. Wilding, George TI Phase 2 trial of epothilone B analog BMS-247550 (ixabepilone) in advanced carcinoma of the Urothelium (E3800) - A trial of the Eastern Cooperative Oncology Group SO CANCER LA English DT Article DE ixabepilone; phase 2 trial; urothelial carcinoma ID TRANSITIONAL-CELL CARCINOMA; BLADDER-CANCER; II TRIAL; PACLITAXEL; CHEMOTHERAPY; CISPLATIN; IFOSFAMIDE; DOCETAXEL; METHOTREXATE; MULTICENTER AB BACKGROUND. Paclitaxel and docetaxel are active agents in advanced urothelial cancer. BMS-247550 (ixabepilone) has activity in preclinical models in paclitaxel resistant models. A phase 2 trial of this epothilone was performed to determine the activity and toxicity of this agent in a multi-institutional setting in patients previously treated with I prior chemotherapy regimen. METHODS. Forty-five patients with advanced urothelial carcinoma were treated with BMS-247550 40 mg/m(2) over 3 hours intravenously on Day 1 of a 21-day cycle and continued therapy until progression or unacceptable toxicity. RESULTS. Five patients obtained an objective partial response (PR) among the 42 eligible patients for an overall response rate of 11.9% (90% confidence interval [5.3%, 26.5%]). Median overall survival of the group was 8 months. Toxicity was moderate with granulocytopenia, fatigue, and sensory neuropathy being the most common side effects noted. CONCLUSIONS. BMS-247550 (ixabepilone) has very modest activity as a second-line therapy for advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and sensory neuropathy was common. C1 Cleveland Clin, Dept Solid Tumor Oncol, Cleveland, OH 44195 USA. Cleveland Clin, Urol Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Dept Biostat Sci & Computat Biol, Boston, MA USA. Fox Chase Canc Ctr, Philadelphia, PA USA. Vanderbilt Ingram, Nashville, TN USA. Univ Wisconsin, Clin Canc Ctr, Madison, WI USA. RP Dreicer, R (reprint author), Cleveland Clin, Dept Solid Tumor Oncol, 9500 Euclid Ave R35, Cleveland, OH 44195 USA. EM dreicer@ccf.org FU NCI NIH HHS [CA21115, CA49957, CA21076, CA66636, CA27525, CA23318] NR 23 TC 58 Z9 58 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2007 VL 110 IS 4 BP 759 EP 763 DI 10.1002/cncr.22839 PG 5 WC Oncology SC Oncology GA 197WH UT WOS:000248586700008 PM 17594721 ER PT J AU Landis, MW Brown, NE Baker, GL Shifrin, A Das, M Geng, Y Sicinski, P Hinds, PW AF Landis, Mark W. Brown, Nelson E. Baker, Gregory L. Shifrin, Anna Das, Manjusri Geng, Yan Sicinski, Piotr Hinds, Philip W. TI The LxCxE pRb interaction domain of cyclin D1 is dispensable for murine development SO CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; SQUAMOUS-CELL CARCINOMA; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE; REPRESS TRANSCRIPTION; GROWTH ARREST; GENE-PRODUCT; E1A PROTEINS; AMPLIFICATION; P27(KIP1) AB Cyclin D1 is a multifunctional, tumor-associated protein that interacts with pRb via a conserved LxCxE motif, activates a kinase partner, directs the phosphorylation of pRb, activates cyclin E-cyclin-dependent kinase 2 (cdk2) by titrating Cip/Kip cdk inhibitors, and modulates the activity of a variety of transcription factors. It is thought that some of the proproliferative function of cyclin D1 is exerted by LxCxE-dependent binding to the pRb pocket domain, which might interfere with the ability of pRb to repress transcription by recruiting cellular chromatin remodeling proteins to E2F-dependent promoters. To test the importance of the LxCxE domain in vivo, we have generated a "knock-in" mouse by replacing the wild-type cyclin D1 gene with a mutant allele precisely lacking the nucleotides encoding the LxCxE domain. Analysis of this mouse has shown that the LxCxE protein is biochemically similar to wild-type cyclin D1 in all tested respects. Moreover, we were unable to detect abnormalities in growth, retinal development, mammary gland development, or tumorigenesis, all of which are affected by deleting cyclin D1. Although we cannot exclude the presence of subtle defects, these results suggest that the LxCxE domain of cyclin D1 is not necessary for function despite the absolute conservation of this motif in the D-type cyclins from plants and vertebrates. C1 Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Hinds, PW (reprint author), Tufts Univ New England Med Ctr, Mol Oncol Res Inst, 750 Washington St 5609, Boston, MA 02111 USA. EM phinds@tufts-nemc.org FU NCI NIH HHS [CA096527, CA083688] NR 49 TC 5 Z9 5 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 AUG 15 PY 2007 VL 67 IS 16 BP 7613 EP 7620 DI 10.1158/0008-5472.CAN-07-1207 PG 8 WC Oncology SC Oncology GA 200XJ UT WOS:000248795800010 PM 17699765 ER PT J AU Wolpin, BM Michaud, DS Giovannucci, EL Schernhammer, ES Stampfer, MJ Manson, JE Cochrane, BB Rohan, TE Ma, J Pollak, MN Fuchs, CS AF Wolpin, Brian M. Michaud, Dominique S. Giovannucci, Edward L. Schernhammer, Eva S. Stampfer, Meir J. Manson, JoAnn E. Cochrane, Barbara B. Rohan, Thomas E. Ma, Jing Pollak, Michael N. Fuchs, Charles S. TI Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer SO CANCER RESEARCH LA English DT Article ID FACTOR-I RECEPTOR; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; C-PEPTIDE; BREAST-CANCER; FACTOR (IGF)-I; COLON-CANCER; MALE SMOKERS; WOMEN; GLUCOSE AB Insulin-like growth factor (IGF)-1 has growth-promoting effects on pancreatic cancer cells, and elevated fasting serum insulin has been linked to pancreatic cancer risk. IGF binding protein-1 (IGFBP-1) is a downstream target of insulin and inhibits IGF-I activity. To investigate whether prediagnostic plasma levels of IGFBP-1 are associated with pancreatic cancer risk, we did a prospective, case-control study nested within the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative. We assayed circulating IGFBP-1 among 144 pancreatic cancer cases that occurred 4 years after plasma collection and in 429 controls, matched for date of birth, prospective cohort, smoking status, and fasting status. When compared with participants in the three highest quartiles of plasma IGFBP-1, those in the lowest quartile experienced a relative risk (1111) for pancreatic cancer of 2.07 [95% confidence intervals (95% CI), 1.26-3.39], after adjusting for other risk factors, including circulating IGF-I, IGF binding protein-3, and C-peptide. Only participants in the lowest quartile of plasma IGFBP-1 showed an elevated risk of pancreatic cancer. The influence of low plasma IGFBP-1 became progressively stronger with time; among cases diagnosed >= 8 years after blood collection, the adjusted RR was 3.47 (95% Cl, 1.48-8.14), comparing the bottom versus the top three quartiles. The influence of plasma IGFBP- I was most marked among participants who never smoked cigarettes (1111, 3.30; 95% Cl, 1.48-7.35). Among participants in four U.S. prospective cohort studies, low plasma IGFBP-1 levels significantly predicted an increased risk of pancreatic cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Inst Translat Res Vienna, KFJ Spital & Appl Canc Res, Ludwig Boltzmann Inst Appl Canc, Vienna, Austria. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. McGill Univ, Montreal, PQ, Canada. Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ, Canada. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org RI Pollak, Michael/G-9094-2011; Michaud, Dominique/I-5231-2014 OI Pollak, Michael/0000-0003-3047-0604; FU NCI NIH HHS [CA55075, CA86102, CA87969, CA95589, R01 CA124908, T32 CA009172] NR 47 TC 40 Z9 41 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2007 VL 67 IS 16 BP 7923 EP 7928 DI 10.1158/0008-5472.CAN-07-0373 PG 6 WC Oncology SC Oncology GA 200XJ UT WOS:000248795800046 PM 17699799 ER PT J AU Ritter, CA Perez-Torres, M Rinehart, C Guix, M Dugger, T Engelman, JA Arteaga, CL AF Ritter, Christoph A. Perez-Torres, Marianela Rinehart, Cammie Guix, Marta Dugger, Teresa Engelman, Jeffrey A. Arteaga, Carlos L. TI Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB Ligands and remain dependent on the ErbB receptor network SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; HERCEPTIN-INDUCED INHIBITION; MONOCLONAL-ANTIBODY; DOWN-REGULATION; ADJUVANT CHEMOTHERAPY; EXTRACELLULAR DOMAIN; SIGNAL-TRANSDUCTION; LAPATINIB GW572016; FACTOR EGF; PHASE-I AB Purpose: We have investigated mechanisms of acquired resistance to the HER2 antibody trastuzumab in BT-474 human breast cancer cells. Experimental Design: BT-474 xenografts established in athymic nude mice were eliminated by trastuzumab. Continuous cell lines (HR for Herceptin resistant) were generated from tumors that recurred in the presence of continuous antibody therapy. Results: The isolated cells behaved resistant to trastuzumab in culture as well as when reinjected into nude mice. They retained HER2 gene amplification and trastuzumab binding and were exquisitely sensitive to peripheral blood mononuclear cells ex vivo in the presence of the antibody. The HR cells exhibited higher levels of phosphorylated epidermal growth factor receptor (EGFR) and EGFR/HER2 heterodimers. Phosphorylation of HER2 in HR cells was inhibited by the EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Gefitinib also inhibited the basal association of p85 with phosphorylated HER3 in HR cells. Both inhibitors as well as the dual EGFR/HER2 inhibitor, lapatinib, induced apoptosis of the HR cells in culture. Growth of established HR5 xenografts was inhibited by erlotinib in vivo. In addition, the HR cells overexpressed EGFR, transforming growth factor alpha, heparin-binding EGF, and heregulin RNAs compared with the parental trastuzumab-sensitive cells. Conclusions: These results are consistent with the inability of trastuzumab to block the heterodimerization of HER2 and suggest that amplification of ligand-induced activation of ErbB receptors is a plausible mechanism of acquired resistance to trastuzumab that should be investigated in primary mammary cancers. C1 Univ Greifswald, Inst Pharmacol, Greifswald, Germany. Univ Greifswald, Inst Pharm, Greifswald, Germany. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Dept Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Dept Canc Biol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program, Nashville, TN 37212 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Arteaga, CL (reprint author), Vanderbilt Univ, Med Ctr, Div Oncol, 2220 Pierce Ave,777PRB, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu FU NCI NIH HHS [CA78136, CA80195, P30 CA68485, P50 CA98131] NR 59 TC 282 Z9 290 U1 3 U2 18 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 AUG 15 PY 2007 VL 13 IS 16 BP 4909 EP 4919 DI 10.1158/1078-0432.CCR-07-0701 PG 11 WC Oncology SC Oncology GA 201ND UT WOS:000248837900034 PM 17699871 ER PT J AU Muller, FL Lustgarten, MS Jang, Y Richardson, A Van Remmen, H AF Muller, Florian L. Lustgarten, Michael S. Jang, Younginok Richardson, Arlan Van Remmen, Holly TI Trends in oxidative aging theories SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review ID MANGANESE-SUPEROXIDE-DISMUTASE; NEMATODE CAENORHABDITIS-ELEGANS; REPLICATIVE LIFE-SPAN; METHIONINE SULFOXIDE REDUCTASE; HUMAN-DIPLOID CELLS; BREAST-CANCER RISK; MITOCHONDRIAL RESPIRATORY-CHAIN; GENE-KNOCKOUT MICE; TRANSGENIC DROSOPHILA-MELANOGASTER; EARLY EMBRYONIC LETHALITY AB The early observations on the rate-of-living theory by Max Rubner and the report by Gershman that oxygen free radicals exist in vivo culminated in the seminal proposal in the 1950s by Denham Harman that reactive oxygen species are a cause of aging (free radical theory of aging). The goal of this review is to analyze recent findings relevant in evaluating Harman's theory using experimental results as grouped by model organisms (i.e., invertebrate models and mice). In this regard, we have focused primarily on recent work involving genetic manipulations. Because the free radical theory of aging is not the only theorem proposed to explain the mechanism(s) involved in aging at the molecular level, we also discuss how this theory is related to other areas of research in biogerontology, specifically, telomere/cell senescence, genomic instability, and the mitochondrial hypothesis of aging. We also discuss where we think the free radical theory is headed. It is now possible to give at least a partial answer to the question whether oxidative stress determines life span as Harman posed so long ago. Based on studies to date, we argue that a tentative case for oxidative stress as a life-span determinant can be made in Drosophila melanogaster. Studies in mice argue for a role of oxidative stress in age-related disease, especially cancer; however, with regard to aging per se, the data either do not support or remain inconclusive on whether oxidative stress determines life span. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Van Remmen, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu NR 368 TC 543 Z9 570 U1 12 U2 193 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 15 PY 2007 VL 43 IS 4 BP 477 EP 503 DI 10.1016/j.freeradbiomed.2007.03.034 PG 27 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 195HX UT WOS:000248404200001 PM 17640558 ER PT J AU Tomita, K Kubo, T Matsuda, K Fujiwara, T Yano, K Winograd, JM Tohyama, M Hosokawa, K AF Tomita, Koichi Kubo, Tateki Matsuda, Ken Fujiwara, Toshihiro Yano, Kenji Winograd, Jonathan M. Tohyama, Masaya Hosokawa, Ko TI The neurotrophin receptor p75(NTR) in Schwann cells is implicated in remyelination and motor recovery after peripheral nerve injury SO GLIA LA English DT Article DE p75(NTR) in Schwann cell; Schwann cell transplantation; peripheral nerve injury; remyelination; radial growth ID NF-KAPPA-B; SCIATIC-NERVE; CONDUCTION-VELOCITY; MYELIN FORMATION; GROWTH-FACTOR; P75; MICE; REGENERATION; SYSTEM; MIGRATION AB The function of the p75(NTR) neurotrophin receptor (p75(NTR)) in nervous system regeneration is still controversial. Part of that controversy may be due to the fact that p75(NTR) is expressed by both neuronal and glial cell types and may have very distinct and even contradictory roles in each population. In this study, to elucidate the in vivo function of p75(NTR) in Schwann cells during remyelination after peripheral nerve injury, we established a new animal model for p75(NTR)-deficient Schwann cell transplantation in nude mice. We performed quantitative assessments of the functional, histological, and electro physiological recovery after sciatic nerve injury, and compared them with those of the P75(NTR)(+1+) Schwann cell transplanted animals. At 710 weeks after injury, the motor recovery in the p75(NTR)(-/-) Schwann cell transplanted animals was significantly impaired compared with that in the p75(NTR)(+/+) Schwann cell transplanted animals. The lower number of the retrogradely labeled motoneurons and the hypomyelination in the p75(NTR)(-/-) Schwann cell transplanted animals were evident at 6 and 10 weeks after injury. At 10 weeks after injury, the radial growth in the axon caliber was also impaired in NTR the P75(NTR)(-/-) Schwann. cell transplanted animals. Measurement of the amount of myelin proteins and the nerve conduction velocity at 10 weeks after injury reflected these results. In summary, the p75(NTR) expression in Schwann cells is important for remyelination process, and the motor recovery after injury is impaired due to impaired axonal growth, remyelination, and radial growth in the axon calibers. (C) 2007 Wiley-Liss, Inc. C1 Osaka Univ, Grad Sch Med, Dept Plast Surg, Suita, Osaka 5650871, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. Osaka Univ, Grad Sch Med, Dept Anat & Neurosci, Osaka, Japan. RP Kubo, T (reprint author), Osaka Univ, Grad Sch Med, Dept Plast Surg, 2-2 Yamadaoka,C11, Suita, Osaka 5650871, Japan. EM tateki@psurg.med.osaka-u.ac.jp NR 39 TC 40 Z9 44 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD AUG 15 PY 2007 VL 55 IS 11 BP 1199 EP 1208 DI 10.1002/glia.20533 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 197RB UT WOS:000248572600010 PM 17600367 ER PT J AU Meyerhardt, JA Niedzwiecki, D Hollis, D Saltz, LB Hu, FB Mayer, RJ Nelson, H Whittom, R Hantel, A Thomas, J Fuchs, CS AF Meyerhardt, Jeffrey A. Niedzwiecki, Donna Hollis, Donna Saltz, Leonard B. Hu, Frank B. Mayer, Robert J. Nelson, Heidi Whittom, Renaud Hantel, Alexander Thomas, James Fuchs, Charles S. TI Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; TOTAL-ENERGY-INTAKE; IOWA WOMENS HEALTH; COLORECTAL-CANCER; MEAT CONSUMPTION; LIFE-STYLE; VITAMIN-D; PROSPECTIVE COHORT; PHYSICAL-ACTIVITY AB Context Dietary factors have been associated with the risk of developing colon cancer but the influence of diet on patients with established disease is unknown. Objective To determine the association of dietary patterns with cancer recurrences and mortality of colon cancer survivors. Design, Setting, and Patients Prospective observational study of 1009 patients with stage III colon cancer who were enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001. Patients reported on dietary intake using a semiquantitative food frequency questionnaire during and 6 months after adjuvant chemotherapy. We identified 2 major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was characterized by high intakes of fruits and vegetables, poultry, and fish; the Western pattern was characterized by high intakes of meat, fat, refined grains, and dessert. Patients were followed up for cancer recurrence or death. Main Outcome Measures Disease-free survival, recurrence-free survival, and overall survival by dietary pattern. Results During a median follow-up of 5.3 years for the overall cohort, 324 patients had cancer recurrence, 223 patients died with cancer recurrence, and 28 died without documented cancer recurrence. A higher intake of a Western dietary pattern after cancer diagnosis was associated with a significantly worse disease-free survival (colon cancer recurrences or death). Compared with patients in the lowest quintile of Western dietary pattern, those in the highest quintile experienced an adjusted hazard ratio (AHR) for disease-free survival of 3.25 (95% confidence interval [CI], 2.04-5.19; P for trend < .001). The Western dietary pattern was associated with a similar detriment in recurrence-free survival (AHR, 2.85; 95% CI, 1.75-4.63) and overall survival (AHR, 2.32; 95% CI, 1.36-3.96]), comparing highest to lowest quintiles (both with P for trend < .001). The reduction in disease-free survival with a Western dietary pattern was not significantly modified by sex, age, nodal stage, body mass index, physical activity level, baseline performance status, or treatment group. In contrast, the prudent dietary pattern was not significantly associated with cancer recurrence or mortality. Conclusions Higher intake of a Western dietary pattern may be associated with a higher risk of recurrence and mortality among patients with stage III colon cancer treated with surgery and adjuvant chemotherapy. Further studies are needed to delineate which components of such a diet show the strongest association. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Harvard Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Mayo Clin Fdn, Rochester, MN USA. Hop Sacre Coeur, Dept Med, Montreal, PQ H4J 1C5, Canada. Loyola Univ, Stritch Sch Med, Div Hematol & Oncol, Maywood, IL 60153 USA. Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org OI Saltz, Leonard/0000-0001-8353-4670 FU NCI NIH HHS [CA31946, CA33601, K07CA097992] NR 56 TC 163 Z9 169 U1 4 U2 8 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 AUG 15 PY 2007 VL 298 IS 7 BP 754 EP 764 DI 10.1001/jama.298.7.754 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 199XP UT WOS:000248728800020 PM 17699009 ER PT J AU Donahoe, SM Stewart, GC McCabe, CH Mohanavelu, S Murphy, SA Cannon, CP Antman, EM AF Donahoe, Sean M. Stewart, Garrick C. McCabe, Carolyn H. Mohanavelu, Satishkumar Murphy, Sabina A. Cannon, Christopher P. Antman, Elliott M. TI Diabetes and mortality following acute coronary syndromes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; AMERICAN-HEART-ASSOCIATION; TIMI RISK SCORE; CARDIOVASCULAR-DISEASES; FASTING GLUCOSE; INTRAVENOUS NPA; BLOOD-GLUCOSE; INTIME-II; TRIAL AB Context The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among persons with diabetes. The independent effect of diabetes on mortality following acute coronary syndromes (ACS) is uncertain. Objective To evaluate the influence of diabetes on mortality following ACS using a large database spanning the full spectrum of ACS. Design, Setting, and Patients A subgroup analysis of patients with diabetes enrolled in randomized clinical trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62 036 patients (46 577 with ST-segment elevation myocardial infarction [STEMI] and 15 459 with unstable angina/non-STEMI [UA/NSTEMI]), of whom 10 613 (17.1%) had diabetes. A multivariable model was constructed to adjust for baseline characteristics, aspects of ACS presentation, and treatments for the ACS event. Main Outcome Measures Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes. Results Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI (2.1% vs 1.1%, P < .001) and STEMI (8.5% vs 5.4%, P < .001). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with higher 30-day mortality after UA/NSTEMI (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.24-2.56) or STEMI (OR, 1.40; 95% CI, 1.24-1.57). Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI (hazard ratio [HR], 1.65; 95% CI, 1.30-2.10) or STEMI (HR, 1.22; 95% CI, 1.08-1.38). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2% vs 8.1%). Conclusion Despite modern therapies for ACS, diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Cornell Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10021 USA. RP Antman, EM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, 75 Francis St, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu NR 49 TC 290 Z9 308 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 15 PY 2007 VL 298 IS 7 BP 765 EP 775 DI 10.1001/jama.298.7.765 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 199XP UT WOS:000248728800021 PM 17699010 ER PT J AU Cho, E Willett, WC Colditz, GA Fuchs, CS Wu, K Chan, AT Zeisel, SH Giovannucci, EL AF Cho, Eunyoung Willett, Walter C. Colditz, Graham A. Fuchs, Charles S. Wu, Kana Chan, Andrew T. Zeisel, Steven H. Giovannucci, Edward L. TI Dietary choline and betaine and the risk of distal colorectal adenoma in women SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PLASMA HOMOCYSTEINE CONCENTRATIONS; MALIGNANT-TRANSFORMATION; EPITHELIAL-CELLS; KINASE-ACTIVITY; COLON-CANCER; HEALTHY-MEN; DEVOID DIET; FOLATE; METHIONINE; NUTRIENT AB Background Choline and betaine are involved in methyl-group metabolism as methyl-group donors; thus, like folate, another methyl-group donor, they may be associated with a reduced risk of colorectal adenomas. No epidemiologic study has examined the association of intake of these nutrients and colorectal adenoma risk. Methods We investigated the relationship between intakes of choline and betaine and risk of colorectal adenoma in US women enrolled in the Nurses' Health Study. Dietary intake was measured by food-frequency questionnaires, and individual intakes of choline and betaine were calculated by multiplying the frequency of consumption of each food item by its choline and betaine content and summing the nutrient contributions of all foods. Logistic regression models were used to calculate adjusted odds ratios (as approximations for relative risks) and 95% confidence intervals (CIs) of colorectal adenoma. All statistical tests were two-sided. Results Among 39246 women who were initially free of cancer or polyps and who had at least one endoscopy from 1984 through 2002, 2408 adenoma cases were documented. Increasing choline intake was associated with an elevated risk of colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake, relative to the lowest quintile, were 1.03 (0.90 to 1.18), 1.01 (0.88 to 1.16), 1.23 (1.07 to 1.41), and 1.45 (1.27 to 1.67; P-trend <.001). Betaine intake had a nonlinear inverse association with colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake were 0.94 (0.83 to 1.07), 0.85 (0.75 to 0.97), 0.86 (0.75 to 0.98), and 0.90 (95% CI = 0.78 to 1.04; P-trend = .09). Among individual sources of choline, choline from phosphatidylcholine and from sphingomyelin were each positively related to adenoma risk. Conclusions Our findings do not support an inverse association between choline intake and risk of colorectal adenoma. The positive association between choline intake and colorectal adenoma that we observed could represent effects of other components in the foods from which choline was derived and should be investigated further. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP Cho, E (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA108341, CA87969, P01 CA087969, R03 CA108341]; NIDDK NIH HHS [P30 DK040561, DK55865, DK56350, P30 DK040561-12, P30 DK056350, P30 DK056350-08, R01 DK055865, R01 DK055865-07] NR 36 TC 54 Z9 57 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD AUG 15 PY 2007 VL 99 IS 16 BP 1224 EP 1231 DI 10.1093/jnci/djm082 PG 8 WC Oncology SC Oncology GA 204PD UT WOS:000249055600006 PM 17686825 ER PT J AU Dunn, IS Haggerty, TJ Kono, M Durda, PJ Butera, D Macdonald, DB Benson, EM Rose, LB Kurnick, JT AF Dunn, Ian S. Haggerty, Timothy J. Kono, Michihiro Durda, Paul J. Butera, David Macdonald, David B. Benson, Elizabeth M. Rose, Lenora B. Kurnick, James T. TI Enhancement of human melanoma antigen expression by IFN-beta SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALPHA/BETA-RECEPTOR INTERACTIONS; RECOMBINANT HUMAN-LEUKOCYTE; CYTOTOXIC T-CELLS; INTERFERON-BETA; I INTERFERONS; GENE-THERAPY; DIFFERENTIATION PROTEINS; FIBROBLAST INTERFERON; MALIGNANT-MELANOMA; HUMAN GLIOBLASTOMA AB Although many immunotherapeutic investigations have focused on improving the effector limb of the antitumor response, few studies have addressed preventing the loss of tumor-associated Ag (TAA) expression, associated with immune escape by tumors. We found that TAA loss from human melanomas usually results from reversible gene down-regulation, rather than gene deletion or mutation. Previously, we showed that inhibitors of MAPK-signaling pathways up-regulate TAA expression in melanoma cell lines. We have now identified IFN-beta as an additional stimulus to TAA expression, including Melan-A/MART-1, gp100, and MAGE-Al. IFN-beta (but neither IFN-alpha nor IFN-gamma) augmented both protein and mRNA expression of melanocytic TAA in 15 melanoma lines (irrespective of initial Ag-expression levels). Treatment of low Ag melanoma lines with IFN-beta increased expression of melanocyte-lineage Ags, inducing susceptibility to lysis by specific CTLs. Treatment with IFN-beta also enhances expression of class I HLA molecules, thereby inducing both nominal TAA and the presenting HLA molecule. Data from fluorescent cellular reporter systems demonstrated that IIFN-beta triggers promoter activation, resulting in augmentation of Ag expression. In addition to enhancing TAA expression in melanomas, IFN-beta also stimulated expression of the melanocytic Ag gp100 in cells of other neural crest-derived tumor lines (gliomas) and certain unrelated tumors. Because IFN-beta is already approved for human clinical use in other contexts, it may prove useful as a cotreatment for augmenting tumor Ag expression during immunotherapy. C1 CytoCure, Beverly, MA 01915 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Westmead Hosp, Dept Immunopathol, Sydney, NSW, Australia. RP Kurnick, JT (reprint author), CytoCure, 100 Cummings Ctr,Suite 430, Beverly, MA 01915 USA. EM kurnick@massmed.org RI Kono, Michihiro/I-1238-2012 OI Kono, Michihiro/0000-0003-2639-1583 FU NCI NIH HHS [R43-CA86153, R43-CA94700, R43-CA96271] NR 54 TC 12 Z9 14 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2007 VL 179 IS 4 BP 2134 EP 2142 PG 9 WC Immunology SC Immunology GA 203EZ UT WOS:000248959200015 PM 17675472 ER PT J AU Cariappa, A Boboila, C Moran, ST Liu, HY Shi, HN Pillai, S AF Cariappa, Annaiah Boboila, Cristian Moran, Stewart T. Liu, Haoyuan Shi, Hai Ning Pillai, Shiv TI The recirculating B cell pool contains two functionally distinct, long-lived, posttransitional, follicular B cell Populations SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAT-STABLE ANTIGEN(HI); MARGINAL-ZONE; POSITIVE SELECTION; T-CELLS; FATE SPECIFICATION; BONE-MARROW; B1B CELLS; MICE; LYMPHOCYTES; MATURATION AB Disparate models for the development of peripheral B cells may reflect significant heterogeneity in recirculating long-lived B cells that have not been previously accounted for. We show in this study that the murine recirculating B cell pool contains two distinct, long-lived, posttransitional, follicular B cell populations. Follicular Type I IgM(low) B cells require Ag-derived and Btk-dependent signals for their development and make up the majority of cells in the recirculating follicular B cell pool. Follicular type II B cells do not require Btk- or Notch-2-derived signals, make up about a third of the long-lived recirculating B cell pool, and can develop in the absence of Ag. These two follicular populations exhibit differences in basal tyrosine phosphorylation and in BCR-induced proliferation, suggesting that they may represent functionally distinct populations of long-lived recirculating B cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NCI NIH HHS [CA102793]; NIAID NIH HHS [AI06493] NR 56 TC 41 Z9 41 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2007 VL 179 IS 4 BP 2270 EP 2281 PG 12 WC Immunology SC Immunology GA 203EZ UT WOS:000248959200031 PM 17675488 ER PT J AU Xu, C Sui, X Tao, H Zhu, Q Marasco, WA AF Xu, Chen Sui, Xanhua Tao, Hong Zhu, Quan Marasco, Wayne A. TI Human Anti-CXCR4 antibodies undergo V-H replacement, exhibit functional V-region sulfation, and define CXCR4 antigenic heterogeneity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CXCR4; STEM-CELL MOBILIZATION; N-LINKED GLYCOSYLATION; TYROSINE SULFATION; STROMAL CELLS; BONE-MARROW; PARAMAGNETIC PROTEOLIPOSOMES; PATHFINDER SELECTION; CORECEPTOR FUNCTION AB The chemokine receptor CXCR4 and its ligand stromal-derived factor-1 (SDF-1/CXCL12) are essential for many biological processes and various pathological conditions. However, the relationship between CXCR4 antigenic structure and SDF-1-mediated biological responses is poorly understood. In this report, a panel of human anti-CXCR4 Abs were isolated and used to explore CXCR4 antigenic heterogeneity and function. Multiple fixed CXCR4 antigenic isoforms were detected on the surface of hemopoietic cells. Epitope mapping studies demonstrated the complex nature of the surface-exposed CXCR4 epitopes. Ab-mediated inhibition of chemotaxis correlated strongly with binding affinity, epitope recognition, as well as the level of CXCR4 isoform expression. In addition, detailed genetic analyses of these Abs showed evidence of V, replacement. Importantly, structural and biochemical studies demonstrated tyrosine sulfation in novel regions of the V genes that contributed bidirectionally to the binding activity of the Abs. These data provide the first evidence that functional tyrosine sulfation occurs in self-reactive Abs and suggest a potential new mechanism that may contribute to the pathogenesis of Ab-mediated autoimmune disease. These Abs also provide valuable tools to explore the selective in vivo targeting of CXCR4 isoforms that may be preferentially expressed in certain disease states and involved in steady-state CXCR4-SDF-1 homeostasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.ed FU NIAID NIH HHS [AI52829, AI58804, AI060456] NR 67 TC 13 Z9 14 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2007 VL 179 IS 4 BP 2408 EP 2418 PG 11 WC Immunology SC Immunology GA 203EZ UT WOS:000248959200045 PM 17675502 ER PT J AU Blanc, FX Havlir, DV Onyebujoh, PC Thim, S Goldfeld, AE Delfraissy, JF AF Blanc, Francois-Xavier Havlir, Diane V. Onyebujoh, Philip C. Thim, Sok Goldfeld, Anne E. Delfraissy, Jean-Francois TI Treatment strategies for HIV-infected patients with tuberculosis: Ongoing and planned clinical trials SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; MANAGEMENT; SETTINGS; CAMBODIA; ADULTS AB Currently, there are limited data to guide the management of highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 (HIV-1)-infected patients with active tuberculosis (TB), the leading cause of death among individuals with acquired immunodeficiency syndrome (AIDS) in resource-limited areas. Four trials to take place in Southeast Asian, African, and South American countries will address the unresolved question of the optimal timing for initiation of HAART in patients with AIDS and TB: (1) Cambodian Early versus Late Introduction of Antiretrovirals (CAMELIA [ANRS 1295/NIH-CIPRA KH001]), (2) Adult AIDS Clinical Trials Group A5221, (3) START, and (4) a trial sponsored by the World Health Organization/Special Programme for Research and Training in Tropical Diseases. Two other clinical questions regarding patients with TB and HIV-1 coinfection are also undergoing evaluation: (1) the benefits of short-term HAART when CD4 cell counts are 1350 cells/mm3 (PART [NIH 1 R01 AI051219-01A2]) and (2) the efficacy of a once-daily HAART regimen in treatment-naive patients (BKVIR [ANRS 129]). Here, we present an overview of these ongoing or planned clinical studies, which are supported by international agencies. C1 Univ Paris 11, CHU Bicetre, AP HP, Serv Med Interne, F-94275 Le Kremlin Bicetre, France. Univ Paris 11, CHU Bicetre, AP HP, Agence Natl Rech Sida & Hepatites Virales, F-94275 Le Kremlin Bicetre, France. Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. WHO, United Nat Childrens Fund, United Nat Dev Programme, Worl Bank,Special Programme Res & Training Trop D, CH-1211 Geneva, Switzerland. Cambodian Hlth Comm, Phnom Penh, Cambodia. RP Blanc, FX (reprint author), Univ Paris 11, CHU Bicetre, AP HP, Serv Med Interne, 78 Rue Gen Leclerc, F-94275 Le Kremlin Bicetre, France. EM xavier.blanc@bct.aphp.fr RI Blanc, Francois-Xavier/D-7425-2015 NR 21 TC 36 Z9 37 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2007 VL 196 SU 1 BP S46 EP S51 DI 10.1086/518658 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190GC UT WOS:000248045700007 PM 17624825 ER PT J AU Kosinski, CM Schlangen, C Gellerich, FN Gizatullina, Z Deschauer, M Schiefer, J Young, AB Landwehrmeyer, GB Toyka, KV Sellhaus, B Lindenberg, KS AF Kosinski, Christoph M. Schlangen, Christiane Gellerich, Frank N. Gizatullina, Zemfira Deschauer, Markus Schiefer, Johannes Young, Anne B. Landwehrmeyer, Georg Bernhard Toyka, Klaus V. Sellhaus, Bernd Lindenberg, Katrin S. TI Myopathy as a first symptom of Huntington's disease in a marathon runner SO MOVEMENT DISORDERS LA English DT Article DE neurodegenerative disease; oxidative stress; mitochondrial; disease ID SKELETAL-MUSCLE; ENERGY-METABOLISM; TRANSGENIC MICE; MUTATION AB A semi professional marathon runner at risk for Huntington's disease (HD) (43 CAG repeats) developed signs of a slowly progressive myopathy with exercise-induced muscle fatigue, pain, elevated creatine kinase level, and worsening of his running performance many years before first signs of chorea were detected. Muscle biopsy displayed a mild myopathy with mitochondrial pathology including a complex IV deficiency and analysis of the patient's fibroblast culture demonstrated deficits in mitochondrial function. Challenging skeletal muscle by excessive training might have disclosed myopathy in HD even years before the appearance of other neurological symptoms. (c) 2007 Movement Disorder Society. C1 Univ Hosp RWTH Aachen, Dept Neurol, Inst Neuropathol, Aachen, Germany. KeyNeurotek Pharmaceut AG, Magdeburg, Germany. Univ Halle Wittenberg, Dept Neurol, Halle, Germany. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis MIND, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. Univ Wurzburg, Dept Neurol, D-8700 Wurzburg, Germany. RP Kosinski, CM (reprint author), Pauwelsstr 30, D-52074 Aachen, Germany. EM ckosinski@ukaachen.de OI Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X NR 15 TC 36 Z9 36 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG 15 PY 2007 VL 22 IS 11 BP 1637 EP 1640 DI 10.1002/mds.21550 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 207CI UT WOS:000249228800019 PM 17534945 ER PT J AU Papapetropoulos, S Friedman, J Blackstone, C Kleiner, GI Bowen, BC Singer, C AF Papapetropoulos, Spiridon Friedman, Jennifer Blackstone, Craig Kleiner, Gary I. Bowen, Brian C. Singer, Carlos TI A progressive, fatal dystonia-parkinsonism syndrome in a patient with primary immunodeficiency receiving chronic IVIG therapy SO MOVEMENT DISORDERS LA English DT Article DE extrapyramidal syndrome; dystonia; IVIG; X-linked agammaglobulinemia ID X-LINKED AGAMMAGLOBULINEMIA; INTRAVENOUS IMMUNOGLOBULIN; BRAIN IRON; GENE; NEURODEGENERATION; PROTEIN AB !fX-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by a mutation in the Bruton agammaglobulinemia tyrosine kinase gene that results in severe B-cell deficiency. So far, neurological complications of XLA have been primarily related to acute and/or chronic central nervous system enteroviral infections. In the last few years a progressive neurodegenerative syndrome of unknown etiology has been described in XLA patients. We describe and present a video of an XLA patient who developed a fatal dementing, dystonia-Parkinsonism syndrome 14 years into his immune disorder. Physician awareness of this rare syndrome may lead to its better characterization and management. (C) 2007 Movement Disorder Society. C1 Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Rady Childrens Hosp, Dept Neurol, San Diego, CA USA. Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, NIH, Bethesda, MD USA. Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33152 USA. Univ Miami, Miller Sch Med, Dept Radiol, Miami, FL 33152 USA. RP Papapetropoulos, S (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, 1501 NW 9th Ave NPF,Room 4004, Miami, FL 33136 USA. EM spapapetropoulos@med.miami.edu NR 14 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG 15 PY 2007 VL 22 IS 11 BP 1664 EP 1666 DI 10.1002/mds.21631 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 207CI UT WOS:000249228800027 PM 17588239 ER PT J AU Manoach, DS Ketwaroo, GA Polli, FE Thakkar, KN Barton, JJS Goff, DC Fischl, B Vangel, M Tuch, DS AF Manoach, Dara S. Ketwaroo, G. Avinash Polli, Frida E. Thakkar, Katharine N. Barton, Jason J. S. Goff, Donald C. Fischl, Bruce Vangel, Mark Tuch, David S. TI Reduced microstructural integrity of the white matter underlying anterior cingulate cortex is associated with increased saccadic latency in schizophrenia SO NEUROIMAGE LA English DT Review DE anterior cingulate cortex; antisaccade; cingulum bundle; diffusion tensor imaging; schizophrenia; white matter ID DIFFUSION TENSOR MRI; FRONTAL EYE-FIELD; POSITRON EMISSION TOMOGRAPHY; CHOICE-REACTION TIME; EVENT-RELATED FMRI; 1ST-EPISODE SCHIZOPHRENIA; COORDINATE SYSTEM; CEREBRAL-CORTEX; CORTICAL SURFACE; COUNTING STROOP AB The anterior cingulate cortex (ACC) is a key component of a network that directs both spatial attention and saccadic eye movements, which are tightly linked. Diffusion tensor imaging (DTI) has demonstrated reduced microstructural integrity of the anterior cingulum bundle as indexed by fractional anisotropy (FA) in schizophrenia, but the functional significance of these abnormalities is unclear. Using DTI, we examined the white matter underlying anterior cingulate cortex in schizophrenia to determine whether reduced FA is associated with prolonged latencies of volitional saccades. Seventeen chronic, medicated schizophrenia outpatients and nineteen healthy controls had high-resolution DTI scans. FA maps were registered to structural scans and mapped across participants using a surface-based coordinate system. Cingulate white matter was divided into rostral and dorsal anterior regions and a posterior region. Patients showed reduced FA in cingulate white matter of the right hemisphere. Reduced FA in the white matter underlying anterior cingulate cortex, frontal eye field, and posterior parietal cortex of the right hemisphere was associated with longer saccadic latencies in schizophrenia, though given the relatively small sample size, these relations warrant replication. These findings demonstrate that in schizophrenia, increased latency of volitional saccades is associated with reduced microstructural integrity of the white matter underlying key cortical components of a right-hemisphere dominant network for visuospatial attention and ocular motor control. Moreover, they suggest that anterior cingulate white matter abnormalities contribute to slower performance of volitional saccades and to inter-individual variability of saccadic latency in chronic, medicated schizophrenia. (c) 2007 Published by Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02215 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. Univ British Columbia, Dept Neurol, Vancouver, BC, Canada. Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC, Canada. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, 36 First Ave,Room 420, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; OI Thakkar, Katharine/0000-0002-0026-2030 FU NCRR NIH HHS [U24 RR021382, R01 RR16594-01A1, P41 RR14075]; NIBIB NIH HHS [R01 EB001550, U54 EB005149]; PHS HHS [BIRN002, P01 31154, R01 67720, R01 31340] NR 106 TC 41 Z9 42 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2007 VL 37 IS 2 BP 599 EP 610 DI 10.1016/j.neuroimage.2007.04.062 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 197VU UT WOS:000248585400023 PM 17590354 ER PT J AU Knake, S Wang, CM Ulbert, I Schomer, DL Halgren, E AF Knake, Susanne Wang, Chun Mao Ulbert, Istvan Schomer, Donald L. Halgren, Eric TI Specific increase of human entorhinal population synaptic and neuronal activity during retrieval SO NEUROIMAGE LA English DT Article ID HUMAN HIPPOCAMPAL FORMATION; MEDIAL TEMPORAL-LOBE; MEMORY CONSOLIDATION; DECLARATIVE MEMORY; PROCESSING STAGES; CORTEX; STIMULATION; RECOGNITION; FAMILIARITY; POTENTIALS AB Population transmembrane currents and neuronal firing in different layers of the human entorhinal cortex (ER) were recorded during semantic and episodic memory processes using a linear array of 24 laminar microelectrodes. Both measures, as well as local broadband spectral power, increased during retrieval of newly-learned character istics, especially in superficial layers. No differences were observed in the activity evoked by remembering people as compared to places Semantic retrieval evoked similar activity. In contrast, intentional encoding of declarative memory evoked relatively little activity. it double-dissociation of these responses with simultaneously recorded lateral inferotemporal recordings suggests that entorhinal cortex may be specifically engaged during retrieval, across multiple memory types and materials. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Univ Marburg, Dept Neurol, Marburg, Germany. Hungarian Acad Sci, Dept Psychol, Budapest, Hungary. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. NYU, Sch Med, Comprehens Epilepsy Ctr, New York, NY 10016 USA. Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci & Psychiat, Multimodal Imaging Lab, La Jolla, CA 92093 USA. RP Halgren, E (reprint author), 9500 Gilman Dr,Mail Code 0841, La Jolla, CA 92093 USA. EM ehalgren@ucsd.edu RI Ulbert, Istvan/F-2213-2010 FU NINDS NIH HHS [NS44623, NS18741, R01 NS018741-23A1, R01 NS018741, R01 NS044623, R01 NS044623-05] NR 30 TC 8 Z9 10 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2007 VL 37 IS 2 BP 618 EP 622 DI 10.1016/j.neuroimage.2007.05.009 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 197VU UT WOS:000248585400025 PM 17566769 ER PT J AU Joo, CM de Boer, JF AF Joo, Chulmin de Boer, Johannes F. TI Spectral-domain optical coherence reflectometric sensor for highly sensitive molecular detection SO OPTICS LETTERS LA English DT Article ID PHASE MICROSCOPY; TOMOGRAPHY AB We describe what we believe to be a novel use of spectral-domain optical coherence reflectometry (SD-OCR) for highly sensitive molecular detection in real time. The SD-OCR sensor allows identification of a sensor surface of interest in an OCR depth scan and monitoring the phase alteration due to molecular interaction at that surface with subnanometer optical thickness sensitivity. We present subfemtomole detection sensitivity for etching of SiO2 molecules and demonstrate its application as a biosensor by measuring biotinstreptavidin binding in a microfluidic device. (C) 2007 Optical Society of America. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP de Boer, JF (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976 FU NCRR NIH HHS [R01 RR 19768]; NEI NIH HHS [EY 14975] NR 18 TC 9 Z9 10 U1 0 U2 4 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 AUG 15 PY 2007 VL 32 IS 16 BP 2426 EP 2428 DI 10.1364/OL.32.002426 PG 3 WC Optics SC Optics GA 208NX UT WOS:000249327600052 PM 17700807 ER PT J AU Figlewicz, DP Naleid, AM Sipols, AJ AF Figlewicz, Dianne P. Naleid, Amy MacDonald Sipols, Alfred J. TI Modulation of food reward by adiposity signals SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE insulin; leptin; ventral tegmental area; dopamine; self-administration ID CONDITIONED PLACE PREFERENCE; DOPAMINE TRANSPORTER; INTRAVENTRICULAR INSULIN; NUCLEUS-ACCUMBENS; PHOSPHATIDYLINOSITOL 3-KINASE; MOTIVATED BEHAVIOR; SUCROSE SOLUTIONS; SELF-STIMULATION; ARCUATE NUCLEUS; MESSENGER-RNA AB Extensive historical evidence from the drug abuse literature has provided support for the concept that there is functional communication between central nervous system (CNS) circuitries which subserve reward/motivation, and the regulation of energy homeostasis. This concept is substantiated by recent studies that map anatomical pathways, or which demonstrate that hormones and neurotransmitters associated with energy homeostasis regulation can directly modulate reward and motivation behaviors. Studies from our laboratory have focused specifically on the candidate adiposity hormones, insulin and leptin, and show that these hormones can decrease performance in behavioral paradigms that assess the rewarding or motivating properties of food. Additionally we and others have provided evidence that the ventral tegmental area may be one direct target for these effects, and we are currently exploring other potential anatomical targets. Finally, we are beginning to explore the interaction between adiposity signals, chronic maintenance diet of rats, and different types of food rewards to more closely simulate the current food environments of Westernized societies including the U.S. We propose that future studies of food reward should include a more complex environment in the experimental design that takes into account abundance and variety of rewarding foods, psychological stressors, and choices of reward modalities. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Latvia, Inst Expt & Clin Med, Riga, Latvia. VA Puget Sound Hlth Care Syst 151, Seattle, WA 98108 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU NCRR NIH HHS [P20 RR020774, 5 P20 RR020774]; NIAAA NIH HHS [T32 AA007455]; NIDDK NIH HHS [R01 DK040963-18, R01 DK040963, R01 DK40963, R01 DK040963-19, R01 DK040963-20] NR 56 TC 79 Z9 80 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD AUG 15 PY 2007 VL 91 IS 5 BP 473 EP 478 DI 10.1016/j.physbeh.2006.10.008 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 217JR UT WOS:000249944700002 PM 17137609 ER PT J AU Minzenberg, MJ Fan, J New, AS Tang, CY Siever, LJ AF Minzenberg, Michael J. Fan, Jin New, Antonia S. Tang, Cheuk Y. Siever, Larry J. TI Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: An event-related fMRI study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE anterior cingulate cortex; amygdala; fear; anger; functional magnetic resonance imaging ID POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; NEURAL RESPONSES; IMPULSIVE AGGRESSION; HEALTHY-VOLUNTEERS; BASAL FOREBRAIN; CHILDHOOD ABUSE; AMYGDALA VOLUME; FEMALE-PATIENTS; FEARFUL FACES AB Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of fronto-limbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HQ viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HQ in the bilateral rostral/ subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/ subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. RP Minzenberg, MJ (reprint author), UC Davis Hlth Syst, Imaging Res Ctr, 4701 X St, Sacramento, CA 95817 USA. EM michael.minzenberg@ucdmc.ucdavis.edu RI Fan, Jin/A-6716-2009 OI Fan, Jin/0000-0001-9630-8330 FU NCRR NIH HHS [M01 RR000071, M01 RR00071]; NIMH NIH HHS [R01 MH067918, R01 MH067918-01A1] NR 83 TC 133 Z9 135 U1 7 U2 23 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 AUG 15 PY 2007 VL 155 IS 3 BP 231 EP 243 DI 10.1016/j.pseychresns.2007.03.006 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 203JV UT WOS:000248971800006 PM 17601709 ER PT J AU Atlas, SJ Tosteson, TD Hanscom, B Blood, EA Pransky, GS Abdu, MWA Andersson, GB Weinstein, JN AF Atlas, Steven J. Tosteson, Tor D. Hanscom, Brett Blood, Emily A. Pransky, Glenn S. Abdu, William A. Andersson, Gunnar B. Weinstein, James N. TI What is different about worker's compensation patients? - Socioeconomic predictors of baseline disability status among patients with lumbar radiculopathy SO SPINE LA English DT Article DE workers' compensation; disability; lumbar disc herniation; sciatica; spinal stenosis; predictors ID LOW-BACK-PAIN; RESEARCH TRIAL SPORT; RETURN-TO-WORK; NONOPERATIVE TREATMENT; SURGICAL-TREATMENT; DISK HERNIATION; SECONDARY GAIN; RISK-FACTORS; OUTCOMES; SURGERY AB Study Design. Combined analysis of 2 prospective clinical studies. Objective. To identify socioeconomic characteristics associated with workers' compensation in patients with an intervertebral disc herniation (IDH) or spinal stenosis (SpS). Summary of Background Data. Few studies have compared socioeconomic differences between those receiving or not receiving workers' compensation with the same underlying clinical conditions. Methods. Patients were identified from the Spine Patient Outcomes Research Trial ( SPORT) and the National Spine Network (NSN) practice-based outcomes study. Patients with IDH and SpS within NSN were identified satisfying SPORT eligibility criteria. Information on disability and work status at baseline evaluation was used to categorize patients into 3 groups: workers' compensation, other disability compensation, or work-eligible controls. Enrollment rates of patients with disability in a clinical efficacy trial ( SPORT) and practice-based network ( NSN) were compared. Independent socioeconomic predictors of baseline workers' compensation status were identified in multivariate logistic regression models controlling for clinical condition, study cohort, and initial treatment designation. Results. Among 3759 eligible patients ( 1480 in SPORT and 2279 in NSN), 564 (15%) were receiving workers' compensation, 317 (8%) were receiving other disability compensation, and 2878 (77%) were controls. Patients receiving workers' compensation were less common in SPORT than NSN (9.2% vs. 18.8%, P < 0.001), but patients receiving other disability compensation were similarly represented (8.9% vs. 7.7%, P = 0.19). In univariate analyses, many socioeconomic characteristics significantly differed according to baseline workers' compensation status. In multiple logistic regression analyses, gender, educational level, work characteristics, legal action, and expectations about ability to work without surgery were independently associated with receiving workers' compensation. Conclusion. Clinical trials involving conditions commonly seen in patients with workers' compensation may need special efforts to ensure adequate representation. Socioeconomic characteristics markedly differed between patients receiving and not receiving workers' compensation. Identifying the independent effects of workers' compensation on outcomes will require controlling for these baseline characteristics and other clinical features associated with disability status. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, Boston, MA 02114 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Liberty Mutual Ctr Disabil Res, Hopkinton, MA USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org FU NCI NIH HHS [P30 CA023108]; NIAMS NIH HHS [P60 AR048094, P60 AR048094-05, U01 AR045444, U01 AR045444-07, U01-AR45444] NR 36 TC 16 Z9 16 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD AUG 15 PY 2007 VL 32 IS 18 BP 2019 EP 2026 DI 10.1097/BRS.0b013e318133d69b PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 201CT UT WOS:000248809800015 PM 17700451 ER PT J AU Greenberg, B Thomas, I Banish, D Goldman, S Havranek, E Massie, BM Zhu, Y Ticho, B Abraham, WT AF Greenberg, Barry Thomas, Ignatius Banish, Dorothy Goldman, Steven Havranek, Edward Massie, Barry M. Zhu, Ying Ticho, Barry Abraham, William T. TI Effects of multiple oral doses of an A(1) adenosine antagonist, BG9928, in patients with heart failure - Results of a placebo-controlled, dose-escalation study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID WORSENING RENAL-FUNCTION; RECEPTOR ANTAGONIST; BG9719 CVT-124; DYSFUNCTION; THERAPY; IMPACT AB Objectives This study sought to assess the pharmacokinetics and clinical effects of oral BG9928 in heart failure (HF) patients. Background Declining renal function during HF treatment is associated with poor outcomes. BG9928, a selective inhibitor of the Al adenosine receptor, is proposed to cause natriuresis without causing a decline in renal function. Methods A randomized, double-blind, placebo-controlled study was conducted in patients with HF and systolic dysfunction who were receiving standard therapy. Patients were randomized to receive BG9928 (3, 15, 75, or 225 mg) or placebo orally for 10 days. The primary end point was change in sodium excretion. Changes in potassium excretion, creatinine clearance, and body weight also were evaluated. Results A total of 50 patients were studied. BG9928 increased sodium excretion compared with placebo, and natriuresis was maintained over 10 days with little kaliuresis. A linear trend in dose response was observed on day 1 (p = 0.04) but not on days 6 or 10. Adjusted creatinine clearance was unchanged over the 10 days. Patients who received 15, 75, or 225 mg of BG9928 had a reduction in body weight compared with placebo (-0.6, -0.7, -0.5, vs. +0.3 kg, respectively) at the end of study. BG9928 was well tolerated. The pharmacokinetic profile of BG9928 was consistent with once-daily dosing. Conclusions Oral BG9928 over the dose range of 3 to 225 mg/day produced significant increases in sodium excretion in patients with stable HF without causing kaliuresis or reducing renal function. (J Am Coll Cardiol 2007;50:600-6) (c) 2007 by the American College of Cardiology Foundation. C1 Univ Calif San Diego, Adv Heart Failure Treatment Program, San Diego, CA 92103 USA. Med Res Inst, Louisville, KY USA. Tchefunctr Cardiovasc Assoc, Louisville, KY USA. Tucson VA Med Ctr, SACAHCS, Sarver Heart Ctr, Tucson, AZ USA. Univ Tucson, Tucson, AZ USA. Denver Med Ctr, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Biogen Idec Inc, Cambridge, MA USA. Ohio State Univ, Heart Ctr, Div Cardiol, Columbus, OH 43210 USA. RP Greenberg, B (reprint author), Univ Calif San Diego, Adv Heart Failure Treatment Program, 200 W Arbor Dr 8411, San Diego, CA 92103 USA. EM bgreenberg@ucsd.edu NR 15 TC 42 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 14 PY 2007 VL 50 IS 7 BP 600 EP 606 DI 10.1016/j.jacc.2007.03.059 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 204MY UT WOS:000249049300006 PM 17692744 ER PT J AU Januzzi, JL Peacock, WF Maisel, AS Chae, CU Jesse, RL Baggish, AL O'Donoghue, M Sakhuja, R Chen, AA van Kimmenade, RRJ Lewandrowski, KB Lloyd-Jones, DM Wu, AHB AF Januzzi, James L., Jr. Peacock, W. Frank Maisel, Alan S. Chae, Claudia U. Jesse, Robert L. Baggish, Aaron L. O'Donoghue, Michelle Sakhuja, Rahul Chen, Annabel A. van Kimmenade, Roland R. J. Lewandrowski, Kent B. Lloyd-Jones, Donald M. Wu, Alan H. B. TI Measurement of the interleukin family member ST2 in patients with acute dyspnea SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NATRIURETIC PEPTIDE; SOLUBLE ST2; RESPONSE GENE; EMERGENCY-DEPARTMENT; ACUTE EXACERBATION; HEART-FAILURE; PROTEIN; RECEPTOR; SERUM; EXPRESSION AB Objectives The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. Background Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). Methods Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. Results Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration >= 0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [Cl] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% Cl 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value < 0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. Conclusions Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP. (J Am Coll Cardiol 2007;50:607-13) (c) 2007 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Dept Med & Lab Med, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Emergency Med, Cleveland, OH 44195 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med & Lab Med, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org RI Lloyd-Jones, Donald/C-5899-2009; Kimmenade, R.R.J./L-4432-2015 NR 27 TC 189 Z9 196 U1 0 U2 4 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 AUG 14 PY 2007 VL 50 IS 7 BP 607 EP 613 DI 10.1016/j.jacc.2007.05.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 204MY UT WOS:000249049300007 PM 17692745 ER PT J AU Li, G Sokal, I Quinn, JF Leverenz, JB Brodey, M Schellenberg, GD Kaye, JA Raskind, MA Zhang, J Peskind, ER Montine, TJ AF Li, G. Sokal, I. Quinn, J. F. Leverenz, J. B. Brodey, M. Schellenberg, G. D. Kaye, J. A. Raskind, M. A. Zhang, J. Peskind, E. R. Montine, T. J. TI CSF tau/A beta(42) ratio for increased risk of mild cognitive impairment - A follow-up study SO NEUROLOGY LA English DT Article ID CEREBROSPINAL-FLUID TAU; INCIPIENT ALZHEIMERS-DISEASE; PHOSPHORYLATED-TAU; CLINICAL-DIAGNOSIS; APOLIPOPROTEIN-E; MCI SUBJECTS; BIOMARKERS; PROTEIN; BETA-AMYLOID(1-42); DEMENTIA AB Background: Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and A beta(42) as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD. Methods: We determined the ratio of CSF tau/A beta(42) (T/A beta) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12). Results: We identified 16% of the control group with abnormally elevated CSF T/A beta; all were 53 years or older. Using age-matched controls with normal CSF T/A beta we showed that the high CSF T/A beta subgroup of controls had significantly increased frequency of the epsilon 4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture. Conclusions: These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Dept Behav Sci, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. Biosource Div Invitrogen, Camarillo, CA USA. RP Montine, TJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, 300 9th Ave, Seattle, WA 98104 USA. EM tmontine@u.washington.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG05136, AG08017] NR 35 TC 170 Z9 174 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 14 PY 2007 VL 69 IS 7 BP 631 EP 639 DI 10.1212/01.wnl.0000267428.62582.aa PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 199VP UT WOS:000248723600003 PM 17698783 ER PT J AU Silva, EF Medeiros, MA McBride, AJA Matsunaga, J Esteves, GS Ramos, JGR Santos, CS Croda, J Homma, A Dellagostin, OA Haake, DA Reis, MG Ko, AI AF Silva, Everton F. Medeiros, Marco A. McBride, Alan J. A. Matsunaga, Jim Esteves, Gabriela S. Ramos, Joao G. R. Santos, Cleiton S. Croda, Julio Homma, Akira Dellagostin, Odira A. Haake, David A. Reis, Mitermayer G. Ko, Albert I. TI The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis SO VACCINE LA English DT Article DE leptospirosis; subunit vaccine; leptospiral immunoglobulin-like protein; recombinant protein; immunity; antibodies; hamsters ID INTERROGANS SEROVAR POMONA; OUTER-MEMBRANE PROTEINS; URBAN EPIDEMIC; VACCINATION; CHALLENGE; VACCINES; MICE; IMMUNOPROTECTION; EXPRESSION; DISEASE AB Subunit vaccines are a potential intervention strategy against leptospirosis, which is a major public health problem in developing countries and a veterinary disease in livestock and companion animals worldwide. Leptospiral immunoglobulin-like (Lig) proteins are a family of surface-exposed determinants that have Ig-like repeat domains found in virulence factors such as intimin and invasin. We expressed fragments of the repeat domain regions of LigA and Lig]B from Leptospira interrogans serovar Copenhageni. Immunization of Golden Syrian hamsters with Lig fragments in Freund's adjuvant induced robust antibody responses against recombinant protein and native protein, as detected by ELISA and immunoblot, respectively. A single fragment, LigANI, which corresponds to the six carboxy-terminal Ig-like repeat domains of the LigA molecule, conferred immunoprotection against mortality (67-100%, P < 0.05) in hamsters which received a lethal inoculum of L. interrogans serovar Copenhageni. However, immunization with this fragment did not confer sterilizing immunity. These findings indicate that the carboxy-terminal portion of LigA is an immunoprotective domain and may serve as a vaccine candidate for human and veterinary leptospirosis. (c) 2007 Elsevier Ltd. All rights reserved. C1 Ctr Pesquisas Goncalo Moniz, Fundacao Oswaldo Cruz, BR-40296710 Salvador, BA, Brazil. Brazilian Minst Hlth, Oswaldo Curz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil. Univ Fed Pelotas, Ctr Biotechnol, Pelotas, Brazil. Vet Affairs Greater Los Angles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Giffen Sch Med, Dept Med, Los Angeles, CA USA. Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY USA. RP Ko, AI (reprint author), Ctr Pesquisas Goncalo Moniz, Fundacao Oswaldo Cruz, Rua Waldemar Falcao,121, BR-40296710 Salvador, BA, Brazil. EM aik2001@med.cornell.edu RI Dellagostin, Odir/C-2331-2009; Ko, Albert/P-2343-2015; McBride, Alan/D-4106-2012 OI Dellagostin, Odir/0000-0003-2803-4088; McBride, Alan/0000-0001-9682-540X FU FIC NIH HHS [D43 TW000919, D43 TW000919-10, TW00919]; NIAID NIH HHS [AI052473, AI034431, R01 AI034431, R01 AI034431-10A1, R01 AI052473, R01 AI052473-04, R21 AI034431, R29 AI034431] NR 48 TC 84 Z9 84 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 14 PY 2007 VL 25 IS 33 BP 6277 EP 6286 DI 10.1016/j.vaccine.2007.05.053 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 202MN UT WOS:000248905900016 PM 17629368 ER PT J AU Setty, AR Curhan, G Choi, HK AF Setty, Arathi R. Curhan, Gary Choi, Hyon K. TI Obesity, waist circumference, weight change, and the risk of psoriasis in women - Nurses' health study II SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LOW-GRADE INFLAMMATION; WHITE ADIPOSE-TISSUE; QUALITY-OF-LIFE; MACROPHAGE INFILTRATION; UNITED-STATES; GASTRIC BYPASS; POPULATION; PREVALENCE; SMOKING; REMISSION AB Background: Psoriasis is a common, chronic, inflammatory skin disorder. Higher adiposity may increase the risk of psoriasis, but, to our knowledge, no prospective data are available on this relationship. Methods: We prospectively examined the relationships between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight change, waist circumference, hip circumference, waist-hip ratio, and incident psoriasis in 78 626 women over a 14-year period (1991-2005) in the Nurses' Health Study II. The primary outcome was incident, self-reported, physician-diagnosed psoriasis. Results: During the 14 years of follow-up, there were 892 self-reported incident cases of psoriasis. There was a graded positive association between BMI measured at multiple time points and the risk of incident psoriasis. When we analyzed BMI updated every 2 years, compared with a BMI of 21.0 through 22.9, the multivariate relative risks of psoriasis were 1.40 (95% confidence interval [CI], 1.13-1.73) for a BMI of 25.0 through 29.9; 1.48 (95% CI, 1.15-1.91) for a BMI of 30.0 through 34.9; and 2.69 ( 95% CI, 2.12-3.40) for a BMI of 35.0 or greater (P for trend, <. 001). For BMI at the age of 18 years, the multivariate relative risk for the top BMI category (>= 30.0) was 1.73 (95% CI, 1.24-2.41) and that for a lower BMI category (< 21.0) was 0.76 (95% CI, 0.65-0.90) (P for trend, <. 001). Weight gain from the age of 18 years, higher waist circumference, hip circumference, and waist-hip ratio were all associated with a higher risk of incident psoriasis (all P values for trend, <. 001). Conclusion: This large prospective study indicates that increased adiposity and weight gain are strong risk factors for incident psoriasis in women. C1 Univ British Columbia, Vancouver Gen Hosp, Div Rheumatol, Arthritis Res Ctr Canada,Dept Med, Vancouver, BC V5Z 1L7, Canada. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Rheumat Allergy & Immunol, Boston, MA 02114 USA. RP Choi, HK (reprint author), Univ British Columbia, Dept Med, Div Rheumatol, Arthritis Res Ctr Canada, 895 W 10th Ave, Vancouver, BC V5Z 1L7, Canada. EM hchoi@arthritisresearch.ca FU NCI NIH HHS [CA50385]; NIAMS NIH HHS [5 T32 AR007258-29] NR 30 TC 223 Z9 227 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 13 PY 2007 VL 167 IS 15 BP 1670 EP 1675 DI 10.1001/archinte.167.15.1670 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 199KK UT WOS:000248694500014 PM 17698691 ER PT J AU Kusner, DJ Thompson, CR Melrose, NA Pitson, SM Obeid, LM Iyer, SS AF Kusner, David J. Thompson, Christopher R. Melrose, Natalie A. Pitson, Stuart M. Obeid, Lina M. Iyer, Shankar S. TI The localization and activity of sphingosine kinase 1 are coordinately regulated with actin cytoskeletal dynamics in macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID PHAGOSOME-LYSOSOME FUSION; MYCOBACTERIUM-TUBERCULOSIS PHAGOSOME; DEPENDENT SIGNAL-TRANSDUCTION; MEDIATED CA2+ MOBILIZATION; PROTEIN-COUPLED RECEPTORS; PHOSPHOLIPASE-D ACTIVITY; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM AB The physiologic and pathologic functions of sphingosine kinase (SK) require translocation to specific membrane compartments. Wetested the hypothesis that interactions with actin filaments regulate the localization of SK1 to membrane surfaces, including the plasma membrane and phagosome. Macrophage activation is accompanied by a marked increase in association of SK1 with actin filaments. Catalytically-inactive (CI)- and phosphorylation-defective (PD)-SK1 mutants exhibited reductions in plasma membrane translocation, colocalization with cortical actin filaments, membrane ruffling, and lamellipodia formation, compared with wild-type (WT)-SK1. However, translocation of CI- and PD-SK1 to phagosomes were equivalent to WT-SK1. SK1 exhibited constitutive- and stimulus-enhanced association with actin filaments and F-actin-enriched membrane fractions in both intact macrophages and a novel in vitro assay. In contrast, SK1 bound G-actin only under stimulated conditions. Actin inhibitors disrupted SK1 localization and modulated its activity. Conversely, reduction of SK1 levels or activity via RNA interference or specific chemical inhibition resulted in dysregulation of actin filaments. Thus, the localization and activity of SK1 are coordinately regulated with actin dynamics during macrophage activation. C1 Univ Iowa, Carver Coll Med, Inflammat Program, Div Infect Dis, Iowa City, IA 52245 USA. Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52245 USA. Univ Iowa, Carver Coll Med, Dept Physiol & Biophys, Iowa City, IA 52245 USA. Univ Iowa, Carver Coll Med, Grad Program Immunol, Iowa City, IA 52245 USA. Univ Iowa, Carver Coll Med, Grad Mol Biol, Iowa City, IA 52245 USA. Vet Affairs Med Ctr, Iowa City, IA 52245 USA. Univ Adelaide, Sch Mol & Biomed Sci, Inst Med & Vet Sci, Div Human Immunol,Hanson Inst, Adelaide, SA 5005, Australia. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Kusner, DJ (reprint author), 200 Hawkins Dr,SW54-8GH, Iowa City, IA 52245 USA. EM david-kusner@uiowa.edu OI obeid, lina/0000-0002-0734-0847 FU NIAID NIH HHS [R01 AI055916, P01 AI44642-08]; NIGMS NIH HHS [R01 GM62302, R01 GM062887]; PHS HHS [T32] NR 125 TC 19 Z9 22 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2007 VL 282 IS 32 BP 23147 EP 23162 DI 10.1074/jbc.M700193200 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 197ST UT WOS:000248577500017 PM 17519232 ER PT J AU Cohen, SE Kokkotou, E Biddinger, SB Kondo, T Gebhardt, R Kratzsch, J Mantzoros, CS Kahn, CR AF Cohen, Shmuel E. Kokkotou, Efi Biddinger, Sudha B. Kondo, Tatsuya Gebhardt, Rolf Kratzsch, Juergen Mantzoros, Christos S. Kahn, C. Ronald TI High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-VIVO; GENE-EXPRESSION; ADIPOSE-TISSUE; ENERGY-BALANCE; SERUM LEPTIN; RESISTANCE; OBESITY; MODULATION; IDENTIFICATION; GROWTH AB Liver-specific insulin receptor knock-out (LIRKO) mice display hyperinsulinemia, abnormal glucose metabolism, and progressive liver dysfunction. In addition, circulating leptin levels appear to be increased more than 10-fold. However, food intake, body weight, and adipose mass are not significantly altered in LIRKO mice compared with wild-type littermates. Using a ligand immunofunctional assay, we found that the apparent increase in circulating leptin in LIRKO mice is because of an 80-fold increased serum level of soluble leptin receptor. Gene expression analysis by microarray and real time PCR reveals the liver as the source of soluble leptin receptor in LIRKO mice, with an increase in expression of the short (Ob-Ra), long (Ob-Rb), and soluble (Ob-Re) forms of the leptin receptor. Direct control of leptin receptor expression by insulin could also be demonstrated in isolated hepatocytes from normal mice. Despite the markedly increased levels of leptin receptor in their circulation, LIRKO mice exhibit normal or even enhanced leptin sensitivity, as assessed by their physiological and molecular responses to exogenous leptin administration and their lower base-line hypothalamic levels of SOCS3 mRNA. Thus, insulin signaling in the liver plays an important role in control of leptin receptor expression and shedding. In the LIRKO mouse, this is lost, leading to markedly increased leptin receptors into the circulation. These high levels of circulating leptin receptor bind leptin and likely alter its clearance, but do not inhibit leptin action and may actually potentiate leptin action. In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Leipzig, Inst Biochem, D-04103 Leipzig, Germany. Univ Hosp, Inst Lab Med Clin Chem & Mol Diagnost, D-04103 Leipzig, Germany. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK33201, DK31036, P30 DK040561, P30 DK040561-12, P30-DK040561]; PHS HHS [R01-58785] NR 48 TC 36 Z9 40 U1 0 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 AUG 10 PY 2007 VL 282 IS 32 BP 23672 EP 23678 DI 10.1074/jbc.M704053200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 197ST UT WOS:000248577500070 PM 17556363 ER PT J AU Dormond, O Madsen, JC Briscoe, DM AF Dormond, Olivier Madsen, Joren C. Briscoe, David M. TI The effects of mTOR-Akt interactions on anti-apoptotic signaling in vascular endothelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; GROWTH-FACTOR; CYCLE PROGRESSION; MAMMALIAN TARGET; S6 KINASE; RAPAMYCIN; PATHWAY; PHOSPHORYLATION; ANGIOGENESIS; SURVIVAL AB Recent studies have determined that mTOR mediates the activation of the protein kinase Akt in several cell types, but little is known about the association between mTOR and Akt in vascular endothelial cells. Furthermore, the functional significance of mTOR/Akt signaling has not been characterized in the endothelium. In these studies we treated endothelial cells with the mTOR inhibitor rapamycin, and we found that it decreases Akt phosphorylation and activity, as determined by phosphorylation of its substrate glycogen synthase kinase-3. This effect of rapamycin on Akt phosphorylation could not be demonstrated in endothelial cells transfected with a rapamycin-resistant mTOR construct. Also, in the presence of rapamycin, vascular endothelial growth factor, tumor necrosis factor, and insulin failed to phosphorylate Akt, further indicating that mTOR regulates Akt activation in endothelial cells. The activation of Akt is well established to mediate pro-survival signals. In part this is mediated via the phosphorylation and inactivation of the proapoptotic Akt substrates Foxo1 and Foxo3a. We find that rapamycin totally blocks vascular endothelial growth factor and Aktinducible phosophorylation of these transcription factors in endothelial cells. Furthermore, inhibition of Akt activity by rapamycin increased the number of endothelial cells undergoing apoptosis after serum withdrawal as well as after stimulation by vascular endothelial growth factor or tumor necrosis factor. Taken together these observations demonstrate first, that mTOR regulates the phosphorylation and activation of Akt in endothelial cells and, second, that a major effect of mTOR inhibition in endothelial cells is to suppress Akt-inducible pro-survival signals. C1 Childrens Hosp, Div Nephrol, Dept Med, Transplant Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA 02114 USA. RP Briscoe, DM (reprint author), Childrens Hosp, Div Nephrol, Dept Med, Transplant Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM david.biscoe@childrens.harvard RI Dormond, Olivier/B-5347-2017 OI Dormond, Olivier/0000-0002-6418-1782 FU NIAID NIH HHS [R01 AI046756, R01 AI046756-06A1, R01AI046756] NR 51 TC 82 Z9 85 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2007 VL 282 IS 32 BP 23679 EP 23686 DI 10.1074/jbc.M700563200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 197ST UT WOS:000248577500071 PM 17553806 ER PT J AU Thomas, E Tabernero, J Fornier, M Conte, P Fumoleau, P Lluch, A Vahdat, LT Bunnell, CA Burris, HA Viens, P Baselga, J Rivera, E Guarneri, V Poulart, V Klimovsky, J Lebwohl, D Martin, M AF Thomas, Eva Tabernero, Josep Fornier, Monica Conte, Pierfranco Fumoleau, Pierre Lluch, Ana Vahdat, Linda T. Bunnell, Craig A. Burris, Howard A. Viens, Patrice Baselga, Jose Rivera, Edgardo Guarneri, Valentina Poulart, Valerie Klimovsky, Judith Lebwohl, David Martin, Miguel TI Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID ANTITUMOR EFFICACY; DOSE PACLITAXEL; CHEMOTHERAPY; INFUSION; CONFIDENCE; DOCETAXEL; 3-HOUR; LIMITS AB Purpose Ixabepilone (BMS- 247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy. Patients and Methods MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone ( 1- or 3-hour infusion of 50 mg/ m(2) or 3-hour infusion of 40 mg/ m(2) every 3 weeks). Results Of 49 patients treated with 40 mg/ m(2) ixabepilone during 3 hours, 35 ( 73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% Cl, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate. Conclusion Ixabepilone (40 mg/ m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane- resistant MBC. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Hosp, Dept Med Oncol, Barcelona, Spain. Hosp Clin Univ, Serv Oncol, Valencia, Spain. Hosp Clin San Carlos, Madrid, Spain. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Hosp, Dept Hematol & Oncol, Modena, Italy. Ctr Georges Francois Leclerc, Dijon, France. New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sarah Cannon Canc Ctr, Nashville, TN USA. Inst J Paoli I Calmettes, Ctr Reg Lutte Contre Canc, Serv Oncol Med 2, F-13009 Marseille, France. Bristol Myers Squibb Co, Princeton, NJ USA. RP Thomas, E (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM est5151@yahoo.com RI Fornier, Monica/F-5899-2010; Conte, PierFranco/F-7418-2014; OI Conte, PierFranco/0000-0002-5210-5344; MARTIN, MIGUEL/0000-0001-9237-3231 NR 28 TC 201 Z9 203 U1 0 U2 12 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 AUG 10 PY 2007 VL 25 IS 23 BP 3399 EP 3406 DI 10.1200/JCO.2006.08.9102 PG 8 WC Oncology SC Oncology GA 200DO UT WOS:000248744300005 PM 17606975 ER PT J AU Roche, H Yelle, L Cognetti, F Mauriac, L Bunnell, C Sparano, J Kerbrat, P Delord, JP Vahdat, L Peck, R Lebwohl, D Ezzeddine, R Cure, H AF Roche, Henri Yelle, Louise Cognetti, Francesco Mauriac, Louis Bunnell, Craig Sparano, Joseph Kerbrat, Pierre Delord, Jean-Pierre Vahdat, Linda Peck, Ronald Lebwohl, David Ezzeddine, Rana Cure, Herve TI Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, as first-line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT World Cancer Congress of the International-Union-Against-Cancer (UICC) CY JUL 08-12, 2006 CL Washington, DC SP Int Union Against Canc ID DOCETAXEL; PACLITAXEL; 5-FLUOROURACIL; MECHANISM; FAILURE; MBC AB Purpose There is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline. Patients and Methods Patients were age >= 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m(2) intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival. Results All 65 patients were assessable for response. Their median age was 52 years ( range, 33 to 80 years). ORR was 41.5% (95% Cl, 29.4% to 54.4%), median duration of response was 8.2 months (95% Cl, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% Cl, 15.6 to 27.0 months). Treatment- related adverse events were manageable and mostly grades 1/ 2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature. Conclusion Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline. C1 Inst Claudius Regaud, F-31052 Toulouse, France. Ctr Eugene Marquis, Rennes, France. Inst Bergonie, Bordeaux, France. Ctr Jean Perrin, Clermont Ferrand, France. Univ Montreal, Hop Notre Dame, Ctr Hosp, Montreal, PQ, Canada. IFO Ist Regina Elena, Comitato Etico Ist Ricovero Cura Carattere Sci, Rome, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Roche, H (reprint author), Inst Claudius Regaud, 20-24 Rue St Pierre, F-31052 Toulouse, France. EM roche.henri@claudiusregaud.fr RI Roche, Henri/O-9211-2014; DELORD, Jean-Pierre/I-8866-2014; OI Roche, Henri/0000-0001-7463-205X; Cognetti, Francesco/0000-0001-8498-151X NR 22 TC 159 Z9 163 U1 2 U2 8 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 AUG 10 PY 2007 VL 25 IS 23 BP 3415 EP 3420 DI 10.1200/JCO.2006.09.7535 PG 6 WC Oncology SC Oncology GA 200DO UT WOS:000248744300007 PM 17606972 ER PT J AU Saltz, LB Niedzwiecki, D Hollis, D Goldberg, RM Hantel, A Thomas, JP Fields, ALA Mayer, RJ AF Saltz, Leonard B. Niedzwiecki, Donna Hollis, Donna Goldberg, Richard M. Hantel, Alexander Thomas, James P. Fields, Anthony L. A. Mayer, Robert J. TI Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: Results of CALGB 89803 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID METASTATIC COLORECTAL-CANCER; RANDOMIZED-TRIAL; LEVAMISOLE; FAILURE; CPT-11 AB Purpose Randomized studies have shown that irinotecan (CPT- 11) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil (FU) plus leucovorin (LV) in first-line therapy of metastatic colorectal cancer. When this study was initiated, FU plus LV was standard adjuvant treatment for stage III colon cancer. We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer. Methods A total of 1,264 patients were randomly assigned to receive either standard weekly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV. The primary end points of the study were overall survival (OS) and disease- free survival (DFS). Results Treatment arms were well-balanced for patient characteristics and prognostic variables. There were no differences in either DFS or OS between the two treatment arms. Toxicity, including lethal toxicity, was significantly higher on the CPT-11 plus FU plus LV arm. Conclusion The addition of CPT-11 to weekly bolus FU plus LV did not result in improvement in DFS or OS in stage III disease, but did increase both lethal and nonlethal toxicity. This trial demonstrates that advances in the treatment of metastatic disease do not necessarily translate into advances in adjuvant treatment, and it reinforces the need for randomized controlled adjuvant studies. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Duke Univ, Dept Med, Durham, NC USA. Duke Univ, Dept Biostat, Durham, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Loyola Univ, Dept Med, Chicago, IL 60611 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Alberta, Dept Med, Edmonton, AB T6G 2M7, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Saltz, LB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM saltzl@mskcc.org RI Goldberg , Richard/M-1311-2013; OI Saltz, Leonard/0000-0001-8353-4670 FU NCI NIH HHS [2 U10 CA33601-25] NR 15 TC 216 Z9 218 U1 0 U2 3 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 AUG 10 PY 2007 VL 25 IS 23 BP 3456 EP 3461 DI 10.1200/JCO.2007.11.2144 PG 6 WC Oncology SC Oncology GA 200DO UT WOS:000248744300013 PM 17687149 ER PT J AU Dy, GK Krook, JE Green, EM Sargent, DJ Delaunoit, T Morton, RF Fuchs, CS Ramanathan, RK Williamson, SK Findlay, BP Pockaj, BA Sticca, RP Alberts, SR Pitot, HC Goldberg, RM AF Dy, Grace K. Krook, James E. Green, Erin M. Sargent, Daniel J. Delaunoit, Thierry Morton, Roscoe F. Fuchs, Charles S. Ramanathan, Ramesh K. Williamson, Stephen K. Findlay, Brian P. Pockaj, Barbara A. Sticca, Robert P. Alberts, Steven R. Pitot, Henry C. Goldberg, Richard M. TI Impact of complete response to chemotherapy on overall survival in advanced colorectal cancer: Results from intergroup N9741 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LIVER METASTASES; RANDOMIZED-TRIAL; PREOPERATIVE CHEMOTHERAPY; FLUOROURACIL FAILURE; CONTINUOUS-INFUSION; 1ST-LINE TREATMENT; PLUS IRINOTECAN; PHASE-III; OXALIPLATIN; LEUCOVORIN AB Purpose To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach. Patients and Methods Data were collected retrospectively from CRC patients enrolled onto the phase III trial N9741, a National Cancer Institute-funded and Gastrointestinal Cancer Intergroup-sponsored study coordinated by the North Central Cancer Treatment Group. Patients were randomly assigned to combinations of oxaliplatin, fluorouracil (FU)/ leucovorin (LV) and irinotecan. The three treatment arms consist of IFL (irinotecan + FU/ LV), FOLFOX4 (oxaliplatin + FU/ LV), and IROX (irinotecan + oxaliplatin). Median follow-up was 42.6 months. Results Sixty-two (4%) of 1,508 patients had a CR to chemotherapy alone, and an additional 32 (2%) had a CR after multimodality treatment. Factors associated with achieving CR with systemic chemotherapy alone included FOLFOX4 treatment, patients with assessable disease, or a single site of metastasis. Continuing protocol treatment beyond two cycles after documentation of CR was not associated with improved survival. The rate of curative intent resection was significantly higher for patients treated with oxaliplatin- containing regimens (P =.02). Median survival was similar between patients with CR after chemotherapy alone (44.3 months) or after multimodality approach (47.4 months; P =.81). Conclusion FOLFOX4 was more likely to produce a CR than were IFL or IROX. Oxaliplatin regimens were more likely to result in successful surgical resections. Patients who have CR to systemic chemotherapy alone can achieve impressive survival outcomes similar to those seen among patients who attained a CR status after multimodality treatment. C1 Mayo Clin, Rochester, MN 55905 USA. Mayo Fdn, Rochester, MN USA. Duluth CCOOP, Duluth, MN USA. Jolimont Hosp, La Louviere, Belgium. Iowa Oncol Res Assoc CCOP, Moines, IA USA. Dana Farber Canc Ctr Inst, Boston, MA USA. Univ Pittsburgh, Ctr Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NCI, St Catharines, ON, Canada. Univ N Dakota, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. Univ N Carolina, Chapel Hill, NC USA. RP Dy, GK (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM dy.grace@mayo.edu RI Goldberg , Richard/M-1311-2013; OI Sargent, Daniel/0000-0002-2684-4741 FU NCI NIH HHS [CA-21115, CA-25224, CA-32102, CA-35101, CA-35195, CA-37404, CA-38926] NR 25 TC 39 Z9 41 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 AUG 10 PY 2007 VL 25 IS 23 BP 3469 EP 3474 DI 10.1200/JCO.2007.10.7128 PG 6 WC Oncology SC Oncology GA 200DO UT WOS:000248744300015 PM 17687151 ER PT J AU Mansy, SS Zhang, JL Kummerle, R Nilsson, M Chou, JJ Szostak, JW Chaput, JC AF Mansy, Sheref S. Zhang, Jinglei Kuemmerle, Rainer Nilsson, Mikael Chou, James J. Szostak, Jack W. Chaput, John C. TI Structure and evolutionary analysis of a non-biological ATP-binding protein SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE mRNA display; solution NMR; in vitro evolution ID COUPLING-CONSTANTS; GLOBULAR-PROTEINS; DISTANCE GEOMETRY; NMR-SPECTROSCOPY; CHEMICAL-SHIFT; RESONANCE; RELAXATION; ASSIGNMENT; PREDICTION; DIPOLAR AB We present a structural and functional analysis of the evolutionary optimization of a non-biological protein derived from a library of random amino acid sequences. A series of previously described in vitro selection experiments transformed a low-affinity ancestral sequence into a stably folded, high affinity ATP binding protein structure. While the evolutionarily optimized protein differs from its ancestral sequence through the accumulation of 12 amino acid mutations, the means by which those mutations enhance the stability and functionality of the protein were not well understood. We used a combination of mutagenesis, biochemistry, and NMR spectroscopy to investigate the structural and functional significance of each mutation. We solved the three-dimensional structure of the folding optimized protein by solution NMR, which revealed a fourth strand of the beta-sheet of the alpha/beta-fold that was not observed in an earlier crystallographic analysis of a less stable version of the protein. The structural rigidity of the newly identified -strand was confirmed by T-1, T-2, and heteronuclear nuclear Overhauser enhancement (NOE) measurements. Biochemical experiments were used to examine point mutations that revert the optimized protein back to the ancestral residue at each of the 12 sites. A combination of structural and functional data was then used to interpret the significance of each amino acid mutation. The enhanced ATP affinity was largely due to the emergence of a patch of positive charge density on the protein surface, while the increased solubility resulted from several mutations that increased the hydrophilicity of the protein surface, thereby decreasing protein aggregation. One mutation may stabilize the hydrophobic face of the beta-sheet. (C) 2007 Elsevier Ltd. All rights reserved. C1 Arizona State Univ, Ctr BioOpt Nanotechnol, Biodesign Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Bruker BioSpin AG, Fallanden, Switzerland. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Chaput, JC (reprint author), Arizona State Univ, Ctr BioOpt Nanotechnol, Biodesign Inst, Tempe, AZ 85287 USA. EM john.chaput@asu.edu RI Mansy, Sheref/E-6266-2010; Nilsson, Mikael/E-9867-2013; Chou, James/N-9840-2013; OI Mansy, Sheref/0000-0003-2382-198X FU NIGMS NIH HHS [F32 GM07450601] NR 41 TC 10 Z9 10 U1 1 U2 14 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 10 PY 2007 VL 371 IS 2 BP 501 EP 513 DI 10.1016/j.jmb.2007.05.062 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196VA UT WOS:000248509100020 PM 17583732 ER PT J AU Marvizon, JCG Perez, OA Song, B Chen, W Bunnett, NW Grady, EF Todd, AJ AF Marvizon, J. C. G. Perez, O. A. Song, B. Chen, W. Bunnett, N. W. Grady, E. F. Todd, A. J. TI Calcitonin receptor-like and receptor activity modifying protein 1 in the rat dorsal horn localization in glutamatergic presynaptic terminal containing opioids and adrenergic alpha(2c) receptor SO NEUROSCIENCE LA English DT Article DE adrenergic receptor; calcitonin gene-related peptide; CGRP; colocalization; dynorphin; enkephalin ID GENE-RELATED-PEPTIDE; LAMINAE-I-III; SPINAL-CORD; SUBSTANCE-P; CALCIUM-CHANNELS; ALPHA(2C)-ADRENERGIC RECEPTOR; SUPERFICIAL LAMINAE; SYNAPTIC GLOMERULI; PRIMARY AFFERENTS; HUMAN CEREBELLUM AB Calcitonin gene-related peptide (CGRP) is abundant in the central terminals of primary afferents. However, the function of CGRP receptors in the spinal cord remains unclear. CGRP receptors are heterodimers of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1). We studied the localization of CRLR and RAMP1 in the rat dorsal horn using well-characterized antibodies against them, which labeled numerous puncta in laminae I-II. In addition, RAMP1 was found in cell bodies, forming patches at the cell surface. The CRLR- and RAMP1-immunoreactive puncta were further characterized using double and triple labeling. Colocalization was quantified in confocal stacks using Imaris software. CRLR did not colocalize with primary afferent markers, indicating that these puncta were not primary afferent terminals. CRLR- and RAMP1-immunoreactive puncta contained synaptophysin and vesicular glutamate transporter-2 (VGLUT2), showing that they were glutamatergic presynaptic terminals. Electron microscopic immunohistochemistry confirmed that CRLR immunoreactivity was present in axonal boutons that were not in synaptic glomeruli. Using tyramide signal amplification for double labeling with the CRLR and RAMP1 antibodies, we found some clear instances of colocalization of CRLR with RAMP1 in puncta, but their overall colocalization was low. In particular, CRLR was absent from RAMP1-containing cells. Many of the puncta stained for CRLR and RAMP1 were labeled by antiopioid and anti-enkephalin antibodies. CRLR and, to a lesser extent, RAMP1 also colocalized with adrenergic alpha(2c) receptors. Triple label studies demonstrated three-way colocalization of CRLR-VGLUT2-synaptophysin, CRLR-VGLUT2-opioids, and CRLR-opioids-alpha(2c) receptors. In conclusion, CRLR is located in glutamatergic presynaptic terminals in the dorsal horn that contain alpha(2c) adrenergic receptors and opioids. Some of these terminals contain RAMP1, which may form CGRP receptors with CRLR, but in others CRLR may form other receptors, possibly by dimerizing with RAMP2 or RAMP3. These findings suggest that CGRP or adrenomedullin receptors modulate opioid release in the dorsal horn. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth & CURE, Digest Dis Res Ctr, Div Digest Dis,Dept Med,David Geffen Sch Med, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif San Francisco, Dept Physiol, Dept Surg, San Francisco, CA 94143 USA. Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. RP Marvizon, JCG (reprint author), Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth & CURE, Digest Dis Res Ctr, Div Digest Dis,Dept Med,David Geffen Sch Med, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu RI Todd, Andrew/A-6855-2011; Chen, Wenling/A-4490-2012 FU NIDA NIH HHS [2-R01-DA012609, R01 DA012609, R01 DA012609-06A1, R01 DA012609-07]; Wellcome Trust [, 076976] NR 54 TC 40 Z9 40 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG 10 PY 2007 VL 148 IS 1 BP 250 EP 265 DI 10.1016/j.neuroscience.2007.05.036 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 206BC UT WOS:000249157900023 PM 17614212 ER PT J AU Guzman-Marin, R Bashir, T Suntsova, N Szymusiak, R McGinty, D AF Guzman-Marin, R. Bashir, T. Suntsova, N. Szymusiak, R. McGinty, D. TI Hippocampal neurogenesis is reduced by sleep fragmentation in the adult rat SO NEUROSCIENCE LA English DT Article DE sleep fragmentation; hippocampus; dentate gyrus; neurogenesis; BrdU ID DENTATE GYRUS; CELL-PROLIFERATION; SUPPRESSES NEUROGENESIS; DAYTIME FUNCTION; RECOVERY SLEEP; DEPRIVATION; BRAIN; PERFORMANCE; DISRUPTION; APNEA AB The adult hippocampal dentate gyrus (DG) is a site of continuing neurogenesis. This process is influenced by a variety of physiological and experiential stimuli including total sleep deprivation (TSD). In humans, sleep fragmentation (SF) is a more common sleep condition than TSD. SF is associated with several prevalent diseases. We assessed a hypothesis that SF would suppress adult neurogenesis in the DG of the adult rat. An intermittent treadmill system was used; the treadmill was on for 3 s and off for 30 s (SF). For sleep fragmentation control (SFC), the treadmill was on for 15 min and off for 150 min. SF was conducted for three durations: 1, 4 and 7 days. To label proliferating cells, the thymidine analog, 5-bromo-2-deoxyuridine (BrdU), was injected 2 h prior to the end of each experiment. Expression of the intrinsic proliferative marker, Ki67, was also studied. SF rats exhibited an increased number of non-rapid eye movement (NREM) sleep bouts with no change in the percent of time spent in this stage. The numbers of both BrdU-positive cells and Ki67-positive cells were reduced by similar to 70% (P<0.05) in the SF groups after 4 and 7 days of experimental conditions whereas no differences were observed after 1 day. In a second experiment, we found that the percentage of new cells expressing a neuronal phenotype 3 weeks after BrdU administration was lower in the SF in comparison with the SFC group for all three durations of SF. We also examined the effects of SF on proliferation in adrenalectomized (ADX) animals, with basal corticosterone replacement. ADX SF animals exhibited a 55% reduction in the number of BrdU-positive cells when compared with ADX SFC. Thus, elevated glucocorticoids do not account for most of the reduction in cell proliferation induced by the SF procedure, although a small contribution of stress is not excluded. The results show that sustained SF induced marked reduction in hippocampal neurogenesis. Published by Elsevier Ltd on behalf of IBRO. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344006, Russia. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [P50 HL060296-080010, P50 HL060296]; NIMH NIH HHS [R01 MH075076, R01 MH075076-01A2] NR 53 TC 65 Z9 68 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG 10 PY 2007 VL 148 IS 1 BP 325 EP 333 DI 10.1016/j.neuroscience.2007.05.030 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 206BC UT WOS:000249157900029 PM 17630219 ER PT J AU Cole, AJ Henson, JW Roehrl, MHA Frosch, MP Harris, NL Cort, AM AF Cole, Andrew J. Henson, John W. Roehrl, Michael H. A. Frosch, Matthew P. Harris, Nancy Lee Cort, Alice M. TI A 20-year-old pregnant woman with altered mental status - Subacute sclerosing panencephalitis secondary to measles virus infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTRAVENTRICULAR ALPHA-INTERFERON; CENTRAL NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; ONSET; DISEASE; CSF; ISOPRINOSINE; RUBELLA; PROFILE; COMMON C1 Massachusetts Gen Hosp, Serv Neurol, 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 Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. NR 29 TC 5 Z9 5 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 AUG 9 PY 2007 VL 357 IS 6 BP 589 EP 600 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 197VP UT WOS:000248584900012 PM 17687135 ER PT J AU DeYoung, MP Ellisen, LW AF DeYoung, M. P. Ellisen, L. W. TI p63 and p73 in human cancer: defining the network SO ONCOGENE LA English DT Review DE p53; p63; p73; apoptosis; tumorigenesis; squamous cell carcinoma (SCC) ID SQUAMOUS-CELL CARCINOMA; YES-ASSOCIATED PROTEIN; P53 TARGET GENES; FAMILY-MEMBERS P63; KINASE C-ABL; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVITY; TUMOR-SUPPRESSOR; BREAST-CANCER; LUNG-CANCER AB The p53-related genes p63 and p73 exhibit signicant structural homology to p53; however, they do not function as classical tumor suppressors and are rarely mutated in human cancers. Both p63 and p73 exhibit tissue-specific roles in normal development and a complex contribution to tumorigenesis that is due to their expression as multiple protein isoforms. The predominant p63/p73 isoforms expressed both in normal development and in many tumors lack the conserved transactivation ( TA) domain; these isoforms instead exhibit a truncated N-terminus (DN) and function at least in part as transcriptional repressors. p63 and p73 isoforms are regulated through both transcriptional and post-translational mechanisms, and they in turn regulate diverse cellular functions including proliferation, survival and differentiation. The net effect of p63/p73 expression in a given context depends on the ratio of TA/DN isoforms expressed, on physical interaction between p63 and p73 isoforms, and on functional interactions with p53 at the promoters of specific downstream target genes. These multifaceted interactions occur in diverse ways in tumor-specific contexts, demonstrating a functional 'p53 family network' in human tumorigenesis. Understanding the regulation and mechanistic contributions of p63 and p73 in human cancers may ultimately provide new therapeutic opportunities for a variety of these diseases. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ-904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NIDCR NIH HHS [DE-15945, R01 DE015945] NR 159 TC 149 Z9 160 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 9 PY 2007 VL 26 IS 36 BP 5169 EP 5183 DI 10.1038/sj.onc.1210337 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 199CQ UT WOS:000248674200001 PM 17334395 ER PT J AU Silverman, JB Restituito, S Lu, W Lee-Edwards, L Khatri, L Ziff, EB AF Silverman, Joshua B. Restituito, Sophie Lu, Wei Lee-Edwards, Laveria Khatri, Latika Ziff, Edward B. TI Synaptic anchorage of AMPA receptors by cadherins through neural plakophilin-related arm protein-AMPA receptor-binding protein complexes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GluR2; AMPA receptor; ABP; GRIP; cadherin; NPRAP ID DOMAIN-CONTAINING PROTEINS; CELL-ADHESION MOLECULES; DELTA-CATENIN; DIFFERENTIAL PALMITOYLATION; POSTSYNAPTIC DENSITY; ADHERENS JUNCTION; ARMADILLO FAMILY; REPEAT PROTEIN; NMDA RECEPTOR; PDZ DOMAINS AB Cadherins function in the adhesion of presynaptic and postsynaptic membranes at excitatory synapses. Here we show that the cadherin-associated protein neural plakophilin-related arm protein (NPRAP; also called delta-catenin) binds via a postsynaptic density-95 (PSD-95)/ discs large/zona occludens-1 (PDZ) interaction to AMPA receptor (AMPAR)-binding protein (ABP) and the related glutamate receptor (GluR)-interacting protein (GRIP), two multi-PDZ proteins that bind the GluR2 and GluR3 AMPAR subunits. The resulting cadherin NPRAP -ABP/GRIP complexes serve as anchorages for AMPARs. Exogenous NPRAP that was bound to cadherins at adherens junctions of Madin-Darby canine kidney cells recruited ABP from the cytosol to form cadherin-NPRAP-ABP complexes, dependent on NPRAP interaction with the ABP PDZ domain 2. The cadherin-NPRAP-ABP complexes also bound GluR2. In cultured hippocampal neurons, dominant-negative mutants of NPRAP designed to disrupt tethering of ABP to NPRAP-cadherin complexes reduced surface levels of endogenous GluR2, indicating that interaction with cadherin - NPRAP - ABP complexes stabilized GluR2 at the neuronal plasma membrane. Cadherins, NPRAP, GRIP, and GluR2 copurified in the fractionation of synaptosomes and the postsynaptic density, two fractions enriched in synaptic proteins. Furthermore, synaptosomes contain NPRAP-GRIP complexes, and NPRAP localizes with the postsynaptic marker PSD- 95 and with AMPARs and GRIP at spines of hippocampal neurons. Thus, tethering is likely to take place at synaptic or perisynaptic sites. NPRAP also binds PSD- 95, which is a scaffold for NMDA receptors, for AMPARs in complexes with auxiliary subunits, the TARPs (transmembrane AMPA receptor regulator proteins), and for adhesion molecules. Thus, the interaction of scaffolding proteins with cadherin-NPRAP complexes may anchor diverse signaling and adhesion molecules at cadherins. C1 Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NYU, Sch Med, Program Neurosci & Physiol, New York, NY 10016 USA. RP Ziff, EB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM edward.ziff@med.nyu.edu RI Lu, Wei/E-8110-2011 FU NCRR NIH HHS [S10 RR017970]; NIA NIH HHS [AG13620]; NIGMS NIH HHS [T32 GM07308] NR 61 TC 64 Z9 66 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 8 PY 2007 VL 27 IS 32 BP 8505 EP 8516 DI 10.1523/JNEUROSCI.1395-07.2007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 199PT UT WOS:000248708400004 PM 17687028 ER PT J AU Griffin, RS Costigan, M Brenner, GJ Ma, CHE Scholz, J Moss, A Allchorne, AJ Stahl, GL Woolf, CJ AF Griffin, Robert S. Costigan, Michael Brenner, Gary J. Ma, Chi Him Eddie Scholz, Joachim Moss, Andrew Allchorne, Andrew J. Stahl, Gregory L. Woolf, Clifford J. TI Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE pain; immunity; complement cascade; spinal cord; dorsal horn; microarray; microglia; neuropathic pain ID PERIPHERAL-NERVE INJURY; DORSAL-ROOT GANGLION; NEUROPATHIC PAIN; GENE-EXPRESSION; CYTOKINE EXPRESSION; C5A RECEPTOR; GLIAL ACTIVATION; MESSENGER-RNA; RAT MODEL; MECHANICAL ALLODYNIA AB Microarray expression profiles reveal substantial changes in gene expression in the ipsilateral dorsal horn of the spinal cord in response to three peripheral nerve injury models of neuropathic pain. However, only 54 of the 612 regulated genes are commonly expressed across all the neuropathic pain models. Many of the commonly regulated transcripts are immune related and include the complement components C1q, C3, and C4, which we find are expressed only by microglia. C1q and C4 are, moreover, the most strongly regulated of all 612 regulated genes. In addition, we find that the terminal complement component C5 and the C5a receptor (C5aR) are upregulated in spinal microglia after peripheral nerve injury. Mice null for C5 had reduced neuropathic pain sensitivity, excluding C3a as a pain effector. C6-deficient rats, which cannot form the membrane attack complex, have a normal neuropathic pain phenotype. However, C5a applied intrathecally produces a dose-dependent, slow-onset cold pain in naive animals. Furthermore, a C5aR peptide antagonist reduces cold allodynia in neuropathic pain models. We conclude that induction of the complement cascade in spinal cord microglia after peripheral nerve injury contributes to neuropathic pain through the release and action of the C5a anaphylatoxin peptide. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Harvard Med Sch, Ctr Expt Therapeut & reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM cwoolf@partners.org OI MA, Chi Him Eddie/0000-0003-2054-0445 FU NINDS NIH HHS [K08 NS044139, NS038253, NS044139, NS052623, R01 NS038253]; PHS HHS [RDE017821A] NR 75 TC 117 Z9 122 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 8 PY 2007 VL 27 IS 32 BP 8699 EP 8708 DI 10.1523/JNEUROSCI.2018-07.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 199PT UT WOS:000248708400023 PM 17687047 ER PT J AU Nasir, K Budoff, MJ Wong, ND Scheuner, M Herrington, D Arnett, DK Szklo, M Greenland, P Blumenthal, RS AF Nasir, Khurram Budoff, Matthew J. Wong, Nathan D. Scheuner, Maren Herrington, David Arnett, Donna K. Szklo, Moyses Greenland, Philip Blumenthal, Roger S. TI Family history of premature coronary heart disease and coronary artery calcification - Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Article DE epidemiology; atherosclerosis; risk factors ID MIDDLE-AGED ADULTS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; CALCIUM SCORE; CHOLESTEROL; PREVENTION; WOMEN; ASSOCIATION; AMERICAN; ACCURACY AB Background - A family history of premature coronary heart disease (CHD) is a known risk factor for CHD events. The purpose of this study was to assess the strength of the association between a family history of premature CHD and coronary artery calcification (CAC) in a multiethnic cohort of asymptomatic individuals. We also sought to determine whether individuals with a reported family history of premature CHD have an increased atherosclerotic burden among those classified as being at low to intermediate risk on the basis of the conventional Framingham risk score. Methods and Results - The association of family history of premature CHD with CAC was assessed in 5347 asymptomatic individuals (47% men; mean age 62 +/- 10 years) in the Multi- Ethnic Study of Atherosclerosis (MESA). The demographics ( age, gender, and race) - adjusted OR for CAC > 0 with versus without a family history of premature CHD was 1.94 (95% CI, 1.64 to 2.29). On adjustment for CHD risk factors, the association was slightly attenuated to an OR of 1.84 (95% CI, 1.55 to 2.19). Family history of premature CHD was significantly associated with CAC in all ethnic groups. The age-, gender-, and race-adjusted prevalence of CAC > 0 was significantly higher with presence of any family history of premature CHD than for those with no family history of premature CHD among individuals classified as low risk (35% versus 23%, P < 0.0001) and among those at intermediate risk (70% versus 60%, P = 0.01). Similarly, the prevalence of age- gender-race-based CAC >= 75th percentile in low-risk (24% versus 14%, P = 0.0003) and intermediate-risk (34% versus 20%, P < 0.001) individuals was also higher among those with a family history of premature CHD. Compared with those without a family history of premature CHD, the association with the presence of CAC was strongest in participants reporting such history in both a parent and a sibling (odds ratio, 2.74; 95% CI, 1.64 to 4.59), followed by those reporting a family history in a sibling only (odds ratio, 2.06; 95% CI, 1.64 to 2.58) and those reporting a family history of premature CHD only in a parent ( odds ratio, 1.52; 95% CI, 1.19 to 1.93). Conclusions - An association between family history of premature CHD and the presence of any CAC, as well as advanced CAC, was observed in the present population-based multiethnic study. The relationship was independent of other risk factors and Framingham risk score, which supports the utility of including information on family history of premature CHD in current methods of global risk assessment and practice guidelines. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. Harbor UCLA Med Ctr, Los Angles Biomed Res Inst, Torrance, CA 90509 USA. Univ Calif Irvine, Dept Med, Heart Dis Prevent Program, Irvine, CA USA. RAND Corp, Santa Monica, CA USA. Wake Forest Univ, Sch Med, Dept Internal Med Cardiol, Winston Salem, NC 27109 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Blumenthal, RS (reprint author), Johns Hopkins Univ Hosp, Ciccarone Prevent Cardiol Ctr, Div Cardiol, Blalock 524 C,600 N Wolfe St, Baltimore, MD 21287 USA. EM rblument@jhmi.edu FU NHLBI NIH HHS [1T32 HL076136-02] NR 32 TC 83 Z9 86 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 7 PY 2007 VL 116 IS 6 BP 619 EP 626 DI 10.1161/CIRCULATIONAHA.107.688739 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 197QZ UT WOS:000248572300011 PM 17646582 ER PT J AU Masland, RH Martin, PR AF Masland, Richard H. Martin, Paul R. TI The unsolved mystery of vision SO CURRENT BIOLOGY LA English DT Article ID LATERAL GENICULATE-NUCLEUS; RETINAL GANGLION-CELLS; PRIMARY VISUAL-CORTEX; LOCAL EDGE DETECTORS; RECEPTIVE-FIELDS; MAMMALIAN RETINA; PRIMATE RETINA; RABBIT RETINA; MOUSE RETINA; CAT C1 Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3052, Australia. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM richard_masland@hms.harvard.edu RI Martin, Paul/A-4346-2009 OI Martin, Paul/0000-0002-5166-9658 NR 55 TC 21 Z9 21 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 7 PY 2007 VL 17 IS 15 BP R577 EP R582 DI 10.1016/j.cub.2007.05.040 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199AW UT WOS:000248669600007 PM 17686423 ER PT J AU Goy, ER Carter, JH Ganzini, L AF Goy, Elizabeth R. Carter, Julie H. Ganzini, Linda TI Parkinson disease at the end of life: Caregiver perspectives SO NEUROLOGY LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Columbia Ctr Study Chron, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Parkinsons Ctr Oregon, Portland, OR 97201 USA. RP Goy, ER (reprint author), Portland VA Med Ctr, P3 MHDC,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM goye@ohsu.edu NR 6 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 7 PY 2007 VL 69 IS 6 BP 611 EP 612 DI 10.1212/01.wnl.0000266665.82754.61 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 197RE UT WOS:000248573000017 PM 17679683 ER PT J AU Koulmanda, M Budo, E Bonner-Weir, S Qipo, A Putheti, P Degauque, N Shi, H Fan, ZG Flier, JS Auchincloss, H Zheng, XX Strom, TB AF Koulmanda, Maria Budo, Ejona Bonner-Weir, Susan Qipo, Andi Putheti, Prabhakar Degauque, Nicolas Shi, Hang Fan, Zhigang Flier, Jeffrey S. Auchincloss, Hugh, Jr. Zheng, Xin Xiao Strom, Terry B. TI Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; diabetes; NOD mice; tolerance; transplantation ID REGULATORY T-CELLS; ALLOGRAFT TOLERANCE; INSULIN-RESISTANCE; PANCREATIC-ISLETS; IL-15 RECEPTOR; AUTOIMMUNE; MICE; DEATH; PROGRESSION; EXENDIN-4 AB in nonobese diabetic (NOD) mice with overt new-onset type 1 diabetes mellitus (T1DM), short-term treatment with a "triple-therapy" regimen [rapamycin plus agonist IL-2-related and antagonist-type, mutant IL-15-related Ig fusion proteins (IL-2.Ig and mutIL-15.lg)] halts autoimmune destruction of insulin-producing beta cells and restores both euglycemia and immune tolerance to beta cells. Increases in the mass of insulin-producing beta cells or circulating insulin levels were not linked to the restoration of euglycemia. instead, the restoration of euglycemia was linked to relief from an inflammatory state that impaired the host's response to insulin. Both restoration of immune tolerance to beta cells and relief from the adverse metabolic effects of an inflammatory state in insulin-sensitive tissues appear essential for permanent restoration of normoglycemia in this T1DM model. Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in T1DIM. C1 Beth Israel Deaconess Med Ctr, Transplant Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Islet Transplant Res Lab, Boston, MA 02114 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Endocrinol, Boston, MA 02215 USA. RP Koulmanda, M (reprint author), Beth Israel Deaconess Med Ctr, Transplant Res Ctr, 77 Ave Louis Pasteur,HIM 1027-8, Boston, MA 02115 USA. EM mkoulman@bidmc.harvard.edu OI Degauque, Nicolas/0000-0003-2990-3513 FU NIAID NIH HHS [P01-AI041521, R01 AI54976, P01 AI041521, R01 AI054976]; NIDDK NIH HHS [R01 DK066056, R37 DK028082, DK 44523, DK 66056, R37 DK 28082, R01 DK067632, R01 DK044523] NR 32 TC 50 Z9 53 U1 0 U2 4 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 AUG 7 PY 2007 VL 104 IS 32 BP 13074 EP 13079 DI 10.1073/pnas.0705863104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300023 PM 17670937 ER PT J AU Juszczynski, P Ouyang, J Monti, S Rodig, SJ Takeyama, K Abramson, J Chen, W Kutok, JL Rabinovich, GA Shipp, MA AF Juszczynski, Przemyslaw Ouyang, Jing Monti, Stefano Rodig, Scott J. Takeyama, Kunihiko Abramson, Jeremy Chen, Wen Kutok, Jeffery L. Rabinovich, Gabriel A. Shipp, Margaret A. TI The AP1-dependent secretion of galectin-1 by Reed - Sternberg cells fosters immune privilege in classical Hodgkin lymphoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunomodulation; microenvironment; Th2; T-reg; c-Jun ID REGULATORY T-CELLS; FALSE DISCOVERY RATE; INFLAMMATORY RESPONSE; GENE-EXPRESSION; APOPTOSIS; PROMOTER; DISEASE; TARGET; DEATH; SUPPRESSION AB Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (T-reg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-l (Gall), through an AP1-dependent enhancer. In cocultures of activated T cells and Hodgkin cell lines, RNAi-mediated blockade of RS cell Gall increased T cell viability and restored the Thl/Th2 balance. In contrast, Gall treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4(+)CD25(high) FOXP3(+) T-reg cells. These data directly implicate RS cell Gall in the development and maintenance of an immunosuppressive Th2/T-reg-skewed microenvironment in cHL and provide the molecular basis for selective Gall expression in RS cells. Thus, Gall represents a potential therapeutic target for restoring immune surveillance in cHL. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Consejo Nacl Invest Cient & Tecn, Inst Expt Biol & Med, Buenos Aires, DF, Argentina. Univ Buenos Aires, Fac Exact & Nat Sci, Dept Biol Chem, Buenos Aires, DF, Argentina. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu OI Monti, Stefano/0000-0002-9376-0660 NR 45 TC 161 Z9 167 U1 1 U2 5 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 AUG 7 PY 2007 VL 104 IS 32 BP 13134 EP 13139 DI 10.1073/pnas.0706017104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198TL UT WOS:000248650300033 PM 17670934 ER PT J AU Tyeklar, Z Dunham, SU Midelfort, K Scott, DM Sajiki, H Ong, K Lauffer, RB Caravan, P McMurry, TJ AF Tyeklar, Zoltan Dunham, Stephen U. Midelfort, Katarina Scott, Daniel M. Sajiki, Hirano Ong, Karen Lauffer, Randall B. Caravan, Peter McMurry, Thomas J. TI Structural, kinetic, and thermodynamic characterization of the interconverting isomers of MS-325, a gadolinium(III)-based magnetic resonance angiography contrast agent SO INORGANIC CHEMISTRY LA English DT Article ID AORTOILIAC OCCLUSIVE DISEASE; PERIPHERAL VASCULAR-DISEASE; HUMAN SERUM-ALBUMIN; MR-ANGIOGRAPHY; CRYSTAL-STRUCTURES; DIETHYLENETRIAMINEPENTAACETIC ACID; PHYSICOCHEMICAL CHARACTERIZATION; AMINOPOLYCARBOXYLIC ACIDS; LANTHANIDE COMPLEXES; INITIAL-EXPERIENCE AB The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 comprises a GdDTPA core with an appended phosphodiester moiety linked to a diphenylcyclohexyl group to facilitate noncovalent binding to serum albumin and extension of the plasma half-life in vivo. The chiral DTPA ligand (R) was derived from l-serine, and upon complexation with gadolinium, forms two interconvertible diastereomers, denoted herein as isomers A and B. X-ray crystallography of the tris(ethylenediamine)cobalt(III) salt derivative of isomer A revealed a structure in the polar acentric space group P3(2). The structure consisted of three independent molecules of the gadolinium complex in the asymmetric unit along with three Delta-[Co(en)(3)](3+) cations, and it represents an unusual example of spontaneous Pasteur resolution of the cobalt cation. The geometry of the coordination core was best described as a distorted trigonal prism, and the final R factor was 5.6%. The configuration of the chiral central nitrogen of the DTPA core was S. The Gd-water (2.47-2.48 angstrom), the Gd-acetate oxygens (2.34-2.42 angstrom), and the Gd-N bond distances (central N, 2.59-2.63 angstrom; terminal N, 2.74-2.80 angstrom) were similar to other reported GdDTPA structures. The structurally characterized single crystal was one of two interconvertable diastereomers (isomers A and B) that equilibrated to a ratio of 1.81 to 1 at pH 7.4 and were separable at elevated pH by ion-exchange chromatography. The rate of isomerization was highly pH dependent: k(1) = (1.45 +/- 0.08) x 10(2)[H+] + (4.16 +/- 0.30) x 10(5)[H+](2); k(-1) = (2.57 +/- 0.17) x 10(2)[H+] + (7.54 +/- 0.60) x 10(5)[H+](2). C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EPIX Pharmaceut Inc, Cambridge, MA 02142 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu NR 66 TC 19 Z9 20 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD AUG 6 PY 2007 VL 46 IS 16 BP 6621 EP 6631 DI 10.1021/ic7006843 PG 11 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 194LF UT WOS:000248345200053 PM 17625838 ER PT J AU Caravan, P Parigi, G Chasse, JM Cloutier, NJ Ellison, JJ Lauffer, RB Luchinat, C McDermid, SA Spiller, M McMurry, TJ AF Caravan, Peter Parigi, Giacomo Chasse, Jaclyn M. Cloutier, Normand J. Ellison, Jeffrey J. Lauffer, Randall B. Luchinat, Claudio McDermid, Sarah A. Spiller, Marga McMurry, Thomas J. TI Albumin binding, relaxivity, and water exchange kinetics of the diastereoisomers of MS-325, a gadolinium(III)-based magnetic resonance angiography contrast agent SO INORGANIC CHEMISTRY LA English DT Article ID AORTOILIAC OCCLUSIVE DISEASE; NUCLEAR-SPIN RELAXATION; H-1 NMRD PROFILES; MR-ANGIOGRAPHY; PARAMAGNETIC-COMPLEXES; GD3+ COMPLEXES; PHASE-III; O-17 NMR; DYNAMICS; DTPA AB The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 consists of two slowly interconverting diastereoisomers, A and B (65:35 ratio), which can be isolated at pH > 8.5 (Tyeklar, Z.; Dunham, S. U.; Midelfort, K.; Scott, D. M.; Sajiki, H.; Ong, K.; Lauffer, R. B.; Caravan, P.; McMurry, T. J. Inorg. Chem. 2007, 46, 6621-6631). MS-325 binds to human serum albumin (HSA) in plasma resulting in an extended plasma half-life, retention of the agent within the blood compartment, and an increased relaxation rate of water protons in plasma. Under physiological conditions (37 degrees C, pH 7.4, phosphate buffered saline (PBS), 4.5% HSA, 0.05 mM complex), there is no statistical difference in HSA affinity or relaxivity between the two isomers ( A 88.6 +/- 0.6% bound, r(1) = 42.0 +/- 1.0 mM(-1) s(-1) at 20 MHz; B 90.2 +/- 0.6% bound, r(1) = 38.3 +/- 1.0 mM(-1) s(-1) at 20 MHz; errors represent 1 standard deviation). At lower temperatures, isomer A has a higher relaxivity than isomer B. The water exchange rates in the absence of HSA at 298 K, k (298)(A) = 5.9 +/- 2.8 x 10(6) s(-1), k (298)(B) = 3.2 +/- 1.8 x 10(6) s(-1), and heats of activation, Delta H-A(double dagger) = 56 +/- 8 kJ/mol, Delta H-B(double dagger) = 59 +/- 11 kJ/mol, were determined by variable-temperature O-17 NMR at 7.05 T. Proton nuclear magnetic relaxation dispersion (NMRD) profiles were recorded over the frequency range of 0.01-50 MHz at 5, 15, 25, and 35 degrees C in a 4.5% HSA in PBS solution for each isomer (0.1 mM). Differences in the relaxivity in HSA between the two isomers could be attributed to the differing water exchange rates. C1 Massachusetts Gen Hosp East, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EPIX Pharmaceut, Cambridge, MA 02142 USA. CERM, I-50019 Sesto Fiorentino, Italy. Univ Florence, Dept Agr Biotechnol, I-50019 Sesto Fiorentino, Italy. New York Med Coll, Dept Radiol, Valhalla, NY 10595 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp East, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu OI Parigi, Giacomo/0000-0002-1989-4644; Luchinat, Claudio/0000-0003-2271-8921 NR 32 TC 91 Z9 93 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 EI 1520-510X J9 INORG CHEM JI Inorg. Chem. PD AUG 6 PY 2007 VL 46 IS 16 BP 6632 EP 6639 DI 10.1021/ic700686k PG 8 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 194LF UT WOS:000248345200054 PM 17625839 ER PT J AU von Boehmer, H AF von Boehmer, Harald TI Oral tolerance: is it all retinoic acid? SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID REGULATORY T-CELLS; DENDRITIC CELLS; IN-VIVO; FOXP3; MECHANISMS; INDUCTION; ANTIGEN AB Oral tolerance has been argued to depend on "special" presentation of antigen in the gut. New studies support this idea by showing that the catalysis of vitamin A into retinoic acid (RA) in gut-associated dendritic cells (DCs) enhances the transforming growth factor (TGF)-beta-dependent conversion of naive T cells into regulatory T (T reg) cells and also directs T reg cell homing to the gut. These results reveal new tolerance mechanisms that will aid the use of T reg cells in the clinic. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 19 TC 66 Z9 72 U1 0 U2 0 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 AUG 6 PY 2007 VL 204 IS 8 BP 1737 EP 1739 DI 10.1084/jem.20071251 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700004 PM 17620364 ER PT J AU Sun, CM Hall, JA Blank, RB Bouladoux, N Oukka, M Mora, JR Belkaid, Y AF Sun, Cheng-Ming Hall, Jason A. Blank, Rebecca B. Bouladoux, Nicolas Oukka, Mohamed Mora, J. Rodrigo Belkaid, Yasmine TI Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; ORAL TOLERANCE; ANTIGEN; INDUCTION; ACTIVATION; EXPRESSION; SELECTION; EFFECTOR; IMMUNITY AB To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3(+) T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4(+) T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ-derived Ill This enhanced conversion by LpDCs was dependent on TGF-beta and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion. C1 NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brigham Womens Hosp, Ctr Neurol Dis, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Intramural NIH HHS NR 36 TC 1052 Z9 1087 U1 3 U2 43 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 AUG 6 PY 2007 VL 204 IS 8 BP 1775 EP 1785 DI 10.1084/jem.20070602 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700009 PM 17620362 ER PT J AU O'Neil, J Grim, J Strack, P Rao, S Tibbitts, D Winter, C Hardwick, J Welcker, M Meijerink, JP Pieters, R Draetta, G Sears, R Clurman, BE Look, AT AF O'Neil, Jennifer Grim, Jonathan Strack, Peter Rao, Sudhir Tibbitts, Deanne Winter, Christopher Hardwick, James Welcker, Markus Meijerink, Jules P. Pieters, Rob Draetta, Giulio Sears, Rosalie Clurman, Bruce E. Look, A. Thomas TI FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID REGULATES C-MYC; F-BOX PROTEIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; UBIQUITIN LIGASE; CYCLIN-E; CHROMOSOMAL INSTABILITY; MAMMARY TUMORIGENESIS; OVARIAN-CANCER; EXPRESSION; MICE AB gamma-secretase inhibitors (GSIs) can block NOTCH receptor signaling in vitro and therefore offer an attractive targeted therapy for tumors dependent on deregulated NOTCH activity. To clarify the basis for GSI resistance in T cell acute lymphoblastic leukemia (T-All we studied T-ALL cell lines with constitutive expression of the NOTCH intracellular domain (NICD), but that lacked C-terminal truncating mutations in NOTCH1. Each of the seven cell lines examined and 7 of 81 (8.6%) primary T-ALL samples harbored either a mutation or homozygous deletion of the gene FBW7, a ubiquitin ligase implicated in NICD turnover. Indeed, we show that I'll mutants cannot bind to the NICD and define the phosphodegron region of the NICD required for Ill binding. Although the mutant forms of Ill were still able to bind to MYC, they do not target it for degradation, suggesting that stabilization of both NICD and its principle downstream target, Ill may contribute to transformation in leukemias with FBW7 mutations. In addition, we show that all seven leukemic cell lines with FBW7 mutations were resistant to the MRK-003 GSI. Most of these resistant lines also failed to down-regulate the mRNA levels of the NOTCH targets MYC and DELTEX1 after treatment with MRK-003, implying that residual NOTCH signaling in T-ALLs with FBW7 mutations contributes to GSI resistance. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Merck Res Labs, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. Merck Res Labs, West Point, PA 19486 USA. Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, NL-3000 CB Rotterdam, Netherlands. Childrens Hosp, Div Hematol, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM bclurman@fhcrc.org; Thomas_Look@dfci.harvard.edu RI Meijerink, Jules/D-4393-2017; OI Meijerink, Jules/0000-0002-6860-798X; Welcker, Markus/0000-0001-6723-4790 FU NCI NIH HHS [R01 CA084069, 1K08CA109124-01A2, K08 CA109124, R01 CA102742, R01CA102742, R01CA84069]; NHLBI NIH HHS [P01 HL084205] NR 58 TC 337 Z9 339 U1 2 U2 26 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 AUG 6 PY 2007 VL 204 IS 8 BP 1813 EP 1824 DI 10.1084/jem.20070876 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700012 PM 17646409 ER PT J AU Benarafa, C Priebe, GP Remold-O'Donnell, E AF Benarafa, Charaf Priebe, Gregory P. Remold-O'Donnell, Eileen TI The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYSTIC-FIBROSIS; ELASTASE INHIBITOR; ALVEOLAR MACROPHAGES; HOST-DEFENSE; CATHEPSIN-G; CLEARANCE; RECEPTOR; CELLS; INFLAMMATION; MICE AB Neutrophil serine proteases (NSPs; elastase, cathepsin G, and proteinase-3) directly kill invading microbes. However, excess NSPs in the lungs play a central role in the pathology of inflammatory pulmonary disease. We show that serpinb1, an efficient inhibitor of the three NSPs, preserves cell and molecular components responsible for host defense against Pseudomonas aeruginosa. On infection, wild-type (WT) and serpinb1-deficient mice mount similar early responses, including robust production of cytokines and chemokines, recruitment of neutrophils, and initial containment of bacteria. However, serpinb1(-/-) mice have considerably increased mortality relative to WT mice in association with late-onset failed bacterial clearance. We found that serpinb I-deficient neutrophils recruited to the lungs have an intrinsic defect in survival accompanied by release of neutrophil protease activity, sustained inflammatory cytokine production, and proteolysis of the collectin surfactant protein-D (SP-D). Coadministration of recombinant SERPINB1 with the P. aeruginosa inoculum normalized bacterial clearance in serpinb1(-/-) mice. Thus, regulation of pulmonary innate immunity by serpinb1 is nonredundant and is required to protect two key components, the neutrophil and SP-D, from NSP damage during the host response to infection. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia Crit Care Med, Boston, MA 02115 USA. Childrens Hosp, Dept Med Infect Dis, Boston, MA 02115 USA. RP Benarafa, C (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM benarafa@cbr.med.harvard.edu OI Benarafa, Charaf/0000-0002-2049-7769 FU NHLBI NIH HHS [HL66548, R01 HL066548, R21 HL079423, R21 HL79423]; NIAID NIH HHS [K08 AI050036, K08 AI50036] NR 40 TC 65 Z9 66 U1 1 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 AUG 6 PY 2007 VL 204 IS 8 BP 1901 EP 1909 DI 10.1084/jem.20070494 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700019 PM 17664292 ER PT J AU Wu, HJ Sawaya, H Binstadt, B Brickelmaier, M Blasius, A Gorelik, L Mahmood, U Weissleder, R Carulli, J Benoist, C Mathis, D AF Wu, Hsin-Jung Sawaya, Heloisa Binstadt, Bryce Brickelmaier, Margot Blasius, Amanda Gorelik, Leonid Mahmood, Umar Weissleder, Ralph Carulli, John Benoist, Christophe Mathis, Diane TI Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; RECOMBINANT INTERFERON-GAMMA; NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTORS; RHEUMATOID-ARTHRITIS; DENDRITIC CELLS; BACTERIAL-DNA; IN-VIVO; DIFFERENTIAL REGULATION; ADAPTIVE IMMUNITY AB Unmethylated CpG-oligodeoxynucleotides (ODNs) are generally thought of as potent adjuvants with considerable therapeutic potential to enhance immune responses against microbes and tumors. Surprisingly, certain so-called stimulatory CpG-ODNs strongly inhibited the effector phase of inflammatory arthritis in the K/BxN serum transfer system, either preventively or therapeutically. Also unexpected was that the inhibitory influence did not depend on the adaptive immune system cells mobilized in an immunostimulatory context. Instead, they relied on cells of the innate immune system, specifically on cross talk between CD8 alpha(+) dendritic cells and natural killer cells, resulting in suppression of neutrophil recruitment to the joint, orchestrated through interleukin-12 and interferon-gamma. These findings highlight potential applications of CpG-ODNs and downstream molecules as antiinflarnmatory agents. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Rheumatol Program, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Biogen Idec Inc, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02114 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63101 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. EM cbdm@joslin.harvard.edu RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 FU NCI NIH HHS [R24 CA 92782, R24 CA092782]; NIAID NIH HHS [P01 AI054904, P01 AI54904] NR 63 TC 56 Z9 58 U1 1 U2 4 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 AUG 6 PY 2007 VL 204 IS 8 BP 1911 EP 1922 DI 10.1084/jem.20070285 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 199XE UT WOS:000248727700020 PM 17646407 ER PT J AU Matsui, T Ingelsson, M Fukumoto, H Ramasamy, K Kowa, H Frosch, MP Irizarry, MC Hyman, BT AF Matsui, Toshifumi Ingelsson, Martin Fukumoto, Hiroaki Ramasamy, Karunya Kowa, Hisatomo Frosch, Matthew P. Irizarry, Michael C. Hyman, Bradley T. TI Expression of APP pathway mRNAs and proteins in Alzheimer's disease SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; APP; A beta; Kunitz; microglia ID AMYLOID PRECURSOR-PROTEIN; RECEPTOR-RELATED PROTEIN; BRAIN A-BETA; APOLIPOPROTEIN-E; DOWN-SYNDROME; ENDOCYTIC PATHWAY; DENSITY; CELLS; PCR; SECRETASE AB In both trisomy 21 and rare cases of triplication of amyloid precursor protein (APP) Alzheimer's disease (AD) pathological changes are believed to be secondary to increased expression of APP. We hypothesized that sporadic AD may also be associated with changes in transcription of APP or its metabolic partners. To address this issue, temporal neocortex of 27 AD and 21 non-demented control brains was examined to assess mRNA levels of APP isoforms (total APP, APP containing the Kunitz protease inhibitor domain [APP-KPI] and APP770) and APP metabolic enzymatic partners (the APP cleaving enzymes beta-secretase [BACE] and presenilin-1 [PS- 1], and putative clearance molecules, low-density lipoprotein receptor protein [LRP] and apolipoprotein E [apoE]). Furthermore, we evaluated how changes in APP at the mRNA level affect the amount of Tris buffer extractable APP protein and A beta 40 and 42 peptides in AD and control brains. As assessed by quantitative PCR, APP-KPI (p=0.007), APP770 (p=0.004), PS-1 (p = 0.004), LRP (p = 0.003), apoE (p = 0.0002) and GFAP (p < 0.0001) mRNA levels all increased in AD, and there was a shift from APP695 (a neuronal isoform) towards KPI containing isoforms that are present in glia as well. APP-KPI mRNA levels correlated with soluble APP alpha -KPI protein (sAPP alpha -KPI) levels measured by ELISA (T= 0.33, p = 0.015 by Kendall's rank correlation); in turn, soluble APP alpha-KPI protein levels positively correlated with Tris -extractable, soluble A beta 40 (p=0.046) and 42 levels (p=0.007). The ratio of soluble APP alpha-KPI protein levels to total APP protein increased in AD, and also correlated with GFAP protein levels in AD. These results suggest that altered transcription of APP in AD is proportionately associated with A beta peptide, may occur in the context of gliosis, and may contribute to A beta deposition in sporadic AD. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. Univ Uppsala, Uppsala, Sweden. Massachusetts Gen Hosp, CS Kubik Lab Neurppathol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIA NIH HHS [AG08487, P50 AG05134] NR 46 TC 78 Z9 81 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 3 PY 2007 VL 1161 BP 116 EP 123 DI 10.1016/j.brainres.2007.05.050 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 202GZ UT WOS:000248891300013 PM 17586478 ER PT J AU Wang, QB Li, W Liu, XS Carroll, JS Janne, OA Keeton, EK Chinnaiyan, AM Pienta, KJ Brown, M AF Wang, Qianben Li, Wei Liu, X. Shirley Carroll, Jason S. Janne, Olli A. Keeton, Erika Krasnickas Chinnaiyan, Arul M. Pienta, Kenneth J. Brown, Myles TI A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth SO MOLECULAR CELL LA English DT Article ID GENE-EXPRESSION; NUCLEAR RECEPTORS; RECRUITMENT; CELLS; COMPLEX; PHOSPHODIESTERASE; IDENTIFICATION; PROLIFERATION; MECHANISM; ENHANCER AB Androgen receptor (AR) is a ligand -dependent transcription factor that plays a key role in prostate cancer. Little is known about the nature of AR cis-regulatory sites in the human genome. We have mapped the AR binding regions on two chromosomes in human prostate cancer cells by combining chromatin immunoprecipitation (ChIP) with tiled oligonucleotide microarrays. We find that the majority of AR binding regions contain noncanonical AR-responsive elements (AREs). Importantly, we identify a noncanonical ARE as a cis-regulatory target of AR action in TMPRSS2, a gene fused to ETS transcription factors in the majority of prostate cancers. In addition, through the presence of enriched DNA-binding motifs, we find other transcription factors including GATA2 and Octl that cooperate in mediating the androgen response. These collaborating factors, together with AR, form a regulatory hierarchy that governs androgendependent gene expression and prostate cancer growth and offer potential new opportunities for therapeutic intervention. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Helsinki, Inst Biomed Physiol, FI-00014 Helsinki, Finland. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Li, Wei/A-8544-2009; Wang, Qianben/E-4267-2011; Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [P50 CA090381, P50 CA 69568, P50 CA 90381, P50 CA069568]; NHGRI NIH HHS [R01 HG004069, R01 HG004069-01, R01 HG004069-02] NR 40 TC 345 Z9 354 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 3 PY 2007 VL 27 IS 3 BP 380 EP 392 DI 10.1016/j.molcel.2007.05.041 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 201HZ UT WOS:000248823400004 PM 17679089 ER PT J AU Kioussis, D Georgopoulos, K AF Kioussis, Dimitris Georgopoulos, Katia TI Perspective - Epigenetic flexibility underlying lineage choices in the adaptive immune system SO SCIENCE LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; B-CELLS; CHROMATIN; LYMPHOCYTE; EXPRESSION; COMPLEXES; DIVISION; IKAROS; GENES; CD4 AB Although fundamental models have emerged in recent years describing how chromatin and transcription regulation interface with one another in the developing immune system, the order of events and their biological impact are still being resolved. Recent advances have provided a flexible, rather than static, view of chromatin regulation to reveal how both positive and negative forces work concomitantly to establish specific chromatin structures and regulate gene expression. The challenge will now be to explore new epigenetic models and validate them during lymphocyte development, with the ultimate goal of unraveling the long-sought mechanisms that support the emerging complexity of the adaptive immune response. C1 Natl Inst Med Res, MRC, London NW7 1AA, England. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Kioussis, D (reprint author), Natl Inst Med Res, MRC, Ridgeway, London NW7 1AA, England. EM dkiouss@nimr.mrc.ac.uk FU Medical Research Council [MC_U117512796] NR 31 TC 18 Z9 18 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 AUG 3 PY 2007 VL 317 IS 5838 BP 620 EP 622 DI 10.1126/science.1143777 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 196PL UT WOS:000248494400032 PM 17673651 ER PT J AU Meyerson, M AF Meyerson, Matthew TI Cancer - Broken genes in solid tumours SO NATURE LA English DT Editorial Material ID LUNG-CANCER; MUTATIONS; GEFITINIB; THERAPY; KINASE; FUSION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 12 TC 10 Z9 10 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 2 PY 2007 VL 448 IS 7153 BP 545 EP 546 DI 10.1038/448545a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195XV UT WOS:000248446700030 PM 17671492 ER PT J AU Mikkelsen, TS Ku, MC Jaffe, DB Issac, B Lieberman, E Giannoukos, G Alvarez, P Brockman, W Kim, TK Koche, RP Lee, W Mendenhall, E O'Donovan, A Presser, A Russ, C Xie, XH Meissner, A Wernig, M Jaenisch, R Nusbaum, C Lander, ES Bernstein, BE AF Mikkelsen, Tarjei S. Ku, Manching Jaffe, David B. Issac, Biju Lieberman, Erez Giannoukos, Georgia Alvarez, Pablo Brockman, William Kim, Tae-Kyung Koche, Richard P. Lee, William Mendenhall, Eric O'Donovan, Aisling Presser, Aviva Russ, Carsten Xie, Xiaohui Meissner, Alexander Wernig, Marius Jaenisch, Rudolf Nusbaum, Chad Lander, Eric S. Bernstein, Bradley E. TI Genome-wide maps of chromatin state in pluripotent and lineage-committed cells SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; HISTONE LYSINE METHYLATION; DEVELOPMENTAL REGULATORS; DNA METHYLATION; GENE-EXPRESSION; NONCODING RNAS; MOUSE; POLYCOMB; TRANSCRIPTION; DIFFERENTIATION AB We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations. C1 Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lander, ES (reprint author), Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. EM lander@broad.mit.edu; bbernstein@partners.org RI Mikkelsen, Tarjei/A-1306-2007; Lieberman-Aiden, Erez/A-2908-2010; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Mendenhall, Eric/0000-0002-7395-6295 FU NCI NIH HHS [T32 CA009216]; NIGMS NIH HHS [R01 GM078986-01, R01 GM078986] NR 48 TC 2277 Z9 2341 U1 29 U2 200 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 2 PY 2007 VL 448 IS 7153 BP 553 EP U2 DI 10.1038/nature06008 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195XV UT WOS:000248446700035 PM 17603471 ER PT J AU Tomlins, SA Laxman, B Dhanasekaran, SM Helgeson, BE Cao, XH Morris, DS Menon, A Jing, XJ Cao, Q Han, B Yu, JD Wang, L Montie, JE Rubin, MA Pienta, KJ Roulston, D Shah, RB Varambally, S Mehra, R Chinnaiyan, AM AF Tomlins, Scott A. Laxman, Bharathi Dhanasekaran, Saravana M. Helgeson, Beth E. Cao, Xuhong Morris, David S. Menon, Anjana Jing, Xiaojun Cao, Qi Han, Bo Yu, Jindan Wang, Lei Montie, James E. Rubin, Mark A. Pienta, Kenneth J. Roulston, Diane Shah, Rajal B. Varambally, Sooryanarayana Mehra, Rohit Chinnaiyan, Arul M. TI Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer SO NATURE LA English DT Article ID HIGH-FREQUENCY; CELL-LINES; EXPRESSION; TMPRSS2-ERG; TRANSLOCATIONS; IDENTIFICATION; MECHANISMS; RELEVANT; PATHWAYS; LEUKEMIA AB Recently, we identified recurrent gene fusions involving the 59 untranslated region of the androgen-regulated gene TMPRSS2 and the ETS (E26 transformation-specific) family genes ERG, ETV1 or ETV4 in most prostate cancers(1,2). Whereas TMPRSS2 ERG fusions are predominant, fewer TMPRSS2-ETV1 cases have been identified than expected on the basis of the frequency of high (outlier) expression of ETV1 (refs 3-13). Here we explore the mechanism of ETV1 outlier expression in human prostate tumours and prostate cancer cell lines. We identified previously unknown 59 fusion partners in prostate tumours with ETV1 outlier expression, including untranslated regions from a prostate-specific androgen-induced gene (SLC45A3) and an endogenous retroviral element (HERV-K_22q11.23), a prostate-specific androgen-repressed gene (C15orf21), and a strongly expressed housekeeping gene (HNRPA2B1). To study aberrant activation of ETV1, we identified two prostate cancer cell lines, LNCaP and MDA-PCa 2B, that had ETV1 outlier expression. Through distinct mechanisms, the entire ETV1 locus (7p21) is rearranged to a 1.5-megabase prostate-specific region at 14q13.3-14q21.1 in both LNCaP cells (cryptic insertion) and MDA- PCa 2B cells (balanced translocation). Because the common factor of these rearrangements is aberrant ETV1 overexpression, we recapitulated this event in vitro and in vivo, demonstrating that ETV1 overexpression in benign prostate cells and in the mouse prostate confers neoplastic phenotypes. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 59 fusion partners may have implications for the anti-androgen treatment of advanced prostate cancer. C1 Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Dept Pathol, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Cao, Qi/A-5517-2010; Pienta, Kenneth/E-7679-2015; OI Cao, Qi/0000-0002-5140-3681; Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 NR 34 TC 440 Z9 450 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 2 PY 2007 VL 448 IS 7153 BP 595 EP U9 DI 10.1038/nature06024 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195XV UT WOS:000248446700044 PM 17671502 ER PT J AU Woolf, CJ Ma, QF AF Woolf, Clifford J. Ma, Qiufu TI Nociceptors-noxious stimulus detectors SO NEURON LA English DT Review ID DORSAL-ROOT-GANGLIA; INFLAMMATORY PAIN HYPERSENSITIVITY; PRIMARY SENSORY NEURONS; PRIMARY AFFERENT NOCICEPTOR; SODIUM-CHANNEL NA(V)1.9; NERVE GROWTH-FACTOR; TRP ION CHANNELS; CAPSAICIN-RECEPTOR; NEUROPATHIC PAIN; SPINAL-CORD AB Clinical pain is a serious public health issue. Treatment of pain-related suffering requires knowledge of how pain signals are initially interpreted and subsequently transmitted and perpetuated. This review article is one of three reviews in this issue of Neuron that address our understanding of the pain process and possible solutions to the problem from both cellular- and systems-level viewpoints. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. EM cwoolf@partners.org NR 115 TC 318 Z9 330 U1 8 U2 50 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG 2 PY 2007 VL 55 IS 3 BP 353 EP 364 DI 10.1016/j.neuron.2007.07.016 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 199QT UT WOS:000248711000005 PM 17678850 ER PT J AU Wu, D Zhau, HE Huang, WC Iqbal, S Habib, FK Sartor, O Cvitanovic, L Marshall, FF Xu, Z Chung, LWK AF Wu, D. Zhau, H. E. Huang, W-C Iqbal, S. Habib, F. K. Sartor, O. Cvitanovic, L. Marshall, F. F. Xu, Z. Chung, L. W. K. TI cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: implication in human prostate cancer bone metastasis SO ONCOGENE LA English DT Article DE prostate cancer; bone metastasis; EMT; CREB; VEGF; HIF ID EPITHELIAL-MESENCHYMAL TRANSITION; HYPOXIA-INDUCIBLE FACTOR-1; GENOME-WIDE ANALYSIS; TRANSCRIPTIONAL REGULATION; TUMOR PROGRESSION; CELLS; CREB; ACTIVATION; GENE; VEGF AB Aberrant expression of vascular endothelial growth factor (VEGF) is associated with human prostate cancer (PCa) metastasis and poor clinical outcome. We found that both phosphorylation of cyclic AMP- responsive element- binding protein (CREB) and VEGF levels were significantly elevated in patient bone metastatic PCa specimens. A PCa ARCaP progression model demonstrating epithelial- to-mesenchymal transition exhibited increased CREB phosphorylation and VEGF expression as ARCaP cells became progressively more mesenchymal and bone- metastatic. Activation of CREB induced, whereas inhibition of CREB blocked, VEGF expression in ARCaP cells. CREB may regulate VEGF transcription via a hypoxia- inducible factor- dependent mechanism in normoxic conditions. Activation of CREB signaling is involved in the coordinated regulation of VEGF and may pre- dispose to PCa bone metastasis. C1 Emory Univ, Sch Med, Mol Urol & Therapeut Program, Dept Urol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. Western Gen Hosp, Sch Mol & Clin Med, Div Oncol, Prostate Res Grp, Edinburgh EH4 2XU, Midlothian, Scotland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. LSU, Ctr Hlth Sci, Stanley Scott Canc Ctr, New Orleans, LA USA. RP Wu, D (reprint author), Emory Univ, Sch Med, Mol Urol & Therapeut Program, Dept Urol, 1365-B Clifton Rd,Suite 5100, Atlanta, GA 30322 USA. EM dwu2@emory.edu; lwchung@emory.edu OI Huang, William/0000-0001-5261-0650 FU NCI NIH HHS [PC040260, 1 P01 CA098912, 1 R01 CA108468, PC060566]; NIGMS NIH HHS [5 P20 GM072069] NR 38 TC 71 Z9 74 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 2 PY 2007 VL 26 IS 35 BP 5070 EP 5077 DI 10.1038/sj.onc.1210316 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 196MT UT WOS:000248487400005 PM 17310988 ER PT J AU Shin, EK Jupiter, JB AF Shin, E. K. Jupiter, J. B. TI Current concepts in the management of distal radius fractures SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA LA English DT Review ID DISPLACED INTRAARTICULAR FRACTURES; INTERNAL-FIXATION; OPEN REDUCTION; EXTERNAL FIXATION; YOUNG-ADULTS; WRIST; PLATE; END; VOLAR; HAND AB The treatment of fractures at the distal end of the radius continues to challenge orthopaedic and upper extremity surgeons. As our understanding of the injury mechanism and local anatomy continues to improve, so too have our surgical techniques in helping patients regain functional use of the injured extremity. The purpose of this maniscript is to review the treatment methods available for distal radius fracture management. C1 [Jupiter, J. B.] Massachusetts Gen Hosp, Hand & Upper Exterm Serv, Boston, MA 02114 USA. [Shin, E. K.] Brigham & Womens Hosp, Hand & Upper Exterm Serv, Boston, MA 02115 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Hand & Upper Exterm Serv, 55 Fruit St,YAW-2-2C, Boston, MA 02114 USA. NR 33 TC 24 Z9 24 U1 1 U2 2 PU GALEN SRO PI PRAGUE 5 PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC SN 0001-5415 J9 ACTA CHIR ORTHOP TR PD AUG PY 2007 VL 74 IS 4 BP 233 EP 246 PG 14 WC Orthopedics SC Orthopedics GA 278BE UT WOS:000254257700001 PM 17877939 ER PT J AU Louis, DN Ohgaki, H Wiestler, OD Cavenee, WK Burger, PC Jouvet, A Scheithauer, BW Kleihues, P AF Louis, David N. Ohgaki, Hiroko Wiestler, Otmar D. Cavenee, Webster K. Burger, Peter C. Jouvet, Anne Scheithauer, Bernd W. Kleihues, Paul TI The 2007 WHO classification of tumours of the central nervous system SO ACTA NEUROPATHOLOGICA LA English DT Review ID SPINDLE-CELL-ONCOCYTOMA; DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR; FORMING GLIONEURONAL TUMOR; NEUROPIL-LIKE ISLANDS; OLIGODENDROGLIAL COMPONENT; MELANOTIC MEDULLOBLASTOMA; MEDULLOMYOBLASTOMA; ADENOHYPOPHYSIS; DIFFERENTIATION; 4TH-VENTRICLE AB The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO 'Blue Book', the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide. C1 Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Int Agcy Res Canc, F-69008 Lyon, France. German Canc Res Ctr, D-69120 Heidelberg, Germany. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21210 USA. Natl Hosp Neurol & Neurosurg, E Pathol & Neuropathol Ctr, F-69003 Lyon, France. Mayo Clin, Dept Pathol & Lab Med, Rochester, MN 55905 USA. RP Kleihues, P (reprint author), Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. EM paul.kleihues@usz.ch RI champier, jacques/B-4160-2012; Waha, Andreas/J-2950-2014 NR 52 TC 4125 Z9 4533 U1 35 U2 266 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD AUG PY 2007 VL 114 IS 2 BP 97 EP 109 DI 10.1007/s00401-007-0243-4 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 190GK UT WOS:000248046800001 PM 17618441 ER PT J AU Koeppen, AH Michael, SC Knutson, MD Haile, DJ Qian, J Levi, S Santambrogio, P Garrick, MD Lamarche, JB AF Koeppen, Arnulf H. Michael, Susan C. Knutson, Mitchell D. Haile, David J. Qian, Jiang Levi, Sonia Santambrogio, Paolo Garrick, Michael D. Lamarche, Jacques B. TI The dentate nucleus in Friedreich's ataxia: the role of iron-responsive proteins SO ACTA NEUROPATHOLOGICA LA English DT Article DE Friedreich's ataxia; atrophy; dentate nucleus; ferritin; ferroportin; iron; synapses ID SUPERFICIAL SIDEROSIS; HEREDITARY ATAXIAS; BRAIN; TRANSPORTER; FERROPORTIN; FERRITIN; CARDIOMYOPATHY; SYSTEM AB Frataxin deficiency in Friedreich's ataxia (FRDA) causes cardiac, endocrine, and nervous system manifestations. Frataxin is a mitochondrial protein, and adequate amounts are essential for cellular iron homeostasis. The main histological lesion in the brain of FRDA patients is neuronal atrophy and a peculiar proliferation of synaptic terminals in the dentate nucleus termed grumose degeneration. This cerebellar nucleus may be especially susceptible to FRDA because it contains abundant iron. We examined total iron and selected iron-responsive proteins in the dentate nucleus of nine patients with FRDA and nine normal controls by biochemical and microscopic techniques. Total iron (1.53 +/- 0.53 mu mol/g wet weight) and ferritin (206.9 +/- 46.6 mu g/g wet weight) in FRDA did not significantly differ from normal controls (iron: 1.78 +/- 0.88 mu mol/g; ferritin: 210.9 +/- 9.0 mu g/g) but Western blots exhibited a shift to light ferritin subunits. Immunocytochemistry of the dentate nucleus revealed loss of juxtaneuronal ferritin-containing oligodendroglia and prominent ferritin immunoreactivity in microglia and astrocytes. Mitochondrial ferritin was not detectable by immunocytochemistry. Stains for the divalent metal transporter 1 confirmed neuronal loss while endothelial cells reacting with antibodies to transferrin receptor 1 protein showed crowding of blood vessels due to collapse of the normal neuropil. Regions of grumose degeneration were strongly reactive for ferroportin. Purkinje cell bodies, their dendrites and axons, were also ferroportin-positive, and it is likely that grumose degeneration is the morphological manifestation of mitochondrial iron dysmetabolism in the terminals of corticonuclear fibers. Neuronal loss in the dentate nucleus is the likely result of trans-synaptic degeneration. C1 Stratton VA Med Ctr, Albany, NY 12208 USA. Vet Affairs Med Ctr, Res, Albany, NY USA. Vet Affairs Med Ctr, Albany, NY USA. Vet Affairs Med Ctr, Pathol Serv, Albany, NY USA. Albany Med Coll, Dept Neurol & Pathol, Albany, NY 12208 USA. Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. Univ Texas, Vet Affairs Med Ctr, Hlth Sci Ctr, San Antonio, TX USA. Ist Sci San Raffaele, Milan, Italy. Vita Salute San Rafaelle Univ, Milan, Italy. SUNY Buffalo, Dept Biochem, Buffalo, NY USA. Univ Sherbrooke, Ctr Hosp, Sherbrooke, PQ J1K 2R1, Canada. RP Koeppen, AH (reprint author), Stratton VA Med Ctr, 113 Holland Ave, Albany, NY 12208 USA. EM arnulf.koeppen@va.gov RI Levi, Sonia/A-3161-2015 OI Levi, Sonia/0000-0002-5092-0847 FU NIDDK NIH HHS [DK065064]; PHS HHS [R01DLK59794] NR 33 TC 69 Z9 71 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD AUG PY 2007 VL 114 IS 2 BP 163 EP 173 DI 10.1007/s00401-007-0220-y PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 190GK UT WOS:000248046800007 PM 17443334 ER PT J AU Biederman, J Petty, CR Fried, R Doyle, AE Spencer, T Seidman, LJ Gross, L Poetzl, K Faraone, SV AF Biederman, J. Petty, C. R. Fried, R. Doyle, A. E. Spencer, T. Seidman, L. J. Gross, L. Poetzl, K. Faraone, S. V. TI Stability of executive function deficits into young adult years: a prospective longitudinal follow-up study of grown up males with ADHD SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE executive functions; attention deficit-hyperactivity disorder; neuropsychology; stability ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HYPERACTIVITY DISORDER; CHILDREN; PERFORMANCE; NEUROPSYCHOLOGY; METAANALYSIS; ADOLESCENTS; IMPACT AB Objective: Although individuals with attention deficit-hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions that greatly increase the morbidity of the disorder, all available information on the subject is cross sectional. Method: Males (n = 85) 9-22 years with ADHD followed over 7 years into young adulthood were assessed on measures of sustained attention/vigilance, planning and organization, response inhibition, set shifting and categorization, selective attention and visual scanning, verbal and visual learning, and memory. A binary definition of executive function deficits (EFDs) was defined based on a subject manifesting at least two abnormal tests 1.5 standard deviations from controls. Results: The majority of subjects maintained EFDs over time (kappa: 0.41, P < 0.001; sensitivity: 55%, specificity: 85%, positive predictive value: 69%, and negative predictive value: 75%). Conclusion: Considering the morbidity of EFDs, these findings stress the importance of their early recognition for prevention and early intervention strategies. EFDs are stable over time. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Program, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD-36317-07] NR 38 TC 88 Z9 91 U1 1 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD AUG PY 2007 VL 116 IS 2 BP 129 EP 136 DI 10.1111/j.1600-0447.2007.01008.x PG 8 WC Psychiatry SC Psychiatry GA 190VE UT WOS:000248087900008 PM 17650275 ER PT J AU O'Farrell, TJ Murphy, M Alter, J Fals-Stewart, W AF O'Farrell, Timothy J. Murphy, Marie Alter, Jane Fals-Stewart, William TI Brief family treatment intervention to promote aftercare among male substance abusing patients in inpatient detoxification: A quasi-experimental pilot study SO ADDICTIVE BEHAVIORS LA English DT Article; Proceedings Paper CT Annual-Research-Society-on-Alcoholism-Scientific Meeting CY JUN, 2001 CL Montreal, CANADA SP Annual Res Soc Alcoholism Sci DE family therapy; detoxification ID ALCOHOLISM AB We developed a brief family treatment (BFT) intervention for substance abusing patients in inpatient detoxification to promote aftercare treatment post-detox. BFT consisted of meeting with the patient and a family member (spouse or parent) with whom the patient lived to review and recommend potential aftercare plans for the patient. A phone conference was used when logistics prevented an in-person family meeting. Results indicated that male substance abusing patients who received BFT (N= 14), as compared with a matched treatment as usual (TAU) comparison group (N= 14) that did not, showed a trend toward being more likely to enter an aftercare program and to attend more days of aftercare in the 3 months after detoxification. The magnitude of these differences favoring BFT over TAU was midway between a medium and a large effect size. Days using alcohol or drugs in the 3 months after detox were lower for treatment-exposed BFT patients who had an in-person family meeting than TAU counterparts (trend, medium effect), and for patients who entered aftercare regardless of treatment condition (significant large effect). (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, VAMC, Dept Psychiat,VA Boston Healthcare Syst,Families, Brockton, MA 02301 USA. Univ Rochester, Dept Psychiat, Rochester, NY USA. RP O'Farrell, TJ (reprint author), Harvard Univ, Sch Med, VAMC, Dept Psychiat,VA Boston Healthcare Syst,Families, 940 Belmont St, Brockton, MA 02301 USA. EM timothy_ofarrell@hms.harvard.edu FU NIAAA NIH HHS [K02 AA000234, K02 AA000234-09, K02AA00234, R21 AA011735, R21AA11735, R21 AA011735-02] NR 18 TC 15 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD AUG PY 2007 VL 32 IS 8 BP 1681 EP 1691 DI 10.1016/j.addbeh.2006.12.001 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 179PS UT WOS:000247302800012 PM 17223279 ER PT J AU Forcehimes, AA Tonigan, JS Miller, WR Kenna, GA Baer, JS AF Forcehimes, Alyssa A. Tonigan, J. Scott Miller, William R. Kenna, George A. Baer, John S. TI Psychometrics of the Drinker Inventory of Consequences (DrInC) SO ADDICTIVE BEHAVIORS LA English DT Article DE drinkers inventory of consequences; DrInC; psychometrics; SIP AB The Drinker Inventory of Consequences (DrInC) was developed for Project MATCH to assess the consequences of drinking in five domains. The present study, using baseline data from the 1382 participants involved in the COMBINE Study, analyzed the psychometrics of the 50-item DrInC and its shorter form, the 15-item SIP. Findings indicate the DrInC is reliable, valid, and clinically useful and that DrInC subscales are internally consistent and non-redundant. In an examination of the shorter version of the DrInC, findings suggest that the SIP is suitable when assessing the overall level of drinking-related consequences. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ New Mexico, CASAA, Albuquerque, NM 87106 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Univ Washington, Dept Psychol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Forcehimes, AA (reprint author), Univ New Mexico, CASAA, 2650 Yale Blvd SE, Albuquerque, NM 87106 USA. EM AForcehimes@comcast.net; jtonigan@unm.edu; wrmiller@unm.edu; George_Kenna@brown.edu; jsbaer@u.washington.edu NR 7 TC 33 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD AUG PY 2007 VL 32 IS 8 BP 1699 EP 1704 DI 10.1016/j.addbeh.2006.11.009 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 179PS UT WOS:000247302800014 PM 17182194 ER PT J AU Miller, RA Harrison, DE Astle, CM Floyd, RA Flurkey, K Hensley, KL Javors, MA Leeuwenburgh, C Nelson, JF Ongini, E Nadon, NL Warner, HR Strong, R AF Miller, Richard A. Harrison, David E. Astle, Clinton M. Floyd, Robert A. Flurkey, Kevin Hensley, Kenneth L. Javors, Martin A. Leeuwenburgh, Christiaan Nelson, James F. Ongini, Ennio Nadon, Nancy L. Warner, Huber R. Strong, Randy TI An aging Interventions Testing Program: study design and interim report SO AGING CELL LA English DT Article DE aging; aspirin; longevity; mice; nordihydroguiaretic acid ID GENETICALLY HETEROGENEOUS MICE; TERT-BUTYL NITRONE; NORDIHYDROGUAIARETIC ACID NDGA; QUANTITATIVE TRAIT LOCI; GROWTH-FACTOR-I; LIFE-SPAN; SPIN-TRAP; ACETYLSALICYLIC-ACID; CHOLINE-DEFICIENT; GENE-EXPRESSION AB The National Institute on Aging's Interventions Testing Program (ITP) has developed a plan to evaluate agents that are considered plausible candidates for delaying rates of aging. Key features include: (i) use of genetically heterogeneous mice (a standardized four-way cross), (ii) replication at three test sites (the Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT), (iii) sufficient statistical power to detect 10% changes in lifespan, (iv) tests for age-dependent changes in T cell subsets and physical activity, and (v) an annual solicitation for collaborators who wish to suggest new interventions for evaluation. Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-alpha-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). An interim analysis was conducted using survival data available on the date at which at least 50% of the male control mice had died at each test site. Survival of control males was significantly higher, at the interim time-point, at UM than at UT or TJL; all three sites had similar survival of control females. Males in the NDGA group had significantly improved survival (P = 0.0004), with significant effects noted at TJL (P < 0.01) and UT (P < 0.04). None of the other agents altered survival, although there was a suggestion (P = 0.07) of a beneficial effect of aspirin in males. More data will be needed to determine if any of these compounds can extend maximal lifespan, but the current data show that NDGA reduces early life mortality risks in genetically heterogeneous mice at multiple test sites. C1 Univ Michigan, Med Ctr, Geriatr Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Florida, Dept Aging & Geriatr, Gainesville, FL 32610 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, Dept Physiol, San Antonio, TX 78229 USA. Nicox Res Inst, Milan, Italy. NIA, Biol Aging Program, Bethesda, MD 20892 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Res Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, Dept Pharmacol, San Antonio, TX 78229 USA. RP Miller, RA (reprint author), Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. EM millerr@umich.edu FU NIA NIH HHS [AG022303, AG022307, AG022308, AG025707, AG13319] NR 59 TC 77 Z9 78 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2007 VL 6 IS 4 BP 565 EP 575 DI 10.1111/j.1474-9726.2007.00311.x PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 190VF UT WOS:000248088000017 PM 17578509 ER PT J AU Zhao, XQ Phan, BAP Chu, BC Bray, F Moore, AB Polissar, NL Dodge, JT Lee, CD Hatsukami, TS Yuan, C AF Zhao, Xue-Qiao Phan, Binh An P. Chu, Baocheng Bray, Frank Moore, Andrew B. Polissar, Nayak L. Dodge, J. Theodore, Jr. Lee, Colin D. Hatsukami, Thomas S. Yuan, Chun TI Testing the hypothesis of atherosclerotic plaque lipid depletion during lipid therapy by magnetic resonance imaging: Study design of Carotid Plaque Composition Study SO AMERICAN HEART JOURNAL LA English DT Article ID IN-VIVO; CORONARY ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; LOWERING THERAPY; REGRESSION DIETS; CHOLESTEROL; PROGRESSION; PREVENTION; NIACIN; TRIAL AB Background In vivo testing of the lipid depletion hypothesis in human beings during lipid-modifying therapy has not been possible until recent developments in magnetic resonance imaging (MRI). Trial Design The Carotid Plaque Composition Study is a prospective, randomized study designed to test the lipid depletion hypothesis in vivo. One hundred twenty-three subjects with coronary artery disease (CAD) or carotid disease and with levels of apolipoprotein B >= 120 mg/dL (low-density lipoprotein levels 100-190 mg/dL) were enrolled and randomized to (1) single therapy-atorvastatin alone, placebos for extended release (ER)-niacin and colesevelam; (2) double therapy-atorvastatin plus ER-niacin (2 g/d), and placebo for colesevelam; (3) triple therapy-atorvastatin, ERniacin, plus colesevelam (3.8 9/d). All subjects will undergo MRI scans of bilateral carotid arteries at baseline and annually for 3 years for a total of 4 examinations while on active therapy., Among these 123 subjects with mean age of 55 years and mean body mass index of 30 kg/m(2), 73% are male, 43% have a family history of premature cardiovascular disease, 37% have had a previous myocardial infarction, 80% have clinically established CAD, 52% are hypertensive, 12% have diabetes, 23% are current smokers, and 47% meet the criteria for metabolic syndrome. The baseline carotid disease is evaluated using a MRI-modified American Heart Association lesion type definition. Of the 123 enrolled subjects, 40% have type III lesions with small eccentric plaque, 52% have type IV to V lesions with a necrotic core, and only 4% have calcified plaque based on the most diseased carotid location. Conclusions The Carotid Plaque Composition Study uses a state-of-the-art imaging technology and comprehensive lipid management to test the plaque lipid depletion hypothesis in CAD subjects. C1 Univ Washington, Div Cardiol, Dept Med, Seattle, WA 98103 USA. Univ Washington, Dept Radiol, Vasc Imaging Lab, Seattle, WA USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. Yakima Heart Ctr, Yakima, WA USA. Idaho Cardiol Assoc, Boise, ID USA. Univ Washington, Div Vasc, Seattle, WA USA. VA Puget Sound Hlth Care, Seattle, WA USA. RP Zhao, XQ (reprint author), Univ Washington, Div Cardiol, Dept Med, Box 358771,1914 N 34th St,Suite 204, Seattle, WA 98103 USA. EM xueqiao@u.washington.edu FU NHLBI NIH HHS [R01 HL63895] NR 31 TC 28 Z9 28 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2007 VL 154 IS 2 BP 239 EP 246 DI 10.1016/j.ahj.2007.04.035 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 196VT UT WOS:000248511000009 PM 17643572 ER PT J AU Wang, TJ Larson, MG Benjamin, EJ Siwik, DA Safa, R Guo, CY Corey, D Sundstrom, J Sawyer, DB Colucci, WS Vasan, RS AF Wang, Thomas J. Larson, Martin G. Benjamin, Emelia J. Siwik, Deborah A. Safa, Radwan Guo, Chao-Yu Corey, Diane Sundstrom, Johan Sawyer, Douglas B. Colucci, Wilson S. Vasan, Ramachandran S. TI Clinical and echocardiographic correlates of plasma procollagen type III amino-terminal pepticle levels in the community SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; EXTRACELLULAR-MATRIX TURNOVER; LEFT-VENTRICULAR HYPERTROPHY; CARDIOVASCULAR RISK-FACTORS; SERUM CONCENTRATIONS; AMINOTERMINAL PROPEPTIDE; DILATED CARDIOMYOPATHY; ESSENTIAL-HYPERTENSION; NATRIURETIC-PEPTIDE; COLLAGEN-SYNTHESIS AB Background Left ventricular remodeling is characterized by increased collagen deposition in the extracellular matrix. Levels of plasma procollagen type III amino-terminal peptide (PIIINP), a marker of collagen turnover, are elevated in the setting of recent myocardial infarction, heart failure, and cardiornyopathy. Whether plasma PIIINP levels are a useful indicator of subclinical left ventricular abnormalities in ambulatory individuals has not been studied. Methods We examined 967 Framingham Heart Study participants (mean age, 56 years; 60% women) who underwent routine echocardiography and measurement of plasma PIIINP levels. All participants were free of prior myocardial infarction or heart failure. Multivariable regression analyses were performed to examine the clinical and echocardiographic correlates of PIIINP levels. Results Plasma PIIINP levels increased with age and body mass index but did not significantly correlate with other cardiovascular risk factors including hypertension and diabetes. In multivariable models, there was no association between plasma PIIINP levels and left ventricular mass (P =.89), left ventricular fractional shortening ( P =.15), left ventricular end-diastolic dimension (P =.5 1), or left atrial size (P =.68). Plasma PIIINP levels were positively correlated with tissue inhibitor of metalloproteinase-1 levels (multivariable-adjusted, P =.001). Conclusions The use of biomarkers of extracellular matrix turnover has generated recent interest, with plasma PIIINP being the most commonly studied biomarker in acute settings. However, our findings in a large, community-based cohort suggest that plasma PIIINP has limited use for the detection of structural heart disease in ambulatory individuals. C1 Harvard Univ, Massachusetts Gen Hosp, Med Sch, Cardiol Div, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Vanderbilt Univ, Ctr Med, Cardiol Div, Nashville, TN USA. Boston Univ, Sch Med, Boston Med Ctr, Sect Cardiol, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Med Ctr, Myocardial Biol Unit, Boston, MA USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Med Sch, Cardiol Div, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tiwang@partners.org RI Sundstrom, Johan/A-6286-2009 OI Sundstrom, Johan/0000-0003-2247-8454 FU NHLBI NIH HHS [HL080124, K23 HL074077, K23-HL074077, K24 HL004334, K23 HL074077-05, K24 HL004334-08, K24-HL-04334, N01 HC025195, N01-HC-25195, N01HC25195, R01 HL080124, R01 HL080124-04] NR 46 TC 18 Z9 19 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2007 VL 154 IS 2 BP 291 EP 297 DI 10.1016/j.ahj.2007.04.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 196VT UT WOS:000248511000015 PM 17643579 ER PT J AU Singla, I Zahid, M Good, CB Macioce, A Sonel, AF AF Singla, Ish Zahid, Maliha Good, Chester B. Macioce, Alanna Sonel, Ali F. TI Effect of hyponatremia (< 135 mEq/L) on outcome in patients with Non-ST-elevation acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; HEART-FAILURE; MORTALITY; TERM AB Hyponatremia is associated with adverse outcomes in patients with heart failure and ST-elevation myocardial infarction (STEMI). We evaluated the effect of hyponatremia on outcomes in patients with suspected acute coronary syndrome and non-STEMI. All patients had a sodium level determined at time of admission, at 24 and 48 hours, and at discharge. Of 1,478 patients, 341 (23.1%) were hyponatremic (sodium < 135 mEq/L) on presentation. Patients who had hyponatremia on admission were significantly more likely to die or have recurrent myocardial infarction in the next 30 days (odds ratio 1.98, 95% confidence interval 1.35 to 2.89, p < 0.001). This relation persisted after adjusting for factors such as age, left ventricular ejection fraction, use of diuretics before admission, hypotension on presentation, anemia, chronic renal insufficiency, pulmonary edema, and high troponin levels (odds ratio 1.7, 95% confidence interval 1.1 to 2.5, p = 0.01). In conclusion, hyponatremia on admission is associated with 30-day adverse outcome in patients presenting with suspected acute coronary syndrome/non-STEMI. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Hlth Equ & Res Promot, Pittsburgh, PA USA. RP Zahid, M (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM maz7@pitt.edu NR 11 TC 17 Z9 18 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2007 VL 100 IS 3 BP 406 EP 408 DI 10.1016/j.amjcard.2007.03.039 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 197TJ UT WOS:000248579100004 PM 17659918 ER PT J AU Rivera, JJ Nasir, K Campbell, C Carvalho, JAM Blumenthal, RS Santos, RD AF Rivera, Juan J. Nasir, Khurram Campbell, Catherine Carvalho, Jose A. M. Blumenthal, Roger S. Santos, Raul D. TI Relation of plasma lipoprotein levels with low-grade inflammation in white men without clinical evidence of myocardial ischemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD-CELL COUNT; ALL-CAUSE MORTALITY; HDL CHOLESTEROL; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; INDEPENDENT PREDICTOR; TRIGLYCERIDE LEVEL; LDL CHOLESTEROL; RISK-FACTORS AB There is a growing body of evidence indicating that high triglyceride levels ate an independent risk factor for cardiovascular disease (CVD) events. In this study we compared the association of fasting levels of non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and triglycerides with white blood cell (WBC) count, An inflammatory marker associated with an adverse CVD prognosis. We studied 458 asymptornatic men (46.0 +/- 7.0 years old) who presented for CVD, risk stratification. WBC count (x 10(9) cells/L) increased significantly across increasing tertiles of triglyceride level (tertile 1, 6.04 +/- 1.49; tertile 2 6.21 +/- 1.44; tertile 3 6.78 +/- 1.73, p < 0.0001), whereas a trend of lower WBC counts was observed across increasing tertiles of HDL cholesterol (tertile 1, 6.52 +/- 1.62; tertile 2, 6.24 +/- 1.50; tertile 3, 6.21 +/- 1.61, p = 0.08). In models adjusted for age, gender, and CVD risk factor, the odds ratio for a high WBC count (quartile >= 4 vs lower 3 quartiles) was significantly higher with increasing levels of triglyceride (2.4, 95% confidence interval 1.3 to 4.8, p = 0.02). When all lipid variables were introduced in the models in addition to traditional CVD risk factors, the association between plasma triglyceride level and WBC count persisted (p = 0.04), which was not found for other lipid parameters. In conclusion, in our study, only plasma triglyceride level was independently associated with a higher WBC count. (c) 2007 Elsevier Inc. All rights reserved. C1 John Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. Massachusetts Gen Hosp, Harvard Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. Univ Sao Paulo, Med Sch Hosp, Lipid Clin Heart Inst, Sao Paulo, Brazil. RP Santos, RD (reprint author), John Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. EM rdsf@uol.com.br RI Santos, Raul/A-1170-2010 OI Santos, Raul/0000-0002-9860-6582 NR 25 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2007 VL 100 IS 3 BP 450 EP 454 DI 10.1016/j.amjcard.2007.03.044 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 197TJ UT WOS:000248579100013 PM 17659927 ER PT J AU Scranton, RE Lawler, E Botteman, M Chittamooru, S Gagnon, D Lew, R Harnett, J Gaziano, JM AF Scranton, Richard E. Lawler, Elizabeth Botteman, Marc Chittamooru, Subha Gagnon, David Lew, Robert Harnett, James Gaziano, J. Michael TI Effect of treating erectile dysfunction on management of systolic hypertension SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK-FACTORS; PREVALENCE; THERAPY; DISEASE AB Erectile dysfunction (ED) is a prevalent condition and a predictor of future cardiovascular events. Screening and treatment of ED may improve management of cardiovascular risk factors. We evaluated the potential beneficial effect of newly treating ED on the management of hypertension in men in the New England Veteran Affairs Healthcare System. We conducted a retrospective cohort study using medical record data to identify patients diagnosed with and treated at any time for hypertension who received a prescription for a phosphodiesterase type 5 inhibitor (PDE5i) before February 1, 2003. Fifty percent of 6,768 men (mean +/- SD 61.6 +/- 9.9 years of age) had a systolic blood pressure (BP) >= 140 mm. Hg before PDE5i administration. Overall, there was a decrease in systolic BP by 1.43 mm Hg (95% confidence interval - 1.69 to - 1.18) after initiation of PDE5i. The decrease in systolic BP was most pronounced in men with a systolic BP 160 mm Hg at baseline (- 17.8 mm Hg, 95% confidence interval -18.8 to -16.8). After initiating therapy with PDE5i, patients were more likely to start an antihypertensive medication (17.3%) versus stop therapy (2.3%) and add additional antihypertensive medication to their existing therapy (42.2%) versus decrease the number of medications (17.3%). Surveillance also increased with total number of systolic BP measurements increasing by 42%. In conclusion, men with high systolic BP who initiated ED therapy had improvements in systolic BP control that may be related to clinically relevant behaviors, such as more aggressive monitoring and treatment with antihypertensive medications. (c) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Pharmerit N Amer, LLC, Bethesda, MD USA. Pfizer Inc, New York, NY USA. RP Scranton, RE (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. EM richardscrantonmd@rcn.com OI Gagnon, David/0000-0002-6367-3179 NR 9 TC 14 Z9 14 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2007 VL 100 IS 3 BP 459 EP 463 DI 10.1016/j.amjcard.2007.03.045 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 197TJ UT WOS:000248579100015 PM 17659929 ER PT J AU Varraso, R Fung, TT Barr, RG Hu, FB Willett, W Camargo, CA AF Varraso, Raphaelle Fung, Teresa T. Barr, R. Graham Hu, Frank B. Willett, Walter Camargo, Carlos A., Jr. TI Prospective study of dietary patterns and chronic obstructive pulmonary disease among US women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary pattern; principal component analysis; chronic obstructive pulmonary disease; COPD; prospective cohort; body mass index ID BODY-MASS INDEX; FRESH FRUIT CONSUMPTION; LUNG-FUNCTION; GENERAL-POPULATION; RISK; MORTALITY; HEALTH; QUESTIONNAIRE; NUTRITION; CHILDREN AB Background: Although many foods and nutrients are associated with lung function or symptoms of chronic obstructive pulmonary disease (COPD), the relation between overall diet and newly diagnosed COPD is not known. Objective: We assessed the relation between dietary patterns and newly diagnosed COPD in women. Design: Data were collected from a large prospective cohort of US women (Nurses' Health Study). Between 1984 and 2000, 754 self-reported confirmed cases of newly diagnosed COPD were identified among 72 043 women. With the use of principal component analysis, 2 dietary patterns were identified: a prudent pattern (fruit, vegetables, fish, whole-grain products) and a Western pattern (refined grains, cured and red meats, desserts, French fries). Patterns were categorized into quintiles, and the risk of COPD was compared between quintiles (lowest as reference) with the use of Cox proportional hazard models. Results: After adjustments for 14 potential confounders, the prudent pattern was negatively associated with risk of newly diagnosed COPD [relative risk (RR) for highest compared with lowest quintile: 0.75; 95% CI: 0.58, 0.98; P for trend = 0.02] whereas the Western pattern was positively associated with risk of COPD (RR for highest compared with lowest quintile: 1.31; 95% CI: 0.94, 1.82; P for trend = 0.02). In contrast with findings for COPD, dietary patterns were not associated with the risk of adult-onset asthma. Conclusion: In women, a negative association was found between a diet rich in fruit, vegetables, and fish and the risk of COPD, whereas a positive association was found between a diet rich in refined grains, cured and red meats, desserts, and French fries and the risk of COPD. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Simmons Coll, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Columbia Univ, Med Ctr, Dept Med, Dept Epidemiol,Div Gen Med, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Varraso, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM rvarraso@hsph.harvard.edu RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 FU NCI NIH HHS [CA-87969, P01 CA087969]; NHLBI NIH HHS [R01 HL075476, HL-075476, HL-077612, HL-60712, HL-63841, R01 HL060712, R01 HL075476-01, R01 HL077612, R01 HL077612-04]; NIAID NIH HHS [AI-52338, R21 AI052338]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 45 TC 62 Z9 66 U1 2 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2007 VL 86 IS 2 BP 488 EP 495 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 198LN UT WOS:000248629700030 PM 17684223 ER PT J AU Troy, LM Jacques, PF Hannan, MT Kiel, DP Lichtenstein, AH Kennedy, ET Booth, SL AF Troy, Lisa M. Jacques, Paul F. Hannan, Marian T. Kiel, Douglas P. Lichtenstein, Alice H. Kennedy, Eileen T. Booth, Sarah L. TI Dihydrophylloquinone intake is associated with low bone mineral density in men and women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dihydrophylloquinone; vitamin K; partially hydrogenated fat; trans fatty acids; diet patterns; bone mineral density; osteoporosis ID FOOD FREQUENCY QUESTIONNAIRE; VITAMIN-K; FRAMINGHAM OSTEOPOROSIS; RISK-FACTORS; FATTY-ACIDS; ELDERLY-MEN; HEALTH; PHYLLOQUINONE; VALIDITY; OILS AB Background: Poor diet may affect bone status by displacing nutrients involved in bone health. Dihydrophylloquinone, a form of vitamin K present in foods made with partially hydrogenated fat, is a potential marker of a low-quality dietary pattern. Objective: Our objective was to examine the cross-sectional associations between dihydrophylloquinone intake and bone mineral density (BMD) of the hip and spine in men and women. Design: Dihydrophylloquinone intake was estimated with a food-frequency questionnaire, and BMD (in g/cm(2)) was measured by dual-energy X-ray absorptiometry in 2544 men and women (mean age: 58.5 y) who had participated in the Framingham Offspring Study. General linear models were used to examine the associations between dihydrophylloquinone intake (in tertiles: < 15.5, 15.5-29.5, and > 29.5 mu g/d) and hip and spine BMD after adjustment for age, body mass index, energy intake, calcium intake, vitamin D intake, smoking status, physical activity score, and, for women, menopause status and estrogen use. Results: Higher dihydrophylloquinone intakes were associated with lower mean BMD at the femoral neck [lowest-to-highest tertiles (95% CI): 0.934 (0.925, 0.942), 0.927 (0.919, 0.935), and 0.917 (0.908, 0.926), P for trend = 0.02], the trochanter [lowest-to-highest tertiles (95% CI): 0.811 (0.802, 0.820), 0.805 (0.797, 0.813), and 0.795 (0.786, 0.804), P for trend = 0.02], and the spine [lowest-to-highest tertiles (95% CI): 1.250 (1.236, 1.264), 1.243 (1.242, 1.229), and 1.227 (1.213, 1.242), P for trend = 0.03] in men and women after adjustment for the covariates. Further adjustment for markers of healthy and low-quality dietary patterns did not affect the observed associations. Conclusions: Higher dihydrophylloquinone intakes are associated with lower BMD in men and women. This association remains significant after adjustment for other markers of diet quality. C1 Tufts Univ, USDA, Human Nutr Res Ctr, Boston, MA 02111 USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA USA. Inst Aging Res, Boston, MA USA. Harvard Univ, Sch Med, Div Gerontol, BIDMC, Boston, MA USA. RP Booth, SL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr, 711 Washington St, Boston, MA 02111 USA. EM sarah.booth@tufts.edu OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-25195]; NIA NIH HHS [AG14759, AR/AG 41398] NR 25 TC 9 Z9 9 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2007 VL 86 IS 2 BP 504 EP 508 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 198LN UT WOS:000248629700032 PM 17684225 ER PT J AU Melanson, SEF Morrow, DA Jarolim, P AF Melanson, Stacy E. F. Morrow, David A. Jarolim, Petr TI Earlier detection of myocardial injury in a preliminary evaluation using a new troponin I assay with improved sensitivity SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE acute coronary syndrome; myocardial injury; troponin; early detection; sensitive assay; early presenters ID ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; CARDIAC TROPONIN; BIOCHEMICAL MARKERS; RISK STRATIFICATION; AMERICAN-COLLEGE; EUROPEAN-SOCIETY; UNSTABLE ANGINA; CHEST-PAIN; INFARCTION AB Cardiac troponins are important biochemical markers for defining the presence of myocardial injury. However, limitations in troponin testing exist, including the relatively late increase in troponin after onset of ischemia. We therefore evaluated a more sensitive troponin assay for detection of myocardial injury in "early presenters." Discarded serial specimens were obtained from 103 patients who had a negative cardiac troponin I (cTnI) result followed by a positive cTnI result. Results were obtained using our current cTnI method and a new more sensitive assay, TnI- Ultra (Siemens Medical Solutions, Diagnostics Division, Tarrytown, NY). Medical records were reviewed to determine the clinical diagnosis. Precision studies yielded a 10% coefficient of variation at the diagnostic cut points for cTnI (0. 10 ng/mL [0. 10 mu g/L]) and TnI-Ultra (0. 04 ng/mL [0. 04 mu g/L]). TnI- Ultra was positive before cTnI in 66 (64. 1 %) of 103 cases. We conclude that the more sensitive assay, TnI- Ultra, has better analytic performance and has the potential to detect myocardial injury earlier than the current cTnI assay. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Clin Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Jarolim, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Clin Labs, 75 Francis St,Amory 2, Boston, MA 02115 USA. NR 29 TC 134 Z9 140 U1 1 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2007 VL 128 IS 2 BP 282 EP 286 DI 10.1309/Q9W5HJTT24GQCXXX PG 5 WC Pathology SC Pathology GA 191UV UT WOS:000248158400012 PM 17638663 ER PT J AU Caudle, DD Senior, AC Wetherell, JL Rhoades, HM Beck, JG Kunik, ME Snow, AL Wilson, NL Stanley, MA AF Caudle, Donald D. Senior, Ashley C. Wetherell, Julie Loebach Rhoades, Howard M. Beck, J. G. Kunik, Mark E. Snow, A. Lynn Wilson, Nancy L. Stanley, Melinda A. TI Cognitive errors, symptom severity, and response to cognitive behavior therapy in older adults with generalized anxiety disorder SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE generalized anxiety disorder; cognitive behavior therapy; older adults; Mini-Mental Status Examination ID EXECUTIVE DYSFUNCTION; GERIATRIC DEPRESSION; REALITY ORIENTATION; LIFE; PROGRESSION; VALIDATION; DISABILITY; AMSTERDAM; DISEASE; SCALE AB Objective: Recent research by Wetherell et al. investigating the differential response to group-administered cognitive behavior therapy ( CBT) for generalized anxiety disorder ( GAD) in older adults found that GAD severity, homework adherence, and psychiatric comorbidity predicted statistically significant improvement. The current study investigated whether the presence/absence of cognitive errors on separate domains of the Mini-Mental State Exam ( MMSE) predicted baseline differences in symptom severity and improvement following CBT, above and beyond already established predictors. Methods: Baseline characteristics were investigated in a sample of 208 older patients diagnosed with GAD. Predictors of treatment response were examined in a sub-sample of 65 patients who completed CBT and were included in a prior study by Wetherell et al. of response predictors. Results: Results from the baseline sample indicated that only subjects who committed an error on the MMSE Working Memory domain exhibited increased severity in anxiety and depressive symptoms. Results from the treatment sample indicated that an error on the MMSE Orientation domain was a significant predictor of outcome at 6-month follow-up, while controlling for previously established predictors. Patients who committed at least one error in this domain showed decreased response relative to patients who committed no errors. Conclusion: In this sample of older adults diagnosed with GAD, poor performance on the MMSE Working Memory domain was associated with increased baseline anxiety and depression, while baseline performance differences on the MMSE Orientation domain predicted outcome six months after CBT intervention. C1 Univ Houston, Dept Educ Psychol, Houston, TX USA. Univ Houston, Dept Psychol, Houston, TX USA. Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies MEDVAMC, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Vet Affairs San Diego Hlth Care Syst, Psychol Serv, San Diego, CA USA. SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. Univ Alabama, Dept Psychol, Ctr Mental Hlth & Aging, Tuscaloosa, AL 35487 USA. RP Stanley, MA (reprint author), Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies MEDVAMC, Dept Psychiat & Behav Sci, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mstanley@bcm.tmc.edu NR 60 TC 28 Z9 28 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD AUG PY 2007 VL 15 IS 8 BP 680 EP 689 DI 10.1097/JGP.0b013e31803c550d PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 196MW UT WOS:000248487700006 PM 17670997 ER PT J AU Moran, A Simon, JA Shiboski, S Pickering, TG Waters, D Rotter, JI Lyon, C Nickerson, D Yang, H Saad, M Hsueh, W Krauss, RM AF Moran, Andrew Simon, Joel A. Shiboski, Stephen Pickering, Thomas G. Waters, David Rotter, Jerome I. Lyon, Christopher Nickerson, Deborah Yang, Huiying Saad, Mohammed Hsueh, Willa Krauss, Ronald M. TI Differential effects of Ramipril on ambulatory blood pressure in African Americans and Caucasians SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE ambulatory blood pressure; nondipping; pharmacotherapy; angiotensin-converting enzyme inhibitors; African American; Caucasian ID CONVERTING-ENZYME-INHIBITION; WHITE HYPERTENSIVE PATIENTS; ANTIHYPERTENSIVE RESPONSE; ETHNIC-DIFFERENCES; MANAGEMENT; BLACKS; THERAPY; PROFILE; RACE; MECHANISMS AB Background: On average, angiotensin-converting enzyme inhibitors produce less office blood-pressure lowering in African Americans compared with Caucasians. Past studies did not compare daytime and nighttime ambulatory blood-pressure responses to angiotensin-converting enzyme inhibitors in African Americans and Caucasians. Methods: We measured the office and ambulatory bloodpressure response to 8 weeks of a fixed dose of 10 mg daily of the angiotensin-converting enzyme inhibitor ramipril in a cohort of 72 African Americans and 89 Caucasians. Results: Ramipril lowered age-adjusted daytime ambulatory systolic blood pressure 6 mm Hg and diastolic blood pressure 3 mm Hg less in African Americans compared with Caucasians (both P =.02). This difference persisted after adjusting for baseline blood pressure, body mass index, urine sodium and potassium, plasma aldosterone, and other covariates. Despite the difference in mean response, there was a 72% overlap in daytime blood-pressure response to ramipril between African Americans and Caucasians. Among Caucasians, ramipril lowered systolic blood pressure 2 mm Hg less during nighttime compared with daytime, whereas among African Americans, blood pressure lowering was equivalent during day and night. Nighttime blood-pressure response to ramipril did not differ significantly between African Americans and Caucasians. Conclusions: Ramipril was more effective in lowering daytime blood pressure in Caucasians compared with African Americans, but appreciable differences in response did not persist at night. Despite the small difference in mean response between groups, the majority of African Americans and Caucasians had a similar blood-pressure response to a fixed dose of ramipril. C1 Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Columbia Univ, Dept Med, Sch Med, New York, NY USA. Columbia Univ, Behav Cardiovasc Hlth & Hypertens Program, Sch Med, New York, NY USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Sch Med, San Francisco, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Washington, Dept Genome Sci, Seattle, WA USA. SUNY Hlth Sci Ctr, Dept Prevent Med, Stony Brook, NY USA. RP Krauss, RM (reprint author), Childrens Hosp, Oakland Res Inst, 5700 Martin Luther King, Oakland, CA 94609 USA. EM rkrauss@chori.org FU NHLBI NIH HHS [U01 HL69757] NR 30 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 2007 VL 20 IS 8 BP 884 EP 891 DI 10.1016/j.amjhyper.2007.02.006 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 201ZR UT WOS:000248871700013 PM 17679038 ER PT J AU Plomondon, ME Magid, DJ Steiner, JF MaWhinney, S Gifford, BD Shih, SC Grunwald, GK Rumsfeld, JS AF Plomondon, Mary E. Magid, David J. Steiner, John F. MaWhinney, Samantha Gifford, Blair D. Shih, Sarah C. Grunwald, Gary K. Rumsfeld, John S. TI Primary care provider turnover and quality in managed care organizations SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PATIENT SATISFACTION; PHYSICIAN TURNOVER; INTERPERSONAL CONTINUITY; HEALTH-CARE; BREAST; CANCER; SERVICES; DELIVERY; COSTS; ASSOCIATION AB Objectives:To examine the association between primary care provider turnover in managed care organizations and measures of member satisfaction and preventive care. Study Design: Retrospective cohort study of a national sample of 615 managed care organizations that reported HEDIS (R) data to the National Committee for Quality Assurance from 1999 through 2001. Methods: Multivariable hierarchical regression modeling was used to evaluate the association between health plan primary care provider turnover rate and member satisfaction and preventive care measures, including childhood immunization, well-child visits, cholesterol, diabetes management, and breast and cervical cancer screening, adjusting for patient and organizational characteristics, time, and repeated measures. Results:The median primary care provider turnover rate was 7.1% (range, 0%-53.3%). After adjustment for plan characteristics, health plans with higher primary care provider turnover rates had significantly lower measures of member satisfaction, including overall rating of healthcare (P < .01). A 10% higher primary care provider turnover rate was associated with 0.9% fewer members rating high overall satisfaction With healthcare. Health plans with higher provider turnover rates also had lower rates of preventive care, including childhood immunization (P = .045), well-child visits (P = .002), cholesterol screening after cardiac event (P = .042), and cervical cancer screening (P = .024). For example, a 10% higher primary care provider turnover was associated with a 2.7% lower rate of child-members receiving well-child visits in the first 15 months of life. Conclusions: Primary care provider turnover is associated with several measures of care quality, including aspects of member satisfaction and preventive care. Future studies should evaluate whether interventions to reduce primary care provider turnover can improve quality of care and patient outcomes. C1 Denver VAMC, Eastern Colorado Hlth Care Syst, Care Coordinat Res Program, Dept Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Colorado Permanente Med Grp, Denver, CO USA. NCQA, Washington, DC USA. RP Plomondon, ME (reprint author), Denver VAMC, Eastern Colorado Hlth Care Syst, Care Coordinat Res Program, Dept Vet Affairs Med Ctr, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM meg.plomondon@va.gov NR 54 TC 21 Z9 22 U1 1 U2 3 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2007 VL 13 IS 8 BP 465 EP 472 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 202VG UT WOS:000248931500003 PM 17685827 ER PT J AU Hill, AD Chang, BS Hill, RS Garraway, LA Bodell, A Sellers, WR Walsh, CA AF Hill, Anthony D. Chang, Bernard S. Hill, R. Sean Garraway, Levi A. Bodell, Adria Sellers, William R. Walsh, Christopher A. TI A 2-mb critical region implicated in the microcephaly associated with terminal 1q deletion syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE terminal 1q deletion syndrome; microcephaly and hypoplasia of the corpus callosum; deletion 1q43-1q44 ID DANDY-WALKER MALFORMATION; PARTIAL TRISOMY 9P; DISTAL LONG ARM; MENTAL-RETARDATION; ORGAN GROWTH; BRAIN SIZE; CHROMOSOME-1; PHENOTYPE; ANOMALIES; MECHANISM AB Patients with distal deletions of chromosome 1q have a recognizable syndrome that includes rnicrocephaly, hypoplasia or agenesis of the corpus callosum, and psychomotor retardation. Although these symptoms have been attributed to deletions of 1q42-1q44, the minimal chromosomal region involved has not been identified. Using microsatellite and single nucleotide polymorphism (SNP) markers, we have mapped the deleted regions in seven patients with terminal deletions of chromosome 1q to define a 2.0 Mb microcephaly critical region including the 1q43-1q44 boundary and no more than 11 genes. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Howard Hughes Med Inst, Dept Neurol, Sch Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Walsh, CA (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Neurol, Sch Med,Beth Israel Deaconess Med Ctr, New Res Bldg Room 266,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwalsh@bidmc.harvard.edu FU NINDS NIH HHS [R37 NS035129, T32 NS07484] NR 24 TC 36 Z9 37 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG 1 PY 2007 VL 143A IS 15 BP 1692 EP 1698 DI 10.1002/ajmg.a.31776 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 205WI UT WOS:000249144900003 PM 17603806 ER PT J AU Fang, MC Go, AS Chang, YC Hylek, EM Henault, LE Jensvold, NG Singer, DE AF Fang, Margaret C. Go, Alan S. Chang, Yuchiao Hylek, Elaine M. Henault, Lori E. Jensvold, Nancy G. Singer, Daniel E. TI Death and disability from warfarin-associated intracranial and extracranial hemorrhages SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE atrial fibrillation; death; disability; hemorrhage; intracranial hemorrhage; warfarin ID ORAL ANTICOAGULANT-THERAPY; ATRIAL-FIBRILLATION; ANTITHROMBOTIC THERAPY; RISK-FACTORS; INTRACEREBRAL HEMORRHAGE; PREDICTING STROKE; INTENSITY; MORTALITY; TRIALS; AGE AB OBJECTIVES: Little is known about the outcomes of patients who have hemorrhagic complications while receiving warfarin therapy. We examined the rates of death and disability resulting from warfarin-associated intracranial and extracranial hemorrhages in a large cohort of patients with atrial fibrillation. METHODS: We assembled a cohort of 13,559 adults with nonvalvular atrial fibrillation and identified patients hospitalized for warfarin-associated intracranial and major extracranial hemorrhage. Data on functional disability at discharge and 30-day mortality were obtained from a review of medical charts and state death certificates. The relative odds of 30-day mortality by hemorrhage type were calculated using multivariable logistic regression. RESULTS: We identified 72 intracranial and 98 major extracranial hemorrhages occurring in more than 15,300 person-years of warfarin exposure. At hospital discharge, 76% of patients with intracranial hemorrhage had severe disability or died, compared with only 3% of those with major extracranial hemorrhage. Of the 40 deaths from warfarin-associated hemorrhage that occurred within 30 days, 35 (88%) were from intracranial hemorrhage. Compared with extracranial hemorrhages, intracranial events were strongly associated with 30-day mortality (odds ratio 20.8 [95% confidence interval, 6.0-72]) even after adjusting for age, sex, anticoagulation intensity on admission, and other coexisting illnesses. CONCLUSIONS: Among anticoagulated patients with atrial fibrillation, intracranial hemorrhages caused approximately 90% of the deaths from warfarin-associated hemorrhage and the majority of disability among survivors. When considering anticoagulation, patients and clinicians need to weigh the risk of intracranial hemorrhage far more than the risk of all major hemorrhages. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Gen Internal Med & Clin Epidemiol Unit, Boston, MA 02118 USA. RP Fang, MC (reprint author), Univ Calif San Francisco, Dept Med, Hosp Grp, 533 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU NIA NIH HHS [AG15478, K23 AG028978, R01 AG015478] NR 30 TC 233 Z9 238 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2007 VL 120 IS 8 BP 700 EP 705 DI 10.1016/j.amjmed.2006.07.034 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 199KM UT WOS:000248694700024 PM 17679129 ER PT J AU Akpek, EK Harissi-Dagher, M Petrarca, R Butrus, SI Pineda, R Aquavella, JV Dohlman, CH AF Akpek, Esen Karamursel Harissi-Dagher, Mona Petrarca, Robert Butrus, Salim I. Pineda, Roberto, II Aquavella, James V. Dohlman, Claes H. TI Outcomes of Boston keratoprosthesis in aniridia: A retrospective multicenter study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PENETRATING KERATOPLASTY; KERATOLIMBAL ALLOGRAFT; KERATOPATHY AB PURPOSE: To evaluate the long-term outcomes of keratopros thesis as an alternative surgical procedure in the management of aniridic keratopathy. DESIGN: Retrospective, multicenter case series. METHODS: Fifteen adult patients (16 eyes) with aniridia who were deemed at high risk for regular donor corneal transplantation underwent a Boston type I keratoprosthesis procedure for visual rehabilitation. Device retention rate, preoperative and postoperative visual acu ity, and intraoperative and postoperative complications were studied. RESULTS: The mean age of the patients was 45 (median 50) years. Six of the patients were females. Eleven patients had previously undergone donor corneal trans. plantations (average two grafts), with failure. In 10 patients, the keratoprosthesis surgery was combined with other procedures such as cataract extraction, tube shunt implantation, vitrectomy, and intraocular lens removal. No intraoperative complications were encountered. The follow-up ranged from two months to 85 months, with a median of 17 months. All devices remained in situ throughout the entire follow-up period. The visual acuity improved in all but one patient from a median of counting fingers (light perception to 20/300) to 20/200 (hand motions to 20/60). Comorbid preoperative conditions particularly optic nerve and foveal hypoplasia limited the final postoperative vision. No endophthalmitis or extrusion of the device occurred. One device required repair procedure without necessitating a removal. CONCLUSIONS: Keratoprosthesis offers significant vision benefits in this patient group. C1 Johns Hopkins Univ, Wilmer Inst, Sch Med, Ocular Surface & Dry Eye Clin, Baltimore, MD 21287 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. George Washington Univ, Washington, DC USA. Georgetown Univ, Washington, DC USA. Univ Rochester, Inst Eye, Rochester, NY 14627 USA. RP Akpek, EK (reprint author), Johns Hopkins Univ, Wilmer Inst, Sch Med, Ocular Surface & Dry Eye Clin, 600 N Wolfe St,Maumenee Bldg 317, Baltimore, MD 21287 USA. EM esakpek@jhmi.edu OI Petrarca, Robert/0000-0001-8693-3423 NR 13 TC 48 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2007 VL 144 IS 2 BP 227 EP 231 DI 10.1016/j.ajo.2007.04.036 PG 5 WC Ophthalmology SC Ophthalmology GA 196ZI UT WOS:000248521800009 PM 17543875 ER PT J AU Dennison, AC Noorigian, JV Robinson, KM Fisman, DN Cianci, HJ Moberg, P Bunting-Perry, L Martine, R Duda, J Stern, MB AF Dennison, Andrew C. Noorigian, Joseph V. Robinson, Keith M. Fisman, David N. Cianci, Heather J. Moberg, Paul Bunting-Perry, Lisette Martine, Rebecca Duda, John Stern, Matthew B. TI Failing in Parkinson disease - Identifying and prioritizing risk factors in recurrent fallers SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Parkinson disease; falling; risk factors; movement disorders; aging; neurodegenerative diseases ID POSTURAL CONTROL; ELDERLY PERSONS; COMMUNITY; PREVENTION; PREDICTION; ETIOLOGY; VALIDITY; PEOPLE; TRIAL; TASK AB Objectives: To identify falling risk factors in a study population of recurrent fallers compared with nonfallers who have Parkinson disease, and to prioritize falling risk factors in this patient population to target them for modification. Design: Twenty-three recurrent fallers and 25 nonfallers who have Parkinson disease were recruited, and they participated in a comprehensive assessment probing for the presence of falling risk factors. To identify falling risk factors, a group comparative design was used to compare recurrent fallers and nonfallers across an array of variables. To prioritize modeling using recursive partitioning was performed, those risk factors, entering into the model falling, risk factors identified in this and other studies that were considered potentially modifiable. Results: A specific profile of variables distinguished recurrent fallers who have Parkinson disease in our study population: higher disease severity, higher level of motor impairment, higher level of disability, impaired leg agility or lower-limb coordination, impaired ability to arise from a chair or compromised proximal lower-limb motor control, impaired ambulation, impaired motor planning of the hands and feet, impaired dynamic balance as measured by ability to walk in tandem, and fear of falling. Recursive partitioning prioritized three risk factors: impaired ambulation, impaired lower-limb motor planning, and orthostasis. Conclusions: In this study, an idiosyncratic failing risk factor profile was demonstrated among our subjects who have Parkinson disease. Three variables were prioritized for potential modification: impaired ambulation, impaired lower-limb motor planning, and orthostasis. C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Texas, Baylor Coll Med, Houston Med Sch Phys Med & Rehabilitat Alliance, Houston, TX USA. Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Dept Rehabil Med, Philadelphia, PA USA. Res Inst Hosp Sick Children, Child Hlth Evaluat Sci, Publ Hlth Lab Branch, Toronto, ON, Canada. Univ Penn HLth Syst, Penn Hosp, Dan Aaron Parkinsons Dis Rehabilitat Ctr, Philadelphia, PA USA. Univ Penn, Med Ctr, Dept Psychiat, Philadelphia, PA USA. Univ Penn Hlth Syst, Inst Neurol, Dept Neurol, Philadelphia, PA USA. RP Robinson, KM (reprint author), Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 41 TC 30 Z9 31 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2007 VL 86 IS 8 BP 621 EP 632 DI 10.1097/PHM.0b013e318115f41b PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 194ZX UT WOS:000248383400004 PM 17667192 ER PT J AU Frank, JA Erle, DJ AF Frank, James A. Erle, David J. TI Progress toward a systems biology approach to acute lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; STRESS C1 Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94121 USA. Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94121 USA. RP Frank, JA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco VA Med Ctr, 4150 Clement St Box 111D, San Francisco, CA 94121 USA. EM James.frank@ucsf.edu OI Erle, David/0000-0002-2171-0648 FU NHLBI NIH HHS [HL-69900, R01 HL088440, R56 HL088440] NR 13 TC 4 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2007 VL 293 IS 2 BP L290 EP L291 DI 10.1152/ajplung.00220.2007 PG 2 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 196CL UT WOS:000248459200005 PM 17575007 ER PT J AU Feliers, D Lee, MJ Ghosh-Choudhury, G Bomsztyk, K Kasinath, BS AF Feliers, Denis Lee, Myung-Ja Ghosh-Choudhury, Goutam Bomsztyk, Karol Kasinath, B. S. TI Heterogeneous nuclear ribonucleoprotein K contributes to angiotensin II stimulation of vascular endothelial growth factor mRNA translation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ANG II; VEGF; signal transduction; RNA-binding protein ID RENAL EPITHELIAL-CELLS; KINASE-C-DELTA; HNRNP-K; DIABETIC-NEPHROPATHY; INITIATION-FACTOR; TYROSINE-PHOSPHORYLATION; PROTEIN-SYNTHESIS; IN-VITRO; BINDING; ACTIVATION AB ANG II rapidly increases VEGF synthesis in proximal tubular epithelial cells through mRNA translation. The role of heterogeneous nuclear ribonucleoprotein K ( hnRNP K) in ANG II regulation of VEGF mRNA translation initiation was examined. ANG II activated hnRNP K as judged by binding to poly( C)- and poly( U)- agarose. ANG II increased hnRNP K binding to VEGF mRNA at the same time as it stimulated its translation, suggesting that hnRNP K contributes to VEGF mRNA translation. Inhibition of hnRNP K expression by RNA interference significantly reduced ANG II stimulation of VEGF synthesis. ANG II increased hnRNP K phosphorylation on both tyrosine and serine residues with distinct time courses; only Ser302 phosphorylation paralleled binding to VEGF mRNA. Src inhibition using PP2 or RNA interference inhibited PKC delta activity and prevented hnRNP K phosphorylation on both tyrosine and serine residues and its binding to VEGF mRNA. Under these conditions, ANG II- induced VEGF synthesis was inhibited. ANG II treatment induced redistribution of both VEGF mRNA and hnRNP K protein from light to heavy polysomal fractions, suggesting increased binding of hnRNP K to VEGF mRNA that is targeted for increased translation. This study shows that hnRNP K augments efficiency of VEGF mRNA translation stimulated by ANG II. C1 Univ Texas, Hlth Sci Ctr San Antonio, Dept Med Nephrol, O Brien Kidney Res Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Washington, Med Lake Union, Seattle, WA 98195 USA. RP Feliers, D (reprint author), Univ Texas, Hlth Sci Ctr San Antonio, Dept Med Nephrol, O Brien Kidney Res Ctr, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78285 USA. EM feliers@uthscsa.edu FU NIDDK NIH HHS [R01 DK-55815, DK-50190]; NIGMS NIH HHS [GM-45134]; PHS HHS [R01-KD-45978] NR 38 TC 21 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2007 VL 293 IS 2 BP F607 EP F615 DI 10.1152/ajprenal.00497.2006 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 196CJ UT WOS:000248459000022 PM 17581920 ER PT J AU Lenderink, AM Liegel, K Ljubanovic, D Coleman, KE Gilkeson, GS Holers, VM Thurman, JM AF Lenderink, Amanda M. Liegel, Katharine Ljubanovic, Danica Coleman, Kathrin E. Gilkeson, Gary S. Holers, V. Michael Thurman, Joshua M. TI The alternative pathway of complement is activated in the glomeruli and tubulointerstitium of mice with adriamycin nephropathy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proteinuria ID TUBULAR EPITHELIAL-CELLS; INHIBITORY MONOCLONAL-ANTIBODY; MEMBRANE ATTACK COMPLEX; RENAL-DISEASE; FACTOR-B; PROXIMAL TUBULES; INTERSTITIAL DISEASE; CHRONIC PROGRESSION; BRUSH-BORDER; MRL/LPR MICE AB The complement system effectively identifies and clears invasive pathogens as well as injured host cells. Uncontrolled complement activation can also contribute to tissue injury, however, and inhibition of this system may ameliorate many types of inflammatory injury. Several studies have demonstrated that the filtration of complement proteins into the renal tubules, as occurs during proteinuric renal disease, causes tubular inflammation and injury. In the present study, we tested the hypothesis that activation of the complement system in the urinary space requires an intact alternative pathway. Using a model of adriamycin- induced renal injury, which induces injury resembling focal segmental glomerulosclerosis, we examined whether mice deficient in factor B would be protected from the development of progressive tubulointerstitial injury. Complement activation was attenuated in the glomeruli and tubulointerstitium of mice with congenital deficiency of factor B ( fB(-/-)) compared with wild- type controls, demonstrating that complement activation does occur through the alternative pathway. Deficiency in factor B did not significantly protect the mice from tubulointerstitial injury. However, treatment of wild- type mice with an inhibitory monoclonal antibody to factor B did delay the development of renal failure. These results demonstrate that complement activation in this nonimmune complex- mediated model of progressive renal disease requires an intact alternative pathway. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Univ Zagreb, Univ Hosp Dubrava, Dept Pathol, Zagreb, Croatia. Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Thurman, JM (reprint author), B-115, Aurora, CO 80045 USA. EM Joshua.thurman@uchsc.edu FU NIAID NIH HHS [AI31105]; NIDDK NIH HHS [DK064790] NR 41 TC 23 Z9 23 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2007 VL 293 IS 2 BP F555 EP F564 DI 10.1152/ajprenal.00403.2006 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 196CJ UT WOS:000248459000016 PM 17522263 ER PT J AU Warden, D Trivedi, MH Wisniewski, SR Davis, L Nierenberg, AA Gaynes, BN Zisook, S Hollon, SD Balasubrarnani, GK Howland, R Fava, M Stewart, JW Rush, AJ AF Warden, Diane Trivedi, Madhukar H. Wisniewski, Stephen R. Davis, Lori Nierenberg, Andrew A. Gaynes, Bradley N. Zisook, Sidney Hollon, Steven D. Balasubrarnani, G. K. Howland, Robert Fava, Maurizio Stewart, Jonathan W. Rush, A. John TI Predictors of attrition during initial (Citalopram) treatment for depression: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; REPORT QIDS-SR; CLINICAL-TRIALS; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; RATING-SCALE; DISORDER; SYMPTOMATOLOGY; QUESTIONNAIRE; METAANALYSIS AB Objective: Premature attrition from treatment may lead to worse outcomes and compromise the integrity of clinical trials in major depressive disorder. The purpose of this study was to identify the pretreatment predictors of attrition during acute treatment with citalopram in a large, "real world" clinical trial. Method: A total of 4,041 adult outpatients with nonpsychotic major depressive disorder were enrolled in treatment with citalopram for up to 14 weeks. Attrition was defined as "immediate" (patients who attended a baseline visit only) or "later" (patients who attended at least one postbaseline visit but who dropped out before the 12-week visit). Results: Overall, 26% of enrolled patients dropped out of the acute phase treatment for nonmedical reasons. Of these, 34% dropped out immediately, 59% dropped out by week 12, and 7% dropped out after 12 weeks. Immediate attrition was associated with younger age, less education, and higher perceived mental health functioning. Attrition later in treatment was associated with younger age, less education, and African American race. Experience with more than one episode of depression was associated with less attrition. Conclusions: In clinical trials and clinical practice, several time points in treatment may provide opportunities to engage and encourage populations at higher risk for attrition and populations with high-risk presentation of illness. Additionally, more aggressive forms of treatment implemented earlier in the treatment process in order to increase the likelihood of more rapid efficacy may reduce dropout rates. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. VA Med Ctr, Tuscaloosa, AL USA. Univ Birmingham, Birmingham, AL USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. San Diego VA Med Ctr, San Diego, CA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75230 USA. RP Warden, D (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Diane.Warden@UTSouthwestern.edu RI Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 NR 33 TC 80 Z9 80 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2007 VL 164 IS 8 BP 1189 EP 1197 DI 10.1176/appi.ajp.2007.06071225 PG 9 WC Psychiatry SC Psychiatry GA 199WZ UT WOS:000248727200013 PM 17671281 ER PT J AU Liberzon, I King, AP Britton, JC Phan, KL Abelson, JL Taylor, SF AF Liberzon, Israel King, Anthony P. Britton, Jennifer C. Phan, K. Luan Abelson, James L. Taylor, Stephan F. TI Paralimbic and medial prefrontal cortical involvement in neuroendocrine responses to traumatic stimuli SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CEREBRAL-BLOOD-FLOW; ANTERIOR CINGULATE CORTEX; CORTISOL SECRETION; AMYGDALA; ACTIVATION; FMRI; MODULATION; DEPRESSION; CHALLENGE AB Objective: Hypothalamic-pituitary-adrenal axis activity and cortisol release are consequences of central stress system activation, but they may also influence cognitive and emotional processes within the brain. Despite the importance of central stress response systems, little is known about the specific brain circuits through which psychosocial stimuli activate the hypothalamic-pituitary-adrenal axis and through which cortisol feedback modulates central processing. The authors used [150]H2O positron emission tomography (PET) on subjects with posttraumatic stress disorder (PTSD) to study these circuits. Method: Participants were combat-PTSD patients, combat-exposed healthy comparison subjects, and noncombat-exposed healthy comparison subjects. Participants were scanned using [110]H2O PET while they experienced a series of emotional-induction conditions, which included aversive pictures and autobiographic narratives. Blood samples were obtained 2 minutes before and 5 minutes after each activation scan in order to measure the subjects' plasma adrenocorticotropic hormone and cortisol levels. Results: In voxel-wise analyses, the authors found that adrenocorticotropic hormone responses were covaried with regional cerebral blood flow (rCBF) in the dorsal medial prefrontal cortex, rostral anterior cingulate cortex, and right insula, with some differences between PTSD patients and comparison subjects. Prestimulus cortisol levels covaried with rCBF responses in the rostral anterior cingulate cortex. In combat-PTSD patients only, prestimulus cortisol levels covaried with rCBF in the subgenual anterior cingulate cortex. Conclusions: These findings provide evidence of cortical involvement in hypothalamic-pituitary-ad renal responses to psychological stimuli, specifically implicating the insula, dorsal medial prefrontal cortex, and rostral anterior cingulate cortex. These findings also show, for the first time, that cortisol may modulate activity in specific brain areas such as the rostral and subgenual anterior cingulate cortices. Differential patterns of covariation between combat veterans with and without PTSD potentially implicate the dorsal medial prefrontal cortex and subgenual anterior cingulate cortex as areas of dysregulation in PTSD. C1 Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. VAAAHS, Psychiat Serv, Ann Arbor, MI USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Chicago, Pritzker Sch Med, Dept Psychiat, Chicago, IL 60637 USA. RP Liberzon, I (reprint author), 2753 Rachel Upjohn Bldg,4250 Plymouth Rd, Ann Arbor, MI 48109 USA. EM liberzon@umich.edu RI Taylor, Stephan/A-1211-2007; Britton, Jennifer/J-4501-2013; OI King, Anthony/0000-0002-0764-9625; Liberzon, Israel/0000-0002-4990-556X NR 40 TC 69 Z9 69 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2007 VL 164 IS 8 BP 1250 EP 1258 DI 10.1176/appi.ajp.2007.06081367 PG 9 WC Psychiatry SC Psychiatry GA 199WZ UT WOS:000248727200021 PM 17671289 ER PT J AU Silva, EG Young, RH AF Silva, Elvio G. Young, Robert H. TI Endometrioid neoplasms with clear cells - A report of 21 cases in which the alteration is not of typical secretory type SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; neoplasms; clear cells; endometrioid carcinoma ID CORD-STROMAL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; CARCINOMA; OVARY; ADENOCARCINOMA; CONFUSION AB The presence of clear cells in genital tract neoplasms often reflexly prompts the diagnosis of a clear cell tumor but clear cells may be seen in many other neoplasms. In one such, those of endometrioid type, they are well known and generally readily characterized when they have the secretory pattern that recapitulates the well-known morphology of early secretory endometrium. In this report, we describe various clear cell morphologies. some possibly related to the secretory variant, but others not, and all potentially the source of significant diagnostic difficulty. We reviewed 21 endometrioid tumors that occurred in patients from 27 to 88 (median 64) years. Most had an adnexal mass (13) or abdominal swelling (4), but 4 presented with vaginal bleeding,. One tumor formed a cystic mass in the pelvis, I tumor involved the right fallopian tube, I the endometrium, and 18 the ovary. One tumor was a cystadenofibroma. I a borderline tumor. and 19 were adenocarcinomas. Twelve patients had stage 1, 4 stage 111, 1 stage IV, and 4 were unstaged. One patient who had a previous hysterectomy and salpingo-oophorectomy underwent resection of a cystic pelvic mass; others all were treated with abdominal hysterectomy and salpingo-oophorectomy. All the neoplasms had the typical architecture of endometrioid tumors but differed markedly in their cytoplasmic features. In 18 of the tumors at least one-third of the cells had clear cytoplasm and 3 had only clear cells. The clear cytoplasm varied from foamy to empty and the nuclei had a variable location, basilar, central, and apical. The clear cells were associated with squamous differentiation in only I case in which the change appeared hydropic. By immunohistocytochemistry, the clear cells were focally positive for epithelial markers in most cases but in some cases one or more of these immunostains were negative. Tubulocystic, solid, and papillary patterns of clear cell carcinoma were absent. Periodic acid-Schiff was focally positive for glycogen in the cytoplasm in 5 cases. Although a few cases had a focal slight resemblance to secretory endometrioid carcinoma most did not and the orderly morphology of classic secretory carcinoma was noteworthy for its absence. The nature of the cytoplasmic clarity is usually uncertain but is likely variably owing to lipid, mucin or glycogen accumulation, or is a hydropic change. The distinction from clear cell carcinoma depends on awareness of this unusual variant of endometrioid neoplasia and a lack of the distinctive patterns of clear cell carcinoma; at this time, special studies, including immunohistochemistry, do not aid significantly although certainly negative reactions, such as for thyroglobulin protein (arguing against clear cell struma ovarii) may play a role in some differential diagnostic considerations. There are prognostic and therapeutic implications in the distinction with clear cell carcinoma. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Holer Wright Pathol Labs, Boston, MA 02115 USA. RP Silva, EG (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd,Unit 85, Houston, TX 77030 USA. EM esilva@mdanderson.org NR 14 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2007 VL 31 IS 8 BP 1203 EP 1208 DI 10.1097/PAS.0b013e3180339ed7 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 195GP UT WOS:000248400800010 PM 17667544 ER PT J AU Oliva, E de Leval, L Soslow, RA Herens, C AF Oliva, Esther de Leval, Laurence Soslow, Robert A. Herens, Christian TI High frequency of JAZF1-JJAZ1 gene fusion in endometrial stromal tumors with smooth muscle differentiation by interphase FISH detection SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial stromal tumors; smooth muscle differentiation; JAZF1-JJAZ1 fusion gene; FISH; differential diagnosis ID UNUSUAL HISTOLOGIC FEATURES; FEMALE GENITAL-TRACT; SOFT-TISSUE TUMORS; OF-THE-LITERATURE; SEX-CORD TUMORS; MESENCHYMAL TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; INTRAVENOUS LEIOMYOMATOSIS; GLANDULAR DIFFERENTIATION; CELLULAR LEIOMYOMA AB The most common cytogenetic alteration observed in low-grade endometrial stromal tumors (EST) is the t(7;17)(p15.-q21) translocation, resulting in the fusion of the JAZF1 and JJAZ1 genes. By reverse-transcription polymerase chain reaction, the translocation has been detected overall in one-third of ESTs. but only rarely in its variants. The purpose of this study was to develop a fluorescence in situ hybridization assay for detection of this translocation using archival paraffin-embedded samples of ESTs with smooth muscle differentiation and to assess the nature of the smooth Muscle component of these tumors. Representative paraffin blocks of 9 endometrial stromal nodules and I low-grade endometrial stromal sarcoma were collected for the study. In I case, the block selected also contained areas of sex cordlike differentiation. A fluorescence in situ hybridization probe set was designed to detect the t(7;17)(p15;q12) on tissue sections. Six Out of 10 collected ESTs were assessable. Fusion signals were detected in 3 out of 6 cases (50%) in both the conventional endometrial stromal and the smooth muscle components of the tumors. The tumor sample with sex cordlike differentiation harbored the fusion signal in all the 3 components. Out-results Support the contention that the endometrial stromal and smooth muscle components of these tumors have the same ori.-in, either from a common precursor cell with pluripotential differentiation or from endometrial stromal cells that have undergone smooth muscle metaplasia. Our results indicate that the detection of this chromosomal abnormality can be used to diagnose ESTs with smooth muscle differentiation when the smooth muscle component is predominant. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. CHU Sart Tilman, Dept Pathol, B-4000 Liege, Belgium. CHU Sart Tilman, Dept Human Genet, B-4000 Liege, Belgium. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM eoliva@partners.org NR 79 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2007 VL 31 IS 8 BP 1277 EP 1284 DI 10.1097/PAS.0b013e318031f012 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 195GP UT WOS:000248400800020 PM 17667554 ER PT J AU Baker, JF Schumacher, HR Krishnan, E AF Baker, Joshua F. Schumacher, H. Ralph Krishnan, Eswar TI Serum uric acid level and risk for peripheral arterial disease: Analysis of data from the multiple risk factor intervention trial SO ANGIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; CARDIOVASCULAR-DISEASE; SYSTOLIC HYPERTENSION; INDEPENDENT PREDICTOR; EVENTS; STROKE; URATE; ATHEROSCLEROSIS; METABOLISM; MORTALITY AB Although several studies report an association between hyperuricemia and coronary artery disease, little is known about the effect of hyperuricemia and gout on the risk of peripheral arterial disease (PAD). Data on 283 incident clinical cases of PAD during a randomized controlled trial of multiple cardiovascular risk factor intervention are evaluated. The serum uric acid levels among these individuals are compared with those of individuals who did not develop PAD during the study period. Multivariate logistic regression analyses measure the risk of developing PAD associated with higher levels of serum uric acid after adjusting for the effect of traditional vascular risk factors. Age and smoking are independently associated with development of PAD, with odds ratios of 1.08 (95% confidence interval [CI], 1.06-1.09) and 3.83 (95% CI, 2.49-5.91) per year, respectively. Hyperuricemia (serum uric acid level, > 7.0 mg/dL) is an independent risk factor, with an odds ratio of 1.23, but the confidence interval of the estimate is wide (95% CI, 0.98-1.54). In this multivariate model, a history of gout was associated with an odds ratio of 1.33 (95% CI, 1.07-1.66). Serum uric acid level is independently associated with a higher (but statistically nonsignificant) risk of PAD. A history of gouty arthritis is an independent and statistically significant predictor of incidence of PAD even after adjustment for the effect of underlying hyperuricemia. C1 Univ Pittsburgh, Dept Med, Div Rheumatol, Pittsburgh, PA 15261 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Krishnan, E (reprint author), Univ Pittsburgh, Dept Med, Div Rheumatol, S709 BST S,3500 Terrace St, Pittsburgh, PA 15261 USA. EM Arthritis.MD@gmail.com RI KRISHNAN, ESWAR/A-1072-2009 NR 33 TC 44 Z9 47 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD AUG-SEP PY 2007 VL 58 IS 4 BP 450 EP 457 DI 10.1177/0003319707303444 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 204EH UT WOS:000249026000009 PM 17875958 ER PT J AU Krauss, B Hess, DR AF Krauss, Baruch Hess, Dean R. TI Capnography for procedural sedation and analgesia in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID CARBON-DIOXIDE; PULSE OXIMETRY; ESOPHAGEAL INTUBATION; EXPIRATORY CAPNOGRAM; CONSCIOUS SEDATION; TIDAL VOLUME; DEAD SPACE; CHILDREN; OXYGEN; VENTILATION AB Although standard of care for patient safety monitoring in anesthesia, capnography is not routinely used for emergency department procedural sedation and analgesia. We discuss the use of capnography as a diagnostic monitoring modality for procedural sedation and analgesia focusing on the physiology and interpretation of the CO2 waveform, and recognition of normal, abnormal, and drug-induced ventilatory patterns. C1 Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Krauss, B (reprint author), Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM baruch.krauss@childrens.harvard.edu NR 48 TC 66 Z9 66 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2007 VL 50 IS 2 BP 172 EP 181 DI 10.1016/j.annemergmed.2006.10.016 PG 10 WC Emergency Medicine SC Emergency Medicine GA 197JB UT WOS:000248549800012 PM 17222941 ER PT J AU Zabetian, CP Hutter, CM Factor, SA Nutt, JG Higgins, DS Griffith, A Roberts, JW Leis, BC Kay, DM Yearout, D Montimurro, JS Edwards, KL Samii, A Payami, H AF Zabetian, Cyrus P. Hutter, Carolyn M. Factor, Stewart A. Nutt, John G. Higgins, Donald S. Griffith, Alida Roberts, John W. Leis, Berta C. Kay, Denise M. Yearout, Dora Montimurro, Jennifer S. Edwards, Karen L. Samii, Ali Payami, Haydeh TI Association analysis of MAPT H1 haplotype and subhaplotypes in Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; TAU-GENE HAPLOTYPE; LINKAGE DISEQUILIBRIUM; CORTICOBASAL DEGENERATION; ALPHA-SYNUCLEIN; POLYMORPHISM; POPULATION; DEMENTIA; SUSCEPTIBILITY; METAANALYSIS AB Objective: An inversion polymorphism of approximately 900kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene defines two haplorype clades, HI and H2. Several small case-control studies have observed a marginally significant excess of the H1/H1 diplotype among patients with Parkinson's disease (PD), and one reported refining the association to a region spanning exons 1 to 4 of MAPT. We sought to replicate these findings. Methods: We genotyped 1,762 PD patients and 2,010 control subjects for a single nucleotide polymorphism (SNP) that differentiates the HI and H2 clades. We also analyzed four SNPs that define subhaplotypes within HI previously reported to associate with PD or other neurodegenerative disorders. Results: After adjusting for age, sex, and site, we observed a robust association between the H1/H1 diplotype and PD risk (odds ratio for H1/H1 vs H1/H2 and H2/H2, 1.46; 95% confidence interval, 1.25-1.69; p = 8 x 10(-7)). The effect was evident in both familial and sporadic subgroups, men and women, and early- and late-onset disease. Within H1/H1 individuals, there was no significant difference between cases and control subjects in the overall frequency distribution of Hi subhaplotypes. Interpretation: Our data provide strong evidence that the H I clade, which contains MAPT and several other genes, is a risk factor for PD. However, attributing this finding to variants within a specific region of MAPT is premature. Thorough fine-mapping of the H1 clade in large numbers of individuals is now needed to identify the underlying functional variant(s) that alter susceptibility for PD. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. Evergreen Hosp Med Ctr, Booth Gardener Parkinsons Care Ctr, Kirksville, WA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY USA. Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306; Kay, Denise/0000-0002-9928-2698 FU NIA NIH HHS [N1A P30 AG008017, P30 AG008017]; NINDS NIH HHS [K08 NS044138, K08 NS044138-04, R01 NS036960] NR 44 TC 75 Z9 75 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2007 VL 62 IS 2 BP 137 EP 144 DI 10.1002/ana.21157 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 215TI UT WOS:000249831500007 PM 17514749 ER PT J AU Bilimoria, KY Bentrem, DJ Ko, CY Stewart, AK Winchester, DP Talamonti, MS AF Bilimoria, Karl Y. Bentrem, David J. Ko, Clifford Y. Stewart, Andrew K. Winchester, David P. Talamonti, Mark S. TI National failure to operate on early stage pancreatic cancer SO ANNALS OF SURGERY LA English DT Article ID LONG-TERM SURVIVAL; HOSPITAL VOLUME; ADMINISTRATIVE DATA; UNITED-STATES; CONSECUTIVE PANCREATICODUODENECTOMIES; DUCTAL ADENOCARCINOMA; GENERAL-POPULATION; COLORECTAL-CANCER; LAST DECADE; MORTALITY AB Background: Despite studies demonstrating improved outcomes, pessimism persists regarding the effectiveness of surgery for pancreatic cancer. Our objective was to evaluate utilization of surgery in early stage disease and identify factors predicting failure to undergo surgery. Methods: Using the National Cancer Data Base (1995-2004), 9559 patients were identified with potentially resectable tumors (pretreatment clinical Stage I:T1N0M0 and T2N0M0). Multivariate models were employed to identify factors predicting failure to undergo surgery and assess the impact of pancreatectomy on survival. Results: Of clinical Stage I patients 71.4% (6823/9559) did not undergo surgery; 6.4% (616/9559) were excluded due to comorbidities; 4.2% (403/9559) refused surgery; 9.1% (869/9559) were excluded due to age; and 38.2% (3,644/9559) with potentially resectable cancers were classified as "not offered surgery." Of the 28.6% (2736/9559) of patients who underwent surgery, 96.0% (2630/2736) underwent pancreatectomy, and 4.0% (458/2736) had unresectable tumors. Patients were less likely to undergo surgery if they were older than 65 years, were black, were on Medicare or Medicaid, had pancreatic head lesions, earned lower annual incomes, or had less education (P < 0.0001). Patients were less likely to receive surgery at low-volume and community centers. Patients underwent surgery more frequently at National Cancer Institute/National Comprehensive Cancer Network-designated cancer centers (P < 0.0001). Patients who were not offered surgery had significantly better survival than those with Stage III or IV disease but worse survival than patients who underwent pancreatectomy for Stage I disease (P < 0.0001). Conclusions: This is the first study to characterize the striking under-use of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery. C1 Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. Amer Coll Surg, Canc Programs, Natl Canc Data Base, Chicago, IL USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Evanston NW Healthcare, Dept Surg, Evanston, IL USA. RP Talamonti, MS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, 675 N St Clair St,Galter 10-105, Chicago, IL 60611 USA. EM mtalamonti@nmff.org RI qiao, zhixin/I-3408-2012; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 55 TC 215 Z9 222 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 2007 VL 246 IS 2 BP 173 EP 180 DI 10.1097/SLA.0b013e3180691579 PG 8 WC Surgery SC Surgery GA 194TA UT WOS:000248365500003 PM 17667493 ER PT J AU Weiner, M Burman, W Luo, CC Peloquin, CA Engle, M Goldberg, S Agarwal, V Vernon, A AF Weiner, Marc Burman, William Luo, Chi-Cheng Peloquin, Charles A. Engle, Melissa Goldberg, Stefan Agarwal, Vipin Vernon, Andrew TI Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; IN-VIVO; PHARMACOKINETICS; TUBERCULOSIS; INDUCTION; CONSEQUENCES; SPARFLOXACIN; HAPLOTYPES; VITRO AB Treatment regimens combining moxifloxacin and rifampin for drug-susceptible tuberculosis are being studied intensively. However, rifampin induces enzymes that transport and metabolize moxifloxacin. We evaluated the effect of rifampin and the human multidrug resistance gene (MDR1) C3435T polymorphisms (P-glycoprotein) on moxifloxacin pharmacokinetic parameters. This was a single-center, sequential design study with 16 volunteers in which sampling was performed after four daily oral doses of moxifloxacin (400 mg) and again after 10 days of combined rifampin (600 mg) and moxifloxacin. After daily coadministration of rifampin, the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for moxifloxacin decreased 27%. Average bioequivallence between moxifloxacin coadministered with rifampin and moxifloxacin alone was not demonstrated: the ratio of geometric means (RGM) of the moxifloxacin AUC(0-24) was 73.3 (90% confidence intervals [CI], 64.3, 83.5) (total P value, 0.87 for two one-sided t tests). Peak moxifloxacin concentrations, however, were equivalent: the RGM of the maximum concentration of the drug in serum was 93.6 (90% Cl, 80.2, 109.3) (total P value, 0.049). Concentrations of the sulfate conjugate metabolite of moxifloxacin were increased twofold following rifampin coadministration (AUC(0-24), 1.29 versus 2.79 mu g - h/ml). Concomitant rifampin administration resulted in a 27% decrease in the mean moxifloxacin AU(0-24),-,, and a marked increase in the AUC(0-24),, of the microbiologically inactive M1 metabolite. Additional studies are required to understand the clinical significance of the moxifloxacin-rifampin interaction. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Denver Publ Hlth, Denver, CO 80204 USA. Natl Jewish Med, Denver, CO 80206 USA. Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA 30333 USA. NE Bioanalyt Labs, Hamden, CT USA. RP Weiner, M (reprint author), VAMC, Div Infect Dis 111F, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu FU NCRR NIH HHS [M01 RR01346, M01 RR001346] NR 20 TC 57 Z9 57 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2007 VL 51 IS 8 BP 2861 EP 2866 DI 10.1128/AAC.01621-06 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 196ZZ UT WOS:000248523700027 PM 17517835 ER PT J AU Fuchs, BB Tegos, GP Hamblin, MR Mylonakis, E AF Fuchs, Beth Burgwyn Tegos, George P. Hamblin, Michael R. Mylonakis, Eleftherios TI Susceptibility of Cryptococcus neoformans to photodynamic inactivation is associated with cell wall integrity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GTP-BINDING PROTEIN; GRAM-NEGATIVE BACTERIA; MAP KINASE PATHWAY; SACCHAROMYCES-CEREVISIAE; 1,3-BETA-GLUCAN SYNTHASE; MK-0991 L-743,872; YEAST PROTEIN; THERAPY; RHO1; PHOTOINACTIVATION AB Photodynamic therapy is a rapidly developing antimicrobial technology which combines a nontoxic photoactivatable dye or photosensitizer with harmless visible light of the correct wavelength to excite the dye to its reactive triplet state to generate reactive oxygen species toxic to cells. In this report we present evidence that the fungal pathogen Cryptococcus neoformans is susceptible to photodynamic inactivation by use of a polycationic conjugate of polyethyleneimine and the photosensitizer chlorin(e6). A C neoformans rom2 mutant, with a mutation involving a putative Rhol guanyl nucleotide exchange factor that is part of the protein kinase C-cell wall integrity pathway, demonstrated a compromised cell wall and less (1,3)beta-D glucan than the wild-type strain and increased accumulation of PEI-ce6 as assessed by fluorescence uptake and confocal microscopy. Interestingly, C neoformans rom2 was hypersusceptible to photodynamic inactivation and coincubation of wild-type C neoformans strain KN99 alpha with caspofungin-enhanced photoinactivation. These studies demonstrated that C neoformans is sensitive to photodynamic therapy and illustrated the significance of cell wall integrity in microbial susceptibility to antimicrobial photodynamic inactivation. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02144 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02144 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 5 Fruit St,GRJ-504, Boston, MA 02144 USA. EM emylonakis@partners.org RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [K08 AI063084, K08 AI63084, R01 AI050875, R01 AI050875-05A1]; NIDDK NIH HHS [DK43351, DK57521, P30 DK043351, P30 DK057521] NR 48 TC 44 Z9 46 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2007 VL 51 IS 8 BP 2929 EP 2936 DI 10.1128/AAC.00121-07 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 196ZZ UT WOS:000248523700036 PM 17548495 ER PT J AU Kirkpatrick, WR Najvar, LK Bocanegra, R Patterson, TF Graybill, JR AF Kirkpatrick, William R. Najvar, Laura K. Bocanegra, Rosie Patterson, Thomas F. Graybill, John R. TI New guinea pig model of cryptococcal meningitis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; VORICONAZOLE; FLUCONAZOLE; EFFICACY AB We developed a guinea pig model of cryptococcal meningitis to evaluate antifungal agents. Immunosuppressed animals challenged intracranially with. Cryptococcus neoformans responded to fluconazole and voriconazole. Disease was monitored by serial cerebrospinal fluid (CSF) cultures and quantitative organ cultures. Our model produces disseminating central nervous system disease and responds to antifungal therapy. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr 7781, San Antonio, TX 78229 USA. EM kirkpatrick@uthscsa.edu FU NIAID NIH HHS [N01AI25475, N01 AI25475] NR 9 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2007 VL 51 IS 8 BP 3011 EP 3013 DI 10.1128/AAC.00085-07 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 196ZZ UT WOS:000248523700053 PM 17562797 ER PT J AU Dougherty, CM Johnston, SK Thompson, EA AF Dougherty, Cynthia M. Johnston, Sandra K. Thompson, Elaine Adams TI Reliability and validity of the self-efficacy expectations and outcome expectations after Implantable Cardioverter defibrillator implantation scales SO APPLIED NURSING RESEARCH LA English DT Article ID ARTERY BYPASS-SURGERY; CARDIAC REHABILITATION; HUMAN AGENCY; VALIDATION; EXERCISE; CONFIDENCE; INFARCTION; CARDIOLOGY AB The purpose of this study was to assess the reliability and validity characteristics of two new scales that measure self-efficacy expectations (Self-Efficacy Expectations After Implantable Cardioverter Defibrillator Implantation Scale [SE-ICD]) and outcome expectations (Outcome Expectations After ICD Implantation Scale [OE-ICD]) in survivors (N = 168) of sudden cardiac arrest, all of whom received an ICD. Cronbach's alpha reliability demonstrated good internal consistency (SE-ICD alpha =.93 and OE-ICD alpha =.81). Correlations with other self-efficacy instruments (general self-efficacy and social self-efficacy) were consistently high. The instruments were responsive to change across time with effect sizes of .46 for SE-ICD and .26 for OE-ICD. These reliable, valid, and responsive instruments for measurement of self-efficacy expectations and outcome expectations after an ICD can be used in research and clinical settings. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Nursing, Psychosocial & Community Hlth, Seattle, WA 98195 USA. RP Dougherty, CM (reprint author), Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. EM cindyd@u.washington.edu FU NINR NIH HHS [R01 NR004766, R01 NR004766-01A1, R01 NR04766] NR 31 TC 11 Z9 11 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD AUG PY 2007 VL 20 IS 3 BP 116 EP 124 DI 10.1016/j.apnr.2007.04.004 PG 9 WC Nursing SC Nursing GA 203IN UT WOS:000248968400003 PM 17693214 ER PT J AU Tsao, H AF Tsao, Hensin TI Genetics and genomics in melanoma SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ Med Sch, Massachusetts Gen Hosp, Dept Dermatol MGH Melanoma &Pigemented Ctr, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD AUG PY 2007 VL 299 IS 5-6 BP 296 EP 297 PG 2 WC Dermatology SC Dermatology GA 200NW UT WOS:000248771100083 ER PT J AU Colby, KA Chang, DF Stulting, D Lane, SS AF Colby, Kathryn A. Chang, David F. Stulting, Doyle Lane, Stephen S. TI Surgical placement of an optical prosthetic device for end-stage macular degeneration - The implantable miniature telescope SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CATARACT-SURGERY AB Objective: To describe the surgical procedure for placement of an implantable telescope prosthesis for endstage age-related macular degeneration. Methods: As part of a phase 2/3 clinical trial for patients with bilateral, irreversible age-related macular degeneration, the optimal procedure for monocular placement of the telescope prosthesis was determined. Results: Because of the unique configuration of the telescope prosthesis, proper wound construction, anterior chamber management, and device insertion after phacoemulsification are critical for successful surgery. Conclusion: A unique surgical technique ensures appropriate placement of the telescope prosthesis, while reducing surgical trauma to the corneal endothelium. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. Emory Univ, Emory Vis Ctr, Atlanta, GA 30322 USA. Associated Eye Care, Stillwater, MN USA. RP Colby, KA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,Ste 808, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 8 TC 8 Z9 8 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2007 VL 125 IS 8 BP 1118 EP 1121 DI 10.1001/archopht.125.8.1118 PG 4 WC Ophthalmology SC Ophthalmology GA 197XO UT WOS:000248590600017 PM 17698761 ER PT J AU Davidson, B AF Davidson, Bruce TI Vocal fold medialization in children - Injection laryngoplasty, thyroplasty, or nerve reinnervation? SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CORD PARALYSIS; CALCIUM HYDROXYLAPATITE; MICRONIZED ALLODERM; LONG; AUGMENTATION; MANAGEMENT AB The program in Otolaryngology- Head and Neck surgery at Georgetown University Hospital is offering a unique opportunity to a BC/BE physician with fellowship training in Laryngology to join our program. This is a full time academic position which will allow the appropriate candidate to develop a practice focused on the care of patients with voice and swallowing disorders at two of the premier institutions in metropolitan Washington, Georgetown University Hospital and the Washington Hospital Center. The candidate will be active in resident and medical student education and in clinical research. Georgetown University Hospital is the largest academic medical center in the Washington area. Washington Hospital Center is the largest not-forprofit teaching hospital in metropolitan Washington, DC. For over 25 years, these two hospitals have served as the major teaching institutions for the Georgetown Otolaryngology Residency Program. Both hospitals are part of MedStar Health, a $2.7 billion not-for-profit healthcare organization and a community-based network of seven hospitals and other healthcare services in the Baltimore-Washington region. This network is the largest health system and one of the largest employers in the Baltimore/Washington area, with more than 23,000 employees and 4,600 affiliated physicians, all of whom support MedStar Health's patient-first philosophy. This philosophy combines patient care, compassion and clinical excellence with an emphasis on customer service. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Georgetown Univ Hosp, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. RP Davidson, B (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM davidsob@georgetown.edu NR 25 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2007 VL 133 IS 8 BP 767 EP 771 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 197XP UT WOS:000248590700005 ER PT J AU Pletcher, SD Metson, R AF Pletcher, Steven D. Metson, Ralph TI Endoscopic optic nerve decompression for nontraumatic optic neuropathy SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article AB Objective: To determine the efficacy of endoscopic optic nerve decompression for the treatment of patients with nontraumatic optic neuropathy. Design: Retrospective case series. Setting: Academic medical center. Patients: Ten optic nerve decompressions were performed on 7 patients with nontraumatic optic neuropathy caused by various pathologic entities, including meningioma, lymphangioma, fibro-osseous lesions (fibrous dysplasia and osteoma), mucopyocele, and Graves orbitopathy. Interventions: Endoscopic instrumentation was used in a transnasal fashion to decompress the optic nerve. Main Outcome Measures: Visual acuity and complication rates. Results: Mean visual acuity improved from 20/300 preoperatively to 20/30 after surgery. Visual acuity improved by at least 2 lines on the Snellen chart following 7 of the 10 decompressions. Median operative time was 133 minutes, and median length of stay was less than 24 hours. Complications were limited to postoperative hyponatremia and corneal abrasions, both of which resolved with conservative therapy. Mean follow-up time was 6.1 months. Conclusion: Endoscopic optic nerve decompression appears to be an effective treatment for restoring visual acuity in select patients who present with compressive optic neuropathy.Main Outcome Measures: Visual acuity and complication rates. Results: Mean visual acuity improved from 20/300 preoperatively to 20/30 after surgery. Visual acuity improved by at least 2 lines on the Snellen chart following 7 of the 10 decompressions. Median operative time was 133 minutes, and median length of stay was less than 24 hours. Complications were limited to postoperative hyponatremia and corneal abrasions, both of which resolved with conservative therapy. Mean follow-up time was 6.1 months. Conclusion: Endoscopic optic nerve decompression appears to be an effective treatment for restoring visual acuity in select patients who present with compressive optic neuropathy. C1 Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Pletcher, SD (reprint author), Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, 400 Parnassus Ave,ACC 7th Floor, San Francisco, CA 94143 USA. EM spletcher@ohns.ucsf.edu NR 12 TC 13 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2007 VL 133 IS 8 BP 780 EP 783 DI 10.1001/archotol.133.8.780 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 197XP UT WOS:000248590700008 PM 17709616 ER PT J AU Tomlinson, JS Jain, S Bentrem, DJ Sekeris, EG Maggard, MA Hines, OJ Reber, HA Ko, CY AF Tomlinson, James S. Jain, Sushma Bentrem, David J. Sekeris, Evangelos G. Maggard, Melinda A. Hines, O. Joe Reber, Howard A. Ko, Clifford Y. TI Accuracy of staging node-negative pancreas cancer - A potential quality measure SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 18, 2007 CL Kohala Coast, HI SP Pacific Coast Surg Assoc ID ADJUVANT COMBINED RADIATION; CURATIVE RESECTION; LYMPH-NODES; PROGNOSTIC INDICATORS; ADENOCARCINOMA; PANCREATICODUODENECTOMY; SURVIVAL; NUMBER; HEAD; LYMPHADENECTOMY AB Objective: To determine the optimal number of lymph nodes to examine for accurate staging of node-negative pancreatic adenocarcinoma after pancreaticoduodenectomy. Design, Setting, and Patients: Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program (1988-2002) were used to identify 3505 patients who underwent pancreaticoduodenectonny for adenocarcinoma of the pancreas, including 1150 patients who were pathologically node negative (pN0) and 584 patients with a single positive node (pN1a). Perioperative deaths were excluded. Univariate and multivariate survival analyses were performed. Main Outcome Measure: Examination of 15 lymph nodes appears to be optimal for accurate staging of nodenegative adenocarcinoma of the pancreas after pancreaticoduodenectomy. Results: The number of nodes examined ranged from 1 to 54 (median, 7 examined nodes). Univariate survival analysis demonstrated that dichotomizing the pN0 cohort on 15 or more examined lymph nodes resulted in the most statistically significant survival difference (log-rank chi(2) = 14.49). Kaplan-Meier survival curves demonstrated a median survival difference of 8 months (P < .001) in favor of the patients who had 15 or more examined nodes compared with patients with fewer than 15 examined nodes. Multivariate analysis validated that having 15 or more examined nodes was a statistically significant predictor of survival (hazard ratio, 0.63; 95% confidence interval, 0.49-0.80; P < .0001). Furthermore, a multivariate model based on the survival benefit of each additional node evaluated in the pN0 cohort demonstrated only a marginal survival benefit for analysis of more than 15 nodes. Approximately 90% of the pN1a cohort was identified with examination of 15 nodes. Conclusions: Examination of 15 lymph nodes appears to be optimal to accurately stage node-negative adenocarcinoma of the pancreas after pancreaticoduodenectomy. Furthermore, evaluation of at least 15 lymph nodes of a pancreaticoduodenectomy specimen may serve as a quality measure in the treatment of pancreatic adenocarcinoma. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Surg Outcomes & Qual, Dept Surg, Los Angeles, CA USA. Northwestern Univ, Div Surg Oncol, Dept Surg, Chicago, IL 60611 USA. RP Tomlinson, JS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM james.tomlinson@va.gov NR 29 TC 57 Z9 60 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2007 VL 142 IS 8 BP 767 EP 773 DI 10.1001/archsurg.142.8.767 PG 7 WC Surgery SC Surgery GA 199UR UT WOS:000248721200017 PM 17709731 ER PT J AU Raffel, OC Tearney, GJ Gauthier, DD Halpern, EF Bouma, BE Jang, IK AF Raffel, O. Christopher Tearney, Guillermo J. Gauthier, Denise DeJoseph Halpern, Elkan F. Bouma, Brett E. Jang, Ik-Kyung TI Relationship between a systemic inflammatory marker, plaque inflammation, and plaque characteristics determined by intravascular optical coherence tomography SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE optical coherence tomography; atherosclerosis; thin-cap fibroatheroma; leukocytes; macrophage ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; MULTIPLE COMPLEX STENOSES; C-REACTIVE PROTEIN; ATHEROSCLEROTIC PLAQUES; ARTERY-DISEASE; LEUKOCYTE COUNT; RISK-FACTORS; MORPHOLOGY; RUPTURE AB Objective - The purpose of this study was to evaluate the relationships between the peripheral white blood cell (WBC) count, local plaque fibrous cap macrophage density, and the morphological features and presence of thin-cap fibroatheromas (TCFA) identified by optical coherence tomography ( OCT). Methods and Results - OCT was performed in patients undergoing catheterization. Images were analyzed using validated criteria for plaque characteristics. Baseline WBC count correlated with macrophage density ( r = 0.483, P = 0.001). Both parameters were associated with lipid-rich plaque and correlated inversely with plaque fibrous cap thickness ( r = - 0.547 for macrophage density and -0.423 for WBC count, P < 0.015). Plaques classified as TCFA had a higher median macrophage density than non-TCFA plaques ( 7.4 versus 4.99, P < 0.001). Patients with TCFA had a higher WBC count compared with those without TCFA (11.0 versus 7.9, P = 0.007). Receiver operator curves for WBC count, macrophage density, and these combined parameters for prediction of TCFA showed the area under the curves were 0.88, 0.91, and 0.97 ( P < 0.001), respectively. Conclusion - This study provides the first in vivo data linking the peripheral WBC count, plaque fibrous cap macrophage density, and the characteristics and presence of TCFA. Macrophage density correlated with the WBC count, and both parameters independently and particularly in combination predict the presence of TCFA. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org FU NHLBI NIH HHS [R01 HL076398, R01 HL076398-03] NR 37 TC 67 Z9 72 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2007 VL 27 IS 8 BP 1820 EP 1827 DI 10.1161/ATVBAHA.107.145987 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 192BR UT WOS:000248176200022 PM 17541021 ER PT J AU Pineles, SL Shipherd, JC Welch, LP Yovel, I AF Pineles, Suzanne L. Shipherd, Jillian C. Welch, Lisa P. Yovel, Iftah TI The role of attentional biases in PTSD: Is it interference or facilitation? SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE posttraumatic stress disorder; attentional bias; attentional interference; attentional facilitation ID POSTTRAUMATIC-STRESS-DISORDER; EMOTIONAL STROOP TASK; SELECTIVE ATTENTION; FACIAL EXPRESSIONS; SOCIAL PHOBIA; FEAR; ANXIETY; THREAT; FACES; DISENGAGEMENT AB Although attentional biases have been demonstrated in individuals with posttraumatic stress disorder (PTSD), the cognitive methodologies used have not allowed for disambiguation of two types of attentional biases. It remains unclear if PTSD involves difficulty disengaging attention from threatening stimuli (interference) or facilitated detection. To differentiate between attentional interference and facilitation, 57 male Vietnam-era veterans (30 High PTSD and 27 Low PTSD) completed a visual search task with a lexical decision component. High PTSD veterans who engaged in the interference task first showed increased interference to threat-relevant words relative to Low PTSD veterans. However, no evidence was found for facilitated detection of threatening stimuli in PTSD. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. RP Pineles, SL (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM suzanne.pincles@va.gov NR 26 TC 48 Z9 49 U1 7 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 2007 VL 45 IS 8 BP 1903 EP 1913 DI 10.1016/j.brat.2006.08.021 PG 11 WC Psychology, Clinical SC Psychology GA 202AQ UT WOS:000248874300016 PM 17049337 ER PT J AU Buffon, A Wink, MR Ribeiro, BV Casali, EA Libermann, TA Zerbini, LF Robson, SC Sarkis, JJF AF Buffon, A. Wink, M. R. Ribeiro, B. V. Casali, E. A. Libermann, T. A. Zerbini, L. F. Robson, S. C. Sarkis, J. J. F. TI NTPDase and 5 ' ecto-nucleotidase expression profiles and the pattern of extracellular ATP metabolism in the Walker 256 tumor SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Walker 256 tumor; NTPDases; 5'-nucleotidase; adenine nucleotides; cancer ID ECTO-ATPASE; CARCINOMA-CELLS; ADENOSINE-TRIPHOSPHATE; GROWTH-INHIBITION; CANCER-CELLS; KAPPA-B; APOPTOSIS; INVOLVEMENT; RECEPTOR; ECTO-5'-NUCLEOTIDASE AB In this study, we evaluated the NTPDases and ecto-5'-nucleotidase (CD73) expression profiles and the pattern of adenine nucleotide hydrolysis in rats submitted to the Walker 256 tumor model, 6, 10 and 15 days after the subcutaneous inoculation. Using RT-PCR analysis, we identified mRNA for all of the members of the ecto-nucleoside triphosphate diphosphohydrolase family investigated and a 5'-nucleotidase. By quantitative real-time PCR, EntpdI (Cd39) and Entpd2 (Cd39L1) and CD73 were identified as the dominant genes expressed by the Walker 256 tumor, at all times studied. Extracellular adenine nucleotide hydrolysis by the Walker 256 tumor was estimated by HPLC analysis. Rapid hydrolysis of extracellular ATP by the tumor cells was observed, leading to the formation of adenosine and inosine in cells obtained from solid tumors at 6 and 10 days after inoculation. Cells obtained from solid tumors at 15 days of growth presented high levels of AMP and presented adenosine as a final product after 90 min of incubation. Results demonstrate that the presence of NTPDases and 5'-nucleotidase enzymes in Walker 256 tumor cells may be important for regulation of the extracellular adenine nucleotides/adenine nucleoside ratio, therefore leading to tumor growth. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, BR-90035003 Porto Alegre, RS, Brazil. FFFCMPA, Dept Ciencias Fisiol, Porto Alegre, RS, Brazil. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, BIDMC Genom Ctr, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dana Farber Canc Proteom Core, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. RP Buffon, A (reprint author), Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, Rua Ramiro Barcelos 2600 ANEXO, BR-90035003 Porto Alegre, RS, Brazil. EM debuffon@redemeta.com.br RI Zerbini, Luiz /B-7720-2015; OI Libermann, Towia/0000-0002-4006-8179 FU NHLBI NIH HHS [R01 HL063972, R01 HL063972-08] NR 50 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD AUG PY 2007 VL 1770 IS 8 BP 1259 EP 1265 DI 10.1016/j.bbagen.2007.05.004 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 196RZ UT WOS:000248501000021 PM 17574764 ER PT J AU Avruch, J AF Avruch, Joseph TI MAP kinase pathways: The first twenty years SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE MAP kinase; ERK; JNK; p38; SAPK; protein phosphorylation; protein kinase cascade; signal transduction; docking site; scaffold protein; transcriptional regulation; cell fate ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; RABBIT SKELETAL-MUSCLE; MICROTUBULE-ASSOCIATED PROTEIN-2; PHEROMONE RESPONSE PATHWAY; MITOGENIC AGENTS INDUCE; GROWTH-FACTOR; XENOPUS-OOCYTES; C-JUN; SACCHAROMYCES-CEREVISIAE AB The MAP kinases, discovered approximately 20 years ago, together with their immediate upstream regulators, are among the most highly studied signal transduction molecules. This body of work has shaped many aspects of our present views of signal transduction by protein kinases. The effort expended in this area reflects the extensive participation of these regulatory modules in the control of cell fate decisions, i.e., proliferation, differentiation and death, across all eukaryotic phylla and in all tissues of metazoans. The discovery of these kinases is reviewed, followed by a discussion of some of the features of this signaling module that account for its broad impact on cell function and its enormous interest to many investigators. (C) 2006 Elsevier B.V All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Avruch, J (reprint author), Harvard Univ, Sch Med, Dept Med, 185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NIDDK NIH HHS [R37 DK017776, R37 DK017776-32] NR 189 TC 121 Z9 131 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD AUG PY 2007 VL 1773 IS 8 BP 1150 EP 1160 DI 10.1016/j.bbamcr.2006.11.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 205AX UT WOS:000249086200002 PM 17229475 ER PT J AU Kumar, A Tyagi, NK Arevalo, E Miller, KW Kinne, RKH AF Kumar, Azad Tyagi, Navneet K. Arevalo, Enrique Miller, Keith W. Kinne, Rolf K. H. TI A proteomic study of sodium/D-glucose cotransporter 1 (SGLT1): Topology of loop 13 and coverage of other functionally important domains SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE sodium/D-glucose cotransporter 1; LC-MS/MS; membrane topology; D-glucose; phlorizin ID GLUCOSE COTRANSPORTER SGLT1; INTEGRAL MEMBRANE-PROTEIN; FLIGHT MASS-SPECTROMETRY; CHEMICAL CROSS-LINKING; NA+/GLUCOSE COTRANSPORTER; TRYPTOPHAN FLUORESCENCE; POSTTRANSLATIONAL MODIFICATIONS; CONFORMATIONAL-CHANGES; SUGAR-BINDING; PEPTIDE MAPS AB In order to obtain further information about the structure and function of human sodium/D-glucose cotransporter I (hSGLT l), the recombinant protein was subjected, either after reconstitution into liposomes or in its free form, to proteolysis followed by nanoscale microcapillary liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). The peptides released from SGLTl proteoliposomes by trypsin bead digestion represented the early N-terminal, loop 7, and loop 9, supporting topology models that place these domains on the extracellular side of the protein. Trypsin bead digestion generated, however, also a number of peptides derived from loop 13 whose topology with regard to the membrane is hitherto a point of debate. Sequence coverage was provided from amino acids 559 to 644, suggesting that loop 13 is almost completely accessible at the extravesicular face of the proteoliposomes. These results support the notion that major parts of loop 13, essential for the interaction with transport inhibitors in vivo, are located extracellularly in intact cells. In-gel trypsin, chymotrypsin, and in particular trypsin/ chymotrypsin digestion of recombinant SGLTl in combination with LC-MS/MS provide extensive sequence coverage of the protein, including domains involved in sugar and inhibitor binding and potential phosphorylation sites. These studies demonstrate that proteomic analysis combined with mass spectrometry is a useful tool to characterize regions of SGLTl that are important for its function and regulation. (c) 2007 Elsevier B.V. All rights reserved. C1 Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. RP Kinne, RKH (reprint author), Max Planck Inst Mol Physiol, Otto Hahn Str 11, D-44227 Dortmund, Germany. EM rolf.kinne@mpi-dortmund.mpg.de FU NIGMS NIH HHS [GM 58448] NR 48 TC 10 Z9 10 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD AUG PY 2007 VL 1774 IS 8 BP 968 EP 974 DI 10.1016/j.bbapap.2007.05.010 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 205XX UT WOS:000249149600002 PM 17588833 ER PT J AU Lepine, F Dekimpe, V Lesic, B Milot, S Lesimple, A Mamer, OA Rahme, LG Deziel, E AF Lepine, Francois Dekimpe, Valerie Lesic, Biliana Milot, Sylvain Lesimple, Alain Mamer, Orval A. Rahme, Laurence G. Deziel, Eric TI PqsA is required for the biosynthesis of 2,4-dihydroxyquinoline (DHQ), a newly identified metabolite produced by Pseudomonas aeruginosa and Burkholderia thailandensis SO BIOLOGICAL CHEMISTRY LA English DT Article DE 2,4-dihydroxyquinoline; 4-hydroxy-2-alkylquinolines; mass spectrometry; natural product; Pseudomonas aeruginosa; PqsA ID TO-CELL COMMUNICATION; QUINOLONE SIGNAL SYNTHESIS; QUORUM-SENSING CIRCUITRY; VIRULENCE; GENES; MVFR; PATHOGENESIS; EXPRESSION; KYNURENINE; BACTERIA AB A new metabolite, 2,4-dihydroxyquinoline (DHQ), was identified in cultures of the bacteria Pseudomonas aeruginosa and Burkholderia thailandensis. We found that the biosynthesis of DHQ correlates with the presence of a functional PqsA, which is a product of the pqsABCDE operon responsible for the synthesis of 4-hydroxy-2alkylquinolines (HAQs) in P. aeruginosa. However, DHQ is not a degradation product or precursor of HAQs. This finding sheds some light on the poorly understood biosynthesis pathway of HAQs, which includes important communication signals regulating the expression of virulence factors. C1 INRS, Inst Armand Frappier, Laval, PQ H7V 1B7, Canada. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA 02114 USA. McGill Univ, McGill Biomed Mass Spectrometry Unit, Montreal, PQ H3A 1A4, Canada. RP Lepine, F (reprint author), INRS, Inst Armand Frappier, Laval, PQ H7V 1B7, Canada. EM francois.lepine@iaf.inrs.ca RI Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 FU Canadian Institutes of Health Research [77642]; NIAID NIH HHS [R01 AI063433, R01AI063433] NR 27 TC 19 Z9 19 U1 1 U2 10 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD AUG PY 2007 VL 388 IS 8 BP 839 EP 845 DI 10.1515/BC.2007.100 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 197GH UT WOS:000248542100010 PM 17655503 ER PT J AU Hazlett, EA Speiser, LJ Goodman, M Roy, M Carrizal, M Wynn, JK Williams, WC Romero, M Minzenberg, MJ Siever, LJ New, AS AF Hazlett, Erin A. Speiser, Lisa J. Goodman, Marianne Roy, Marcela Carrizal, Michael Wynn, Jonathan K. Williams, William C. Romero, Michelle Minzenberg, Michael J. Siever, Larry J. New, Antonia S. TI Exaggerated affect-modulated startle during unpleasant stimuli in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE affective startle; borderline personality disorder; emotion; startle eyeblink ID BLINK MODULATION; EMOTION; REFLEX; ANXIETY; PSYCHOPATHY; SCHIZOTYPAL; DEPRESSION; REACTIVITY; MEN AB Background: Excessive emotional responding is considered to be a hallmark of borderline personality disorder (BPD). The affect-modulated startle response is a reliable indicator of emotional processing of stimuli. The aim of this study was to examine emotional processing in BPD patients (n = 27) and healthy control subjects (n = 21). Methods: Participants viewed an intermixed series of unpleasant, borderline-salient (e.g., "hate"), and neutral (e.g., "view") words and were instructed to think about the meaning of the word for them personally while eyeblink responses were assessed. Results: The BPD patients exhibited larger startle eyeblink during unpleasant but not neutral words, indicating exaggerated physiological affect. This finding remained significant when we controlled for comorbid diagnoses, including generalized anxiety disorder and posttraumatic stress disorder. Greater symptom severity was associated with greater affective-startle difference scores (unpleasant-neutral). Conclusions: Consistent with the symptom of affective clysregulation, these results suggest an abnormality in the processing of unpleasant emotional stimuli by BPD patients. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, New York, NY USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Educ & Clin Ctr, Los Angeles, CA USA. Eastern Washington Univ, Dept Psychol, Cheney, WA 99004 USA. RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. EM erin.hazlett@mssm.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH073911] NR 42 TC 41 Z9 42 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2007 VL 62 IS 3 BP 250 EP 255 DI 10.1016/j.biopsych.2006.10.028 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 192NF UT WOS:000248208100009 PM 17258691 ER PT J AU Ito, T Yeo, Y Highley, CB Bellas, E Kohane, DS AF Ito, Taichi Yeo, Yoon Highley, Christopher B. Bellas, Evangelia Kohane, Daniel S. TI Dextran-based in situ cross-linked injectable hydrogels to prevent peritoneal adhesions SO BIOMATERIALS LA English DT Article DE post-operative adhesion; dextran; carboxymethyl dextran; carboxymethyl cellulose; In situ cross-linking hydrogel; rabbit sidewall defectcecum abrasion model ID POSTOPERATIVE ABDOMINAL ADHESIONS; HYALURONIC-ACID; FUNCTIONALIZED DERIVATIVES; SURGERY; SAFETY AB Peritoneal adhesions are serious sequelae of surgery, and can cause significant morbidity and/or mortality due to pain, infertility, and bowel obstruction. We have designed and synthesized novel dextran (DX)-based injectable hydrogels for adhesion prevention, which are formed by mixing hydrazide-modified carboxymethyldextran (CMDX ADH) with aldehyde-modified DX (DX-CHO) or carboxymethylcellulose (CMC-CHO). At high polymer concentrations, hydrogels formed very quickly upon mixing, e.g. 5% CMDX ADH with 6% DX-CHO (= CMDX-DX; 1.8 s) and 5% CMDX-ADH with 6% CMC-CHO (= CMDX-CMC; 5.8 s). CMDX-DX shrank after gelling, while CMDX-CMC swelled. CMDX-ADH and CMC-CHO showed minimal to mild cytotoxicity to mesothelial cells and macrophages in vitro, while DX-CHO was very cytotoxic. However, all cross-linked gels had very mild cytotoxicity. When applied in a rabbit sidewall defect-bowel abrasion model of adhesion formation, CMDX-CMC greatly reduced the formation of adhesions while CMDX DX worsened them. (c) 2007 Elsevier Ltd. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Biomat & Drug Delivery, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pediat Intens care, Boston, MA 02114 USA. RP Kohane, DS (reprint author), Tokyo Inst Technol, Chem Resources Lab, Midori Ku, R1-17,4259 Nagastuta, Yokohama, Kanagawa 2268503, Japan. EM dkohane@partners.org FU NIGMS NIH HHS [GM073626] NR 27 TC 72 Z9 75 U1 5 U2 54 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD AUG PY 2007 VL 28 IS 23 BP 3418 EP 3426 DI 10.1016/j.biomaterials.2007.04.017 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 180KT UT WOS:000247362700006 PM 17470376 ER PT J AU von Knoch, F Eckhardt, C Alabre, CI Schneider, E Rubash, HE Shanbhag, AS AF von Knoch, Fabian Eckhardt, Christina Alabre, Claude I. Schneider, Erich Rubash, Harry E. Shanbhag, Arun S. TI Anabolic effects of bisphosphonates on peri-implant bone stock SO BIOMATERIALS LA English DT Article DE bisphosphonates; alendronate; zoledronate; total joint replacements; wear debris; UHMWPE ID PARTICLE-INDUCED OSTEOLYSIS; TOTAL HIP-ARTHROPLASTY; ZOLEDRONIC ACID; WEAR DEBRIS; OSTEOBLASTIC PHENOTYPE; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; POROUS IMPLANTS; STROMAL CELLS; IN-VITRO AB The long-term durability of total joint replacements is critically dependent on adequate peri-implant bone stock, which can be compromised by wear debris-mediated osteolysis. This study investigated the effects of bisphosphonates on enhancing peri-implant bone in the presence of clinically relevant ultra-high molecular weight polyethylene (UHMWPE) wear debris. Fiber-mesh coated titanium-alloy plugs were implanted bilaterally in the femoral condyles of 36 New Zealand white rabbits. Implants in the left femora were covered With submicron UHMWPE particles during surgery. Rabbits were administered either no drug, subcutaneous alendronate weekly (1.0mg/kg/week) or a single dose of intravenous zoledronate (0.015 mg/kg). A total of 6/12 rabbits in each group were sacrificed Lit 6 weeks and the remainder at 12 weeks postoperatively. Peri-implant bone stock was analyzed radiographically and histomorphometrically. Radiographically. both bisphosphonates significantly increased periprosthetic cortical thickness at 6 weeks (p < 0.0001; alendronate: + 18%: zoledronate: + 11%) and at 12 weeks (p = 0.001; alendronate: + 17% zoledronate: + 19%). Histomorphometrically. alendronate and zoledronate raised peri-implant bone volume (BV/TV) up to 2-fold after 6 weeks without added wear debris and more than 3-fold when wear debris was present. Furthermore a 6-week bisphosphonate treatment increased osteoid thickness in the absence of wear debris (alendronate: + 132% p = 0.007; zoledronate: + 67% p = 0.51) and in the presence of wear debris (alendronate: + 134%, P = 0.023: zoledronate: + 138%. p = 0.016). In summary, alendronate and zoledronate treatment increased periprosthetic bone stock in a rabbit femoral model. particularly in the presence of UHMWPE wear debris. These new findings suggest that bisphosphonates may more than compensate for the well-documented negative effects of wear debris on peri-implant bone stock. The combined antiresorptive and osteoanabolic effects of bisphosphonates on periprosthetic bone stock may have an important role for critically improving the biological fixation and ultimate durability of total joint arthroplasty. (c) 2007 Published by Elsevier Ltd. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Schulthess Clin, Dept Orthopaed Surg, Zurich, Switzerland. AO Res Inst, Davos, Switzerland. RP Shanbhag, AS (reprint author), GRJ 1115,55 Fruit St, Boston, MA 02114 USA. EM shanbhag@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR-47465-02] NR 50 TC 17 Z9 18 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD AUG PY 2007 VL 28 IS 24 BP 3549 EP 3559 DI 10.1016/j.biomaterials.2007.04.024 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 189BB UT WOS:000247962300009 PM 17498799 ER PT J AU Akkin, T Joo, C de Boer, JF AF Akkin, Taner Joo, Chulmin de Boer, Johannes F. TI Depth-resolved measurement of transient structural changes during action potential propagation SO BIOPHYSICAL JOURNAL LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; BIREFRINGENCE CHANGES; RETINAL PHYSIOLOGY; SCATTERING CHANGES; PHASE MICROSCOPY; LIGHT SCATTERING; NEURAL ACTIVITY; NERVE; INTERFEROMETER AB We report noncontact optical measurement of fast transient structural changes in the crustacean nerve during action potential propagation without the need for exogenous chemicals or reflection coatings. The technique, spectral domain optical coherence tomography, provides real- time cross- sectional images of the nerve with micron- scale resolution to select a specific region for functional assessment and interferometric phase sensitivity for subnanometer- scale motion detection. Noncontact optical measurements demonstrate nanometer- scale transient movement on a 1- ms timescale associated with action potential propagation in crayfish and lobster nerves. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP de Boer, JF (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976 FU NCRR NIH HHS [R01 RR019768, R01-RR19768]; NEI NIH HHS [R01 EY014975, R01-EY014975] NR 33 TC 32 Z9 32 U1 1 U2 13 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2007 VL 93 IS 4 BP 1347 EP 1353 DI 10.1529/biophysj.106.091298 PG 7 WC Biophysics SC Biophysics GA 192NM UT WOS:000248208800028 PM 17526590 ER PT J AU Richards, WG Van Oss, SB Glickman, JN Chirieac, LR Yeap, B Dong, L Gordon, GJ Mercer, H Gill, KK Imrich, A Bueno, R Sugarbaker, DJ AF Richards, W. G. Van Oss, S. B. Glickman, J. N. Chirieac, L. R. Yeap, B. Dong, L. Gordon, G. J. Mercer, H. Gill, K. K. Imrich, A. Bueno, R. Sugarbaker, D. J. TI A microaliquoting technique for precise histological annotation and optimization of cell content in frozen tissue specimens SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 01-05, 2006 CL Washington, DC SP Amer Assoc Canc Res DE cancer; frozen tissue; mesothelioma; microaliquots; RNA preparation; tissue banking ID GENE-EXPRESSION SIGNATURES; MOLECULAR CLASSIFICATION; GASTRIC-CANCER; LUNG; MESOTHELIOMA; RNA; CARCINOMAS; MICRODISSECTION; TAMOXIFEN; FIXATION AB Knowledge of the exact cell content of frozen tissue samples is of growing importance in genomic research. We developed a microaliquoting technique to measure and optimize the cell composition of frozen tumor specimens for molecular studies. Frozen samples of 31 mesothelioma cases were cut in alternating thin and thick sections. Thin sections were stained and evaluated visually. Thick sections, i.e., microaliquots, were annotated using bordering stained sections. A range of cellular heterogeneity was observed among and within samples. Precise annotation of samples was obtained by integration and compared to conventional single face and "front and back" section estimates of cell content. Front and back estimates were more highly correlated with block annotation by microaliquoting than were single face estimates. Both methods yielded discrepant estimates, however, and for some studies may not adequately account for the heterogeneity of mesothelioma or other malignancies with variable cellular composition. High yield and quality RNA was extracted from precision annotated, tumor enriched subsamples prepared by combining individual microaliquots with the highest tumor cellularity estimates. Microaliquoting provides accurate cell content annotation and permits genomic analysis of enriched subpopulations of cells without fixation or amplification. C1 [Richards, W. G.; Van Oss, S. B.; Dong, L.; Gordon, G. J.; Mercer, H.; Gill, K. K.; Bueno, R.; Sugarbaker, D. J.] Brigham & Womens Hosp, Div Theoret Surg, Boston, MA 02115 USA. [Glickman, J. N.; Chirieac, L. R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, B.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Imrich, A.] Harvard Univ, Sch Publ Hlth, Dept Pathol, Boston, MA 02115 USA. RP Richards, WG (reprint author), Brigham & Womens Hosp, Div Theoret Surg, 75 Francis St, Boston, MA 02115 USA. EM wrichards@partners.org NR 27 TC 3 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE-TAYLOR & FRANCIS PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON, OXFORSHIRE OX14 4RN, ENGLAND SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD AUG-OCT PY 2007 VL 82 IS 4-5 BP 189 EP 197 DI 10.1080/10520290701488121 PG 9 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 252ZV UT WOS:000252487700002 PM 17917854 ER PT J AU Pomerantz, MM Freedman, ML Kantoff, PW AF Pomerantz, Mark M. Freedman, Matthew L. Kantoff, Philip W. TI Genetic determinants of prostate cancer risk SO BJU INTERNATIONAL LA English DT Editorial Material DE prostate cancer risk; genetics; association studies; chromosome 8 ID CHROMOSOME 8Q24; VARIANT; TWINS C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. MIT, Cambridge, MA USA. RP Pomerantz, MM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. EM mpomerantz@partners.org NR 15 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD AUG PY 2007 VL 100 IS 2 BP 241 EP 243 DI 10.1111/j.1464-410X.2007.06996 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 186VB UT WOS:000247805400002 PM 17542988 ER PT J AU Lee, AK D'Amico, AV AF Lee, Andrew K. D'Amico, Anthony V. TI Using prostate-specific antigen doubling time in clinical practice SO BJU INTERNATIONAL LA English DT Editorial Material DE prostate cancer; prostate specific antigen; PSA doubling time; PSA velocity ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; BIOCHEMICAL RECURRENCE; PROGRESSION; POINT C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, AK (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM aklee@mdanderson.org NR 12 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD AUG PY 2007 VL 100 IS 2 BP 243 EP 244 DI 10.1111/j.1464-410X.2007.06997.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 186VB UT WOS:000247805400003 PM 17511769 ER PT J AU Liu, GM Daneshgari, F Li, M Lin, DL Lee, U Li, TS Damaser, MS AF Liu, Guiming Daneshgari, Firouz Li, Mei Lin, Danli Lee, Una Li, Tiansen Damaser, Margot S. TI Bladder and urethral function in pelvic organ prolapsed lysyl oxidase like-1 knockout mice SO BJU INTERNATIONAL LA English DT Article DE urinary incontinence; pelvic organ prolapse; elastin; lysyl oxidase like-1; mice ID FEMALE RAT AB To examine bladder and urethral function in pelvic organ prolapsed lysyl oxidase like-1 (LOXL1) knockout mice. MATERIALS AND METHODS Female parous Loxl1(-/-) mice in the stable phase of prolapse, and age-matched wild type (WT) mice (six each) had conscious cystometry, leak-point pressure (LPP) testing, and contractile responses assessed of their bladder muscle strips to KCl, electrical-field stimulation, ATP, and carbachol. C1 Cleveland Clin, Glickman Urol Inst, Cleveland, OH 44195 USA. Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA. Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Daneshgari, F (reprint author), Cleveland Clin, Glickman Urol Inst, 9500 Euclid Ave,ND20, Cleveland, OH 44195 USA. EM daneshf@ccf.org FU NIDDK NIH HHS [KO8 DK02631, DK61018-02S1, U01 DK-076162] NR 14 TC 15 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD AUG PY 2007 VL 100 IS 2 BP 414 EP 418 DI 10.1111/j.1464-410X.2007.06929.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 186VB UT WOS:000247805400039 PM 17555473 ER PT J AU Enzler, T Gillessen, S Dougan, M Allison, JP Neuberg, D Oble, DA Mihm, M Dranoff, G AF Enzler, Thomas Gillessen, Silke Dougan, Michael Allison, James P. Neuberg, Donna Oble, Darryl A. Mihm, Martin Dranoff, Glenn TI Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of beta cells SO BLOOD LA English DT Article ID NONOBESE DIABETIC MICE; DENDRITIC CELLS; NOD MICE; T-CELLS; APOPTOTIC CELLS; GM-CSF; AUTOIMMUNE INFLAMMATION; ANTITUMOR IMMUNITY; STAT5 DYSFUNCTION; IN-VIVO AB The pathogenesis of type 1 diabetes (T1D) involves the immune-mediated destruction of insulin-producing p cells in the pancreatic islets of Langerhans. Genetic analysis of families with a high incidence of T1D and nonobese diabetic (NOD) mice, a prototypical model of the disorder, uncovered multiple susceptibility loci, although most of the underlying immune defects remain to be delineated. Here we report that aged mice doubly deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) manifest insulitis, destruction of insulin-producing 0 cells, and compromised glucose homeostasis. Macrophages from mutant mice produce increased levels of p40 after LPS stimulation, whereas concurrent ablation of interferon-gamma (IFN-gamma) ameliorates the disease. The administration of antibodies that block cytotoxic T lymphocyte associated antigen-4 (CTLA-4) to young mutant mice precipitates the onset of insulitis and hyperglycemia. These results, together with previous reports of impaired hematopoietic responses to GM-CSF and IL-3 in patients with T1D and in NOD mice, indicate that functional deficiencies of these cytokines contribute to diabetes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, New York, NY USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 64 TC 17 Z9 17 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 AUG 1 PY 2007 VL 110 IS 3 BP 954 EP 961 DI 10.1182/blood-2006-08-043786 PG 8 WC Hematology SC Hematology GA 196WW UT WOS:000248514700032 PM 17483299 ER PT J AU Shtatland, T Guettler, D Kossodo, M Pivovarov, M Weissleder, R AF Shtatland, Timur Guettler, Daniel Kossodo, Misha Pivovarov, Misha Weissleder, Ralph TI PepBank - a database of peptides based on sequence text mining and public peptide data sources SO BMC BIOINFORMATICS LA English DT Article ID PHAGE DISPLAY LIBRARY; PROTEIN INTERACTIONS; BINDING PEPTIDES; CURATED DATABASE; MHC-BINDING; INFORMATION; NOMENCLATURE; RESOURCE; GROWTH; CLASSIFICATION AB Background: Peptides are important molecules with diverse biological functions and biomedical uses. To date, there does not exist a single, searchable archive for peptide sequences or associated biological data. Rather, peptide sequences still have to be mined from abstracts and full-length articles, and/or obtained from the fragmented public sources. Description: We have constructed a new database (PepBank), which at the time of writing contains a total of 19,792 individual peptide entries. The database has a web-based user interface with a simple, Google-like search function, advanced text search, and BLAST and Smith-Waterman search capabilities. The major source of peptide sequence data comes from text mining of MEDLINE abstracts. Another component of the database is the peptide sequence data from public sources (ASPD and UniProt). An additional, smaller part of the database is manually curated from sets of full text articles and text mining results. We show the utility of the database in different examples of affinity ligand discovery. Conclusion: We have created and maintain a database of peptide sequences. The database has biological and medical applications, for example, to predict the binding partners of biologically interesting peptides, to develop peptide based therapeutic or diagnostic agents, or to predict molecular targets or binding specificities of peptides resulting from phage display selection. The database is freely available on http://pepbank.mgh.harvard.edu/, and the text mining source code (Peptide:: Pubmed) is freely available above as well as on CPAN (http://www.cpan.org/). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. No Essex Community Coll, Haverhill, MA 01830 USA. RP Shtatland, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,139 St,Room 5406, Charlestown, MA 02129 USA. EM tshtatland@partners.org; dguettler@partners.org; dalten@gmail.com; mpivovarov@partners.org; weissleder@helix.mgh.harvard.edu RI Kossodo, Mischa/B-2338-2013 FU NCI NIH HHS [P50 CA086355, P50-CA86355, U54 CA126515, U54-CA126515]; NIAID NIH HHS [P01 AI054904, P01-AI54904] NR 68 TC 66 Z9 67 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD AUG 1 PY 2007 VL 8 AR 280 DI 10.1186/1471-2105-8-280 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 209PE UT WOS:000249399700001 PM 17678535 ER PT J AU Saito, AM Zahrieh, D Cutler, C Ho, VT Antin, JH Soiffer, RJ Alyea, EP Lee, SJ AF Saito, A. M. Zahrieh, D. Cutler, C. Ho, V. T. Antin, J. H. Soiffer, R. J. Alyea, E. P. Lee, S. J. TI Lower costs associated with hematopoietic cell transplantation using reduced intensity vs high-dose regimens for hematological malignancy SO BONE MARROW TRANSPLANTATION LA English DT Article DE hematopoietic cell transplantation; cost; outcomes research ID BONE-MARROW-TRANSPLANTATION; PREPARATIVE REGIMENS; MORTALITY; THERAPY; GRAFT; RISK; COMPLICATIONS; REQUIREMENTS; ENGRAFTMENT; CHIMERISM AB We compared inpatient and outpatient costs alongside clinical outcomes associated with hematopoietic cell transplantation between 2000 and 2003 with high-dose regimens (HDCT, n = 185) and with reduced intensity regimens (RICT, n = 90) from human leukocyte antigen (HLA)-matched donors for patients with hematological malignancies. With a comparable median follow-up of 3 years, long-term clinical outcomes, including cumulative incidence of chronic graft-vs-host disease, disease-free survival and overall survival, were similar between the two groups. In the univariate analysis, median costs for the first 100 days ($104 380 vs $42 149) and 1 year ($128 253 vs $80 499) in the HDCT group were higher than those in the RICT group. Median days of hospitalization are also higher for HDCT recipients (39 vs 21), although the number of outpatient clinic visits for HDCT recipients were fewer compared to that for RICT recipients (16 vs 25) during the first year. Adjusting for patient characteristics, RICT recipients had approximately 16 fewer days of hospitalization and cost $53 030 less than HDCT recipients within the first year after transplantation. Our data suggest that substantially lower costs and fewer days of hospitalization within the first year after RICT procedures can be obtained with no compromise of longterm clinical outcomes compared to HDCT procedures. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Saito, AM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Med Oncol, 44 Binney St,SM 275, Boston, MA 02115 USA. EM akiko_saito@dfci.harvard.edu NR 40 TC 22 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2007 VL 40 IS 3 BP 209 EP 217 DI 10.1038/sj.bmt.1705733 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 191ZF UT WOS:000248169800004 PM 17563734 ER PT J AU Chow, BJW Dennie, C Hoffmann, U So, D Dekemp, RA Ruddy, TD Beanlands, RS AF Chow, Benjamin J. W. Dennie, Carole Hoffmann, Udo So, Derek Dekemp, Robert A. Ruddy, Terrence D. Beanlands, Rob S. TI Comparison of computed tomographic angiography versus rubidium-82 positron emission tomography for the detection of patients with anatomical coronary artery disease SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article DE computed tomographic coronary angiography; coronary artery disease; diagnosis; Positron emission tomography ID MS TEMPORAL RESOLUTION; DIAGNOSTIC-ACCURACY; PROGNOSTIC VALUE; IMAGE QUALITY; NONINVASIVE DETECTION; DIPYRIDAMOLE STRESS; MULTIDETECTOR CT; STENOSES; LESIONS; SUBMILLIMETER AB BACKGROUND: The present study compared computed tomographic Coronary angiography (CTA) and positron emission tomography (PET) for the detection of significant anatomical coronary artery stenosis as defined by conventional invasive Coronary angiography (CICA). METHODS: The Study protocol was approved by the local ethics board, and informed consent was obtained from all patients. Of the 26 patients (mean age 57 +/- 9 years, 18 men) who prospectively underwent CTA and rubidium-82 PET before CICA, 24 patients had a history of chest pain. Images were interpreted by expert readers and assessed for the presence of anatomically significant coronary stenosis (50% luminal diameter stenosis or greater) or myocardial perfusion defects. Diagnostic test characteristics were analyzed Using patient-based, territory based, vessel-based and segment-based analyses. RESULTS: In the 24 patients referred for chest pain, CTA hall similar sensitivity to PET but was more specific (sensitivity 95% [95% CI 72% to 100%] Versus 95% (95% Cl 72% to 100%], respectively; specificity 100% [95% CI 46% to 100%] versus 60% [95% CI 17% to 93%], respectively) in the detection of patients with anatomical coronary artery stenosis of 50% or greater. On a per-segment basis of all 26 patients, CTA had a sensitivity, specificity, positive predictive value and negative predictive Value of 72%, 99%, 91% and 95%, respectively, in all coronary segments. CONCLUSIONS: Coronary CTA has a similar sensitivity and specificity to rubidium-82 PET for the identification of patients with significant anatomical coronary artery disease. C1 Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON K1Y 4W7, Canada. Dept Radiol, Ottawa, ON, Canada. Ottawa Hosp, Div Nucl Med, Ottawa, ON, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Sch Publ Hlth, Boston, MA USA. RP Chow, BJW (reprint author), Univ Ottawa, Inst Heart, Div Cardiol, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM bchow@ottawaheort.ca NR 51 TC 11 Z9 11 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD AUG PY 2007 VL 23 IS 10 BP 801 EP 807 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201KD UT WOS:000248829200007 PM 17703259 ER PT J AU Zhu, AX Stuart, K Blaszkowsky, LS Muzikansky, A Reitberg, DP Clark, JW Enzinger, PC Bhargava, P Meyerhardt, JA Horgan, K Fuchs, CS Ryan, DP AF Zhu, Andrew X. Stuart, Keith Blaszkowsky, Lawrence S. Muzikansky, Alona Reitberg, Donald P. Clark, Jeffrey W. Enzinger, Peter C. Bhargava, Pankaj Meyerhardt, Jeffrey A. Horgan, Kerry Fuchs, Charles S. Ryan, David P. TI Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma SO CANCER LA English DT Article DE hepatocellular carcinoma; cetuximab; epidermal growth factor receptor inhibition; pharmacokinetics; clinical trial ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; FACTOR RECEPTOR BLOCKADE; FACTOR-ALPHA; II TRIAL; COLORECTAL-CANCER; EXPRESSION; COMBINATION; THERAPY; ANTAGONISTS AB Background. Epidermal growth factor receptor (EGFR) and ligand expression is frequently seen in hepatocellular carcinoma (HCC). A phase 2 study was performed with cetuximab, a chimeric monoclonal antibody that binds specifically to EGFR, in patients with advanced HCC. Methods. Eligibility criteria included unresectable or metastatic measurable HCC, an Eastern Cooperative Oncology Group performance status <= 2, Cancer of the Liver Italian Program (CLIP) score <= 3, and adequate organ functions. The initial dose of cetuximab was 400 mg/m(2) given intravenously followed by weekly intravenous infusions at 250 mg/m(2). Each cycle was defined as 6 consecutive weekly treatments. EGFR expression was assayed by immunohistochemistry and trough serum concentrations of cetuximab were determined during the first cycle. Results. Thirty patients were enrolled and assessable for efficacy and toxicity. No responses were seen. Five patients had stable disease (median time, 4.2 months; range, 2.8-4.2 months). The median overall survival was 9.6 months (95% confidence interval [CI), 4.3-12.1 months) and the median progression-free survival (PFS) was 1.4 months (95% CI, 1.2-2.6 months). The treatment was generally well tolerated. No treatment- related grade 4-5 toxicities occurred. Grade 3 (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [version 3.0]) aspartate amino transferase, hypomagnesemia, and fever without neutropenia were noted in I patient (3.3%) each. On Week 6 of Cycle 1, arithmetic mean serum cetuximab concentrations for patients with Child-Turcotte- Pugh (CTP) A and CTP B disease were 47.6 mcg/mL and 66.9 mcg/mL, respectively. Conclusions. Although cetuximab could be safely administered with tolerable toxicity profiles, it demonstrated no antitumor activity in HCC in this phase 2 study. Cetuximab trough concentrations were not notably altered in patients with mild to moderate hepatic dysfunction. C1 Massachusetts Gen Hosp, Tucker Gosnell Ctr Gastrointestinal Canc, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Tucker Gosnell Ctr Gastrointestinal Canc, Ctr Canc, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM azhu@partners.org NR 35 TC 151 Z9 166 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2007 VL 110 IS 3 BP 581 EP 589 DI 10.1002/cncr.22829 PG 9 WC Oncology SC Oncology GA 192MR UT WOS:000248206700014 PM 17583545 ER PT J AU Livestro, DP Kaine, EM Michaelson, JS Mihm, MC Haluska, FG Muzikansky, A Sober, AJ Tanabe, KK AF Livestro, Daan P. Kaine, Emily M. Michaelson, James S. Mihm, Martin C. Haluska, Frank G. Muzikansky, Alona Sober, Arthur J. Tanabe, Kenneth K. TI Melanoma in the young: Differences and similarities with adult melanoma - A case-matched controlled analysis SO CANCER LA English DT Article DE pediatric; melanoma; sentinel lymph node; survival ID CUTANEOUS MALIGNANT-MELANOMA; LYMPH-NODE BIOPSY; CHILDHOOD MELANOMA; PEDIATRIC MELANOMA; CHILDREN; SURVIVAL; ADOLESCENTS; POPULATION; MANAGEMENT; TUMORS AB Background. Melanoma in the first 2 decades of life is rare and is less well characterized than melanoma in adults. Previously published comparisons of melanoma of the young (age <= 20 years) and in adults have been biased by the observation that primary melanomas of the young are significantly thicker on average than adult melanomas. In this study, the use of an adult control group that was matched for tumor thickness adjusted for this bias and allowed for a comparison of the biology of pediatric melanoma and adult melanoma. Methods. The authors identified young patients with melanoma who were treated at their institution between 1971 and 2002, and matched each patient by thickness and year of diagnosis to 2 adult control patients with melanoma. The study group of 73 young patients with melanoma (aged <= 20 years) was compared with to 146 adult case-matched control patients for clinical presentation, treatment, and clinically relevant outcome parameters, including disease-free and cause-specific survival. A subset of pediatric patients aged <= 13 years also was analyzed against case-matched adult controls. Results. The demographics and clinical presentation of the 2 groups were similar. Of the young patients with melanoma who underwent pathologic staging of clinically negative lymph nodes by either elective lymph node dissection or lymphatic mapping/ sentinel lymph node biopsy, 11 of 25 patients (44%) had positive lymph nodes compared with 11 of 46 patients (23.9%) among the adults. The overall incidence of positive lymph nodes was 17.8% in young melanoma patients and 9.6% in thickness- matched adult control patients. Nonetheless, 10-year cause-specific survival was similar between young melanoma patients and adult melanoma patients (89.4% and 79.3%, respectively). No significant differences were observed comparing young patients with melanoma aged < 13 years versus age > 13 years. Conclusions. Melanoma of the young had some important differences and similarities relative to adult melanoma. Lymph node metastases were more prevalent in young patients with melanoma compared with adult (thickness-matched) control patients; however, the 5- and 10-year survival rates were similar. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM ktanabe@partners.org NR 31 TC 69 Z9 70 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2007 VL 110 IS 3 BP 614 EP 624 DI 10.1002/cncr.22818 PG 11 WC Oncology SC Oncology GA 192MR UT WOS:000248206700018 PM 17577228 ER PT J AU Ashley, AC Sargent, DJ Alberts, SR Grothey, A Campbell, ME Morton, RF Fuchs, CS Ramanathan, RK Williamson, SK Findlay, BP Pitot, HC Goldberg, RM AF Ashley, Amanda C. Sargent, Daniel J. Alberts, Steven R. Grothey, Axel Campbell, Megan E. Morton, Roscoe F. Fuchs, Charles S. Ramanathan, Ramesh K. Williamson, Stephen K. Findlay, Brian P. Pitot, Henry C. Goldberg, Richard M. TI Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) - Intergroup trial N9741 in first-line treatment of metastatic colorectal cancer SO CANCER LA English DT Article DE metastatic colorectal cancer; chemotherapy; irinotecan; oxaliplatin; clinical trial ID PHASE-II TRIAL; ELDERLY-PATIENTS; POOLED ANALYSIS; CHEMOTHERAPY; COMBINATION; MULTICENTER; CPT-11 AB Background. Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741. Methods. This IROX regimen was oxaliplatin 85 mg/m(2) and irinotecan 200 mg/ in 2 administered every 3 weeks. The relation between adverse events on IROX to selected characteristics was analyzed. Time to progression (TTP), response rate, and overall survival for patients treated with IROX compared with patients treated with oxaliplatin with 5- fluorouracil (FOLFOX) were updated in this article. Results. Grade >= 3 gastrointestinal and hematologic toxicities were common with 39% patients experiencing neutropenia, 28% diarrhea, and 21% vomiting. Patients ages > 70 years experienced higher rates of grade >= 3 toxicity, with significantly higher rates of grade >= 3 hematologic toxicities (P =.02). Long-term toxicity was uncommon, and nearly all cases of grade >= 3 neurotoxicity resolved within 10 months. Fifty-two percent of patients required dose reductions for adverse events, and 26% experienced 119 hospitalizations related to complications of treatment or their disease, with 5 treatment -related deaths. This analysis confirmed prior findings that FOLFOX is superior to IROX in terms of response rate (43% vs 36%, p = 0.002), TTP (9.2 months vs 6.7 months, P <.0001), and overall survival (19.5 months vs 17.3 months, P =.0001). Conclusions. IROX was found to be less active than FOLFOX but with a similar toxicity profile except in patients ages >70 years. Although IROX may be considered in patients intolerant of 5-FU or in patients known to have a dihydropyrimidine dehydrogenase (DPD) deficiency, it should be used with caution in older patients. C1 Mayo Clin & Mayo Fdn, Div Med Oncol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Canc Ctr Stat, Rochester, MN 55905 USA. Iowa Oncol Res Assoc CCOP, Des Moines, IA USA. Dana Farber Canc Ctr Inst, Dept Med Oncol, Boston, MA USA. Univ Pittsburgh, Ctr Canc, Div Hematol Oncol, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Div Hematol Oncol, Kansas City, KS 66103 USA. Natl Canc Inst Canada, St Catharines, ON, Canada. Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. RP Alberts, SR (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM alberts.steven@mayo.edu RI Goldberg , Richard/M-1311-2013; OI Sargent, Daniel/0000-0002-2684-4741 FU NCI NIH HHS [CA-37404, CA-21115, CA-25224, CA-32102, CA-35101, CA-35195, CA-38926] NR 18 TC 21 Z9 26 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2007 VL 110 IS 3 BP 670 EP 677 DI 10.1002/cncr.22831 PG 8 WC Oncology SC Oncology GA 192MR UT WOS:000248206700025 PM 17559146 ER PT J AU Di Vizio, D Sotgia, F Williams, TM Hassan, GS Capozza, F Frank, PG Pestell, RG Loda, M Freeman, MR Lisanti, MP AF Di Vizio, Dolores Sotgia, Federico Williams, Terence M. Hassan, Ghado S. Capozza, Franco Frank, Philippe G. Pestell, Richard G. Loda, Massimo Freeman, Michael R. Lisanti, Michael P. TI Caveolin-1 is required for the upregulation of fatty acid synthase (FASN), a tumor promoter, during prostate cancer progression SO CANCER BIOLOGY & THERAPY LA English DT Article DE caveolin; fatty acid synthase; prostate cancer; biomarkers; tumor progression; metastasis; FASN ID HUMAN BREAST-CANCER; MAMMARY EPITHELIAL-CELLS; PATHOLOGICAL STAGE; GENETIC ABLATION; PLASMA-MEMBRANE; NULL MICE; EXPRESSION; OVEREXPRESSION; INHIBITION; CARCINOMA AB Prostate cancer is the second leading cause of cancer-related deaths in men. Fatty acid synthase (FASN) is normally upregulated during human prostate cancer onset and metastatic progression and its expression positively correlates with the development of advanced metastatic disease. However, it remains unknown what molecular factor(s) control FASN expression. It has been hypothesized that FASN functions as a tumor promoter during prostate cancer progression in humans. Consistently, an established mouse of model of prostate cancer, termed TRAMP mice, also shows the progressive upregulation of FASN levels during prostate cancer development. Here, we examine the role of caveolin-1 (Cav-1) in regulating FASN expression during prostate cancer progression. For this purpose, we crossed Cav-1(-/-) null mice with TRAMP mice to generate TRAMP/Cav-1(+/+) and TRAMP/Cav-1(-/-) mice. Then, we assessed the expression of FASN in Cov-1(+/+) and Cav-1(-)/(-) prostate tumors by immuno-histochemistry and Western blot analysis. Interestingly, our results indicate that FASN fails to be upregulated in Cav-1(-/-) tumors. Importantly, the tumors examined were the same morphological grade, but Cav-1(-/-) tumors were dramatically smaller and did not metastasize efficiently. We conclude that Cav-1 expression is normally required for the upregulation of FASN during prostate cancer progression. These results also mechanistically explain why TRAMP/Cav-1(-/-) mice are dramatically resistant to the development of prostate tumors and lung metastases, as they lack the expression of the FASN tumor promoter. Thus, TRAMP/Cav-1(-/-) mice will provide a novel model system to elucidate the role of FASN in prostate tumor progression. In addition, our results provide the first molecular genetic evidence that Cav-1 functions upstream of FASN during prostate cancer progression. C1 [Sotgia, Federico; Williams, Terence M.; Hassan, Ghado S.; Capozza, Franco; Frank, Philippe G.; Pestell, Richard G.; Lisanti, Michael P.] Thomas Jefferson Univ, Program Mol Biol & Genet, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. [Sotgia, Federico; Williams, Terence M.; Hassan, Ghado S.; Capozza, Franco; Frank, Philippe G.; Pestell, Richard G.; Lisanti, Michael P.] Thomas Jefferson Univ, Program Mol Biol & Genet, Kimmel Canc Ctr, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. [Di Vizio, Dolores; Freeman, Michael R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Urol Dis Res Ctr, Boston, MA 02115 USA. [Sotgia, Federico] Univ Genoa, G Gaslini Pediat Inst, Muscular & Neurodegenerat Dis Unit, Genoa, Italy. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. RP Lisanti, MP (reprint author), Thomas Jefferson Univ, Program Mol Biol & Genet, Kimmel Canc Ctr, Dept Canc Biol, 233 S 10th St, Philadelphia, PA 19107 USA. EM Michael.Lisonti@jefferson.edu RI Lisanti, Michael/C-6866-2013; Williams, Terence/I-9614-2014; Frank, Philippe/A-3463-2011 OI Frank, Philippe/0000-0003-4857-5279 FU NCI NIH HHS [R01CA98779, R01CA80250, R01 CA112303, R01CA93596] NR 46 TC 18 Z9 18 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD AUG PY 2007 VL 6 IS 8 BP 1263 EP 1268 PG 6 WC Oncology SC Oncology GA 255OH UT WOS:000252666800030 PM 17786030 ER PT J AU Ince, TA Richardson, AL Bell, GW Saitoh, M Godar, S Karnoub, AE Iglehart, JD Weinberg, RA AF Ince, Tan A. Richardson, Andrea L. Bell, George W. Saitoh, Maki Godar, Samuel Karnoub, Antoine E. Iglehart, James D. Weinberg, Robert A. TI Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes SO CANCER CELL LA English DT Article ID LYMPH-NODE STATUS; STEM-CELLS; EPIGENETIC CHANGES; EXPRESSION DATA; CANCER; SENESCENCE; IMMORTALIZATION; MODELS; INACTIVATION; CARCINOMA AB We investigated the influence of normal cell phenotype on the neoplastic phenotype by comparing tumors derived from two different normal human mammary epithelial cell populations, one of which was isolated using a new culture medium. Transformation of these two cell populations with the same set of genetic elements yielded cells that formed tumor xenografts exhibiting major differences in histopathology, tumorigenicity, and metastatic behavior. While one cell type (HMECs) yielded squamous cell carcinomas, the other cell type (BPECs) yielded tumors closely resembling human breast adenocarcinomas. Transformed BPECs gave rise to lung metastases and were Up to 10(4)-fold more tumorigenic than transformed HMECs, which are nonmetastatic. Hence, the pre-existing differences between BPECs and HMECs strongly influence the phenotypes of their transformed derivatives. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Womens & Perinatal Pathol,Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu FU NCI NIH HHS [K08 CA092013] NR 45 TC 192 Z9 194 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2007 VL 12 IS 2 BP 160 EP 170 DI 10.1016/j.ccr.2007.06.013 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 200RQ UT WOS:000248780900010 PM 17692807 ER PT J AU Deng, J Carlson, N Takeyama, K Dal Cin, P Shipp, M Letai, A AF Deng, Jing Carlson, Nicole Takeyama, Kunihiko Dal Cin, Paola Shipp, Margaret Letai, Anthony TI BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents SO CANCER CELL LA English DT Article ID BCL-2 FAMILY-MEMBERS; CYTOCHROME-C RELEASE; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; PROTOTYPE CANCER THERAPEUTICS; B-CELL LYMPHOMA; BH3-ONLY PROTEINS; CHROMOSOMAL BREAKPOINT; ANTIAPOPTOTIC BCL-2; FOLLICULAR LYMPHOMA; INDUCE APOPTOSIS AB Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic blocks is necessary to rationally target them. Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defects in cancer cells and separate them into three main classes based on position in the apoptotic pathway. BH3 profiling identifies cells that require BCL-2 for survival and predicts sensitivity to the BCL-2 antagonist ABT-737. BCL-2 dependence correlates with high levels of proapoptotic BIM sequestered by BCL-2. Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU NCI NIH HHS [K08 CA10254] NR 53 TC 260 Z9 263 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2007 VL 12 IS 2 BP 171 EP 185 DI 10.1016/j.ccr.2007.07.001 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 200RQ UT WOS:000248780900011 PM 17692808 ER PT J AU Rajaraman, P Wang, SS Rothman, N Brown, MM Black, PM Fine, HA Loeffler, JS Selker, RG Shapiro, WR Chanock, SJ Inskip, PD AF Rajaraman, Preetha Wang, Sophia S. Rothman, Nathaniel Brown, Merideth M. Black, Peter M. Fine, Howard A. Loeffler, Jay S. Selker, Robert G. Shapiro, William R. Chanock, Stephen J. Inskip, Peter D. TI Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LI-FRAUMENI-SYNDROME; NON-HODGKIN-LYMPHOMA; BREAST-CANCER; HAPLOTYPE FREQUENCIES; LUNG-CANCER; MDM2 SNP309; ASSOCIATION; P53; SUSCEPTIBILITY; VARIANT AB Despite the potential importance of the cell cycle and apoptosis pathways in brain tumor etiology, little has been published regarding brain tumor risk associated with common gene variants in these pathways. Using data from a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n = 388), meningioma (n = 162), and acoustic neuroma (n = 73) with respect to 12 single nucleotide polymorphisms from 10 genes involved in apoptosis and cell cycle control: CASP8, CCND1, CCNH, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, PTEN, and TP53. We observed significantly decreased risk of meningioma with the CASP8 Ex14-271A > T variant [odds ratio (OR)(AT), 0.8; 95% confidence interval (95% CI), 0.5-1.2; ORAA, 0.5; 95% Cl, 0.3-0.9; P-trend = 0.03] and increased risk of meningioma with the CASP8 Ex13+51G < C variant (ORGC, 1.4; 95% CI, 0.9-2.1; ORCC, 3.6; 95% CI, 1.0-13.1; P-trend = 0.04). The CT haplotype of the two CASP8 polymorphisms was associated with significantly increased risk of meningioma (OR, 1.7; 95% CI, 1.1-2.6), but was not associated with risk of glioma or acoustic neuroma. The CCND1 Ex4-1G > A variant was associated with increased risk for glioma, and the Ex8+49T > C variant of CCNH was associated with increased risk of glioma and acoustic neuroma. The MDM2 Ex12+162A > G variant was associated with significantly reduced risk of glioma. Our results suggest that common variants in the CASP8, CCND1, CCNH, and MDM2 genes may influence brain tumor risk. Future research in this area should include more detailed coverage of genes in the apoptosis/cell cycle control pathways. 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. NCI, Pediat Oncol Branch, NIH, Dept Hlth Human SErv, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. RP Rajaraman, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth Human SErv, EPS Room 7085,6120 Execut Blvd, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov FU Intramural NIH HHS NR 37 TC 66 Z9 71 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2007 VL 16 IS 8 BP 1655 EP 1661 DI 10.1158/1055-9965.EPI-07-0314 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 199SI UT WOS:000248715100022 PM 17684142 ER PT J AU Treszezamsky, AD Kachnic, LA Feng, ZH Zhang, JR Tokadjian, C Powell, SN AF Treszezamsky, Alejandro D. Kachnic, Lisa A. Feng, Zhihui Zhang, Junran Tokadjian, Chake Powell, Simon N. TI BRCA1- and BRCA2-deficient cells are sensitive to etoposide-induced DNA double-strand breaks via topoisomerase II SO CANCER RESEARCH LA English DT Article ID HOMOLOGOUS RECOMBINATION; EMBRYONIC LETHALITY; BRCA1 MUTATION; CANCER; REPAIR; DEFICIENCY; RADIATION; CHEMOTHERAPY; CISPLATIN; AGENTS AB The function of BRCA1 and BRCA2 in DNA repair could affect the sensitivity of cells to cytotoxic agents, and would therefore be an important component of planning therapy for breast and ovarian cancers. Previously, both BRCA1- and BRCA2-deficient tumors were shown to be sensitive to mitomycin C, and the mechanism was presumed to be a defect in the repair of interstrand crosslinks by homologous recombination. Here, we show that both BRCA1 and BRCA2 determine the sensitivity to the cytotoxic drug, etoposide, using genetic complementation of BRCA-deficient cells. Etoposide is known to bind to topoisomerase II and prevent the resolution of the "cleavable complex," in which one DNA duplex is passed through a second duplex. The specificity of this BRCA-dependent sensitivity was confirmed by the use of aclarubicin, which is a catalytic inhibitor of topoisomerase II and prevents the formation of the cleavable complex. In the presence of aclarubicin, the differential sensitivity of BRCA-proficient and BRCA-deficient cells was lost. Thus, etoposide requires the presence of topoisomerase II to show specific sensitization in the absence of the function of BRCA1 or BRCA2. We conclude that homologous recombination is used in the repair of DNA damage caused by topoisomerase II poisons. Overall, these results suggest that etoposide is a potentially useful drug in the treatment of BRCA-deficient human cancers. C1 Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA USA. Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. RP Powell, SN (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, 4511 Forest Pk St, St Louis, MO 63108 USA. EM snpowell@radonc.wustl.edu NR 20 TC 63 Z9 69 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 AUG 1 PY 2007 VL 67 IS 15 BP 7078 EP 7081 DI 10.1158/0008-5472.CAN-07-0601 PG 4 WC Oncology SC Oncology GA 197BW UT WOS:000248529300006 PM 17671173 ER PT J AU Godin-Heymann, N Bryant, I Rivera, MN Ulkus, L Bell, DW Riese, DJ Settleman, J Haber, DA AF Godin-Heymann, Nadia Bryant, Ianthe Rivera, Miguel N. Ulkus, Lindsey Bell, Daphne W. Riese, David J. Settleman, Jeffrey Haber, Daniel A. TI Oncogenic activity of epidermal growth factor receptor kinase mutant alleles is enhanced by the T790M drug resistance mutation SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CELL LUNG-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; ABL GENE MUTATION; BCR-ABL; TYROSINE KINASE; CLINICAL RESISTANCE; IMATINIB RESISTANCE; SELECTIVE INHIBITOR; ACQUIRED-RESISTANCE AB Activating mutations in the epidermal growth factor receptor (EGFR) characterize a subset of non-small cell lung cancers (NSCLC) with extraordinary sensitivity to targeted tyrosine kinase inhibitors (TKI). A single secondary EGFR mutation, T790M, arising in cis with the primary activating mutation, confers acquired resistance to these drugs. However, the T790M mutation is also detected in the absence of drug selection, suggesting that it may provide a growth advantage. We show here that although T790M alone has only a modest effect on EGFR function, when combined with the characteristic activating mutations L838R or del746-750, it results in a dramatic enhancement of EGFR activity. The double mutants show potent ligand-independent receptor autophosphorylation associated with altered cellular phenotypes, soft agar colony formation, and tumorigenesis in nude mice. The significant gain-of-function properties of these double mutants may explain their initial presence before drug selection and their rapid selection as the single drug resistance mutation during therapy with gefitinib/erlotinib, and suggests that they may contribute to the adverse clinical course of TKI-resistant NSCLC. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Purdue Univ, Sch Pharm, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Res Ctr, W Lafayette, IN 47907 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA114209-02, P01 CA095281, P01 CA95281, R01 CA114209-01A2, R01 CA114209-03, R01 CA114209-04, R01 CA115830, R01 CA115830-02] NR 41 TC 80 Z9 81 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2007 VL 67 IS 15 BP 7319 EP 7326 DI 10.1158/0008-5472.CAN-06-4625 PG 8 WC Oncology SC Oncology GA 197BW UT WOS:000248529300034 PM 17671201 ER PT J AU Arwert, E Hingtgen, S Figueiredo, JL Bergquist, H Mahmood, U Weissleder, R Shah, K AF Arwert, Esther Hingtgen, Shawn Figueiredo, Jose-Luiz Bergquist, Henry Mahmood, Umar Weissleder, Ralph Shah, Khalid TI Visualizing the dynamics of EGFR activity and antiglioma therapies in vivo SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; GLIOBLASTOMA-MULTIFORME; CETUXIMAB IMC-C225; TUMOR-REGRESSION; GENE-EXPRESSION; TYROSINE KINASE; CELL-MIGRATION; GLIOMA-CELLS; BRAIN-TUMORS; S-TRAIL AB Many altered pathways in cancer cells depend on growth factor receptors. In primary malignant gliomas, the amplification/alteration of the epidermal growth factor receptor (EGFR) has been shown to play a significant role in enhancing glioma burden. In an effort to dissect the role of EGFR expression in glioma progression in vivo and evaluate targeted therapies for gliomas, we have genetically engineered glioma cells to,visualize the dynamics of EGFR and targeted therapies in real time in vivo. Using engineered lentiviral vectors bearing fusions between EGFR and its exon 2 to 7 deleted variant (EGFRvIII) with green fluorescent protein (GFP) and Renilla luciferase (Rluc), we show that there is a direct correlation between EGFR expression and glioma cell proliferation in the initial stages of glioma progression. To monitor and evaluate EGFR-targeted therapies, we have engineered (a) short hairpin RTNAs (shfUNA) and (b) clinically used monoclonal antibody, cetuximab. Using EGFR-GFP-Rluc/firefly luciferase (Fluc)-DsRed2 glioma model, we show that both shRNAs and cetuximab result in a considerable reduction in glioma cell proliferation in culture and glioma burden in vivo that can be monitored in real time at a cellular resolution. This study serves as a template to follow the role of growth factor receptor expression in tumor progression and to image therapeutic efficacy of targeted therapies in cancer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu FU NCI NIH HHS [P50CA86355, CA86355] NR 33 TC 32 Z9 33 U1 1 U2 5 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 AUG 1 PY 2007 VL 67 IS 15 BP 7335 EP 7342 DI 10.1158/0008-5472.CAN-07-0077 PG 8 WC Oncology SC Oncology GA 197BW UT WOS:000248529300036 PM 17671203 ER PT J AU McCarty, KM Smith, TJ Zhou, W Gonzalez, E Quamruzzaman, Q Mahiuddin, G Ryan, L Su, L Christiani, DC AF McCarty, Kathleert M. Smith, Thomas J. Zhou, Wei Gonzalez, Ernesto Quamruzzaman, Quazzi Mahiuddin, Golam Ryan, Louise Su, Li Christiani, David C. TI Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions SO CARCINOGENESIS LA English DT Article ID DNA-REPAIR GENES; BASAL-CELL CARCINOMA; BREAST-CANCER RISK; ULTRAVIOLET-RADIATION; ANIMAL-MODEL; ENVIRONMENT INTERACTION; CIGARETTE-SMOKING; SODIUM ARSENITE; SUN EXPOSURE; LUNG-CANCER AB Background: Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. Methods: Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Result: No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% Cl = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95 % Cl = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95 % Cl = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (AsplAsn or Asn/Asn) had half i he risk of skin lesions (OR = 0.45, 95 % CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) bad half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. Conclusion: XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Environm Hlth Sci, New Haven, CT 06520 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Dhaka Community Hosp, Dhaka 1217, Bangladesh. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP McCarty, KM (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Environm Hlth Sci, New Haven, CT 06520 USA. EM kathleen.mccarty@yale.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [L30 CA124219, 5T32CA 009330, L30 CA124219-01, T32 CA009330]; NIEHS NIH HHS [ES 00002, ES 05947, ES 11622, P30 ES000002, P42 ES005947, R01 ES011622] NR 51 TC 8 Z9 9 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2007 VL 28 IS 8 BP 1697 EP 1702 DI 10.1093/carcin/bgm099 PG 6 WC Oncology SC Oncology GA 209DY UT WOS:000249370400013 PM 17470448 ER PT J AU Baggish, AL Thompson, PD AF Baggish, Aaron L. Thompson, Paul D. TI The athlete's heart 2007: Diseases of the coronary circulation SO CARDIOLOGY CLINICS LA English DT Article ID ARTERY DISSECTION; SUDDEN-DEATH; ANOMALOUS ORIGIN; VARIANT ANGINA; HYPERTROPHIC CARDIOMYOPATHY; PULMONARY TRUNK; MYOCARDIAL-INFARCTION; SURGICAL-TREATMENT; FOLLOW-UP; CIRCADIAN VARIATION AB The augmentation of myocardial function that accompanies vigorous exercise is dependent upon adequate coronary artery blood flow reserve. Coronary artery pathology may limit coronary blood flow and produce myocardial ischemia. The clinician charged with the care of athletes must have a high index of suspicion for underlying coronary artery pathology when faced with an individual with suggestive symptoms. This article discusses diseases of the coronary circulation relevant to athletes. C1 Hartford Hosp, Henry Low Heart Ctr, Dept Cardiol, Hartford, CT 06102 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Thompson, PD (reprint author), Hartford Hosp, Henry Low Heart Ctr, Dept Cardiol, 7th Floor Jefferson,80 Seymour St, Hartford, CT 06102 USA. EM pthomps@harthosp.org NR 98 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD AUG PY 2007 VL 25 IS 3 BP 431 EP + DI 10.1016/j.ccl.2007.07.003 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 234HE UT WOS:000251150500009 PM 17961797 ER PT J AU Gwack, Y Feske, S Srikanth, S Hogan, PG Rao, A AF Gwack, Yousang Feske, Stefan Srikanth, Sonal Hogan, Patrick G. Rao, Anjana TI Signalling to transcription: Store-operated Ca2+ entry and NFAT activation in lymphocytes SO CELL CALCIUM LA English DT Article DE nuclear factor of activated T cells; CRAC channels; calcineurin; T cell activation; cytokine expression ID T-CELL-RECEPTOR; RNA INTERFERENCE SCREENS; PLASMA-MEMBRANE; CHANNEL FUNCTION; GENE-EXPRESSION; CRAC CHANNEL; CALCIUM-CHANNELS; NUCLEAR-FACTOR; TRP CHANNELS; B-CELLS AB In cells of the immune system that are stimulated by antigen or antigen-antibody complexes, Ca2+ entry from the extracellular medium is driven by depletion of endoplasmic reticulum Ca2+ stores and occurs through specialized store-operated Ca2+ channels known as Ca2+- release-activated Ca2+ (CRAC) channels. The process of store-operated Ca2+ influx is essential for short-term as well as long-term responses by immune-system cells. Short-term responses include mast cell degranulation and killing of target cells by effector cytolytic T cells, whereas long-term responses typically involve changes in gene transcription and include T and B cell proliferation and differentiation. Transcription downstream of Ca2+ influx is in large part funneled through the transcription factor nuclear factor of activated T cells (NFAT), a heavily phosphorylated protein that is cytoplasmic in resting cells, but that enters the nucleus when dephosphorylated by the calmodulin-dependent serine/threonine phosphatase calcineurin. The importance of the Ca2+/calcineurin/NFAT signalling pathway for lymphocyte activation is underscored by the finding that the underlying defect in a family with a hereditary severe combined immune deficiency (SCID) syndrome is a defect in CRAC channel function, store-operated Ca2+ entry, NFAT activation and transcription of cytokines, chemokines and many other NFAT target genes whose transcription is essential for productive immune defence. We recently used a two-pronged genetic approach to identify Orai I as the pore subunit of the CRAC channel. On the one hand, we initiated a positional cloning approach in which we utilised genome-wide single nucleotide polymorphism (SNP) mapping to identify the genomic region linked to the mutant gene in the SCID family described above. In parallel, we used a genome-wide RNAi screen in Drosophila to identify critical regulators of NFAT nuclear translocation and store-operated Ca2+ entry. These approaches, together with subsequent mutational and electrophysiological analyses, converged to identify human Orai I as a pore subunit of the CRAC channel and as the gene product mutated in the SCID patients. (C) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Rm 152,Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 FU NIAID NIH HHS [AI40127, AI066128]; NIGMS NIH HHS [GM075256] NR 82 TC 165 Z9 172 U1 2 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD AUG PY 2007 VL 42 IS 2 BP 145 EP 156 DI 10.1016/j.ceca.2007.03.007 PG 12 WC Cell Biology SC Cell Biology GA 201LQ UT WOS:000248833400005 PM 17572487 ER PT J AU Jing, EX Gesta, S Kahn, CR AF Jing, Enxuan Gesta, Stephane Kahn, C. Ronald TI SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation SO CELL METABOLISM LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; FORKHEAD TRANSCRIPTION; PROTEIN DEACETYLASES; CELL-SURVIVAL; DNA-BINDING; PPAR-GAMMA; GENE; ACETYLATION; HOMOLOG; P53 AB The family of mammalian Sirtuin proteins comprises seven members homologous to yeast Sir2. Here we show that SIRT2, a cytoplasmic sirtuin, is the most abundant sirtuin in adipocytes. Sirt2 expression is downregulated during preadipocyte differentiation in 3T3-L1 cells. Overexpression of SIRT2 inhibits differentiation, whereas reducing SIRT2 expression promotes adipogenesis. Both effects are accompanied by corresponding changes in the expression of PPAR gamma, C/EBP alpha, and genes marking terminal adipocyte differentiation, including Glut4, aP2, and fatty acid synthase. The mechanism underlying the effects of reduced SIRT2 in 3T3-L1 adipocytes includes increased acetylation of FOXO1, with direct interaction between SIRT2 and FOXO1. This interaction enhances insulin-stimulated phosphorylation of FOXO1, which in turn regulates FOXO1 nuclear and cytosolic localization. Thus, Sirt2 acts as an important regulator of adipocyte differentiation through modulation of FOXO1 acetylation/phosphorylation and activity and may play a role in controlling adipose tissue mass and function. C1 Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK060837-05, DK33201, R01 DK033201, R01 DK060837] NR 42 TC 192 Z9 209 U1 0 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD AUG PY 2007 VL 6 IS 2 BP 105 EP 114 DI 10.1016/j.cmet.2007.07.003 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 198ZH UT WOS:000248665500006 PM 17681146 ER PT J AU Lo Celso, C Scadden, DT AF Lo Celso, Cristina Scadden, David T. TI Stem cells remember their grade SO CELL STEM CELL LA English DT Editorial Material ID MURINE HEMATOPOIETIC STEM; PROGENITOR CELLS; IN-VIVO AB The stem cell state is understood based on what cells do in performance assays, crude measures of a highly refined state. In this issue of Cell Stem Cell, Dykstra et al. (2007) reveal stem cell gradation and the extent to which that gradation is retained in stem cell daughters of hematopoietic stem cells. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Stem Cell Inst, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Stem Cell Inst, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu OI Lo Celso, Cristina/0000-0002-1163-4207 NR 9 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD AUG PY 2007 VL 1 IS 2 BP 132 EP 134 DI 10.1016/j.stem.2007.07.011 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XS UT WOS:000251055100004 PM 18371344 ER PT J AU Qyang, Y Martin-Puig, S Chiravuri, M Chen, S Xu, H Bu, L Jiang, X Lin, L Granger, A Moretti, A Caron, L Wu, X Clarke, J Taketo, MM Laugwitz, KL Moon, RT Gruber, P Evans, SM Ding, S Chien, KR AF Qyang, Yibing Martin-Puig, Silvia Chiravuri, MUrali Chen, Shuibing Xu, Huansheng Bu, Lei Jiang, Xin Lin, Lizhu Granger, Anne Moretti, Alessandra Caron, Leslie Wu, Xu Clarke, Jonathan Taketo, Makoto M. Laugwitz, Karl-Ludwig Moon, Randall T. Gruber, Peter Evans, Sylvia M. Ding, Sheng Chien, Kenneth R. TI The renewal and differentiation of Isl1(+) cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway SO CELL STEM CELL LA English DT Article ID EMBRYONIC STEM-CELLS; SMOOTH-MUSCLE; SIGNALING PATHWAY; OUTFLOW TRACT; HEART FIELD; LINEAGES; CARDIOMYOCYTE; EXPRESSION; MOUSE; CARDIOGENESIS AB Isl1(+) cardiovascular progenitors and their downstream progeny play a pivotal role in cardiogenesis and lineage diversification of the heart. The mechanisms that control their renewal and differentiation are largely unknown. Herein, we show that the Wnt/beta-catenin pathway is a major component by which cardiac mesenchymal cells modulate the prespecification, renewal, and differentiation of isl1(+) cardiovascular progenitors. This microenvironment can be reconstituted by a Wnt3a-secreting feeder layer with ES cell-derived, embryonic, and postnatal isl1(+) cardiovascular progenitors. In vivo activation of beta-catenin signaling in isl1(+) progenitors of the secondary heart field leads to their massive accumulation, inhibition of differentiation, and outflow tract (OFT) morphogenic defects. In addition, the mitosis rate in OFT myocytes is significantly reduced following beta-catenin deletion in isl1(+) precursors. Agents that manipulate Wnt signals can markedly expand isl1(+) progenitors from human neonatal hearts, a key advance toward the cloning of human isl1(+) heart progenitors. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA. Childrens Hosp Philadelphia, Cardiac Ctr, Philadelphia, PA 19104 USA. Tech Univ Munich, Klinikum Rechts Isar, Med Klin, D-81675 Munich, Germany. Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98109 USA. Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98109 USA. Univ Washington, Sch Med, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Pl-CPZN 3208,185 Cambridge St, Boston, MA 02114 USA. EM kchien@partners.org RI GRANGER, Anne/A-9748-2010; Bu, Lei/F-4461-2011; Moon, Randall/B-1743-2014; Evans, Sylvia/G-1980-2015; Moretti, Alessandra/O-9271-2015; OI Moon, Randall/0000-0002-9352-1408; Martin-Puig, Silvia/0000-0003-3048-6729 FU Howard Hughes Medical Institute NR 34 TC 194 Z9 202 U1 5 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD AUG PY 2007 VL 1 IS 2 BP 165 EP 179 DI 10.1016/j.stem.2007.05.018 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XS UT WOS:000251055100008 PM 18371348 ER PT J AU Rice, TW Wheeler, AP Bernard, GR Hayden, DL Schoenfeld, DA Ware, LB AF Rice, Todd W. Wheeler, Arthur P. Bernard, Gordon R. Hayden, Douglas L. Schoenfeld, David A. Ware, Lorraine B. CA Inst Health Natl Heart Lung Blood TI Comparison of the SpO(2)/FIO2 ratio and the Pao(2)/FIO2 ratio in patients with acute lung injury or ARDS SO CHEST LA English DT Article DE acute lung injury; ARDS; definition; PaO2/fraction of inspired oxygen ratio ID RESPIRATORY-DISTRESS-SYNDROME; ARTERIAL OXYGEN-SATURATION; BLOOD-GAS VALUES; PULSE OXIMETRY; PROTECTIVE VENTILATION; CONSENSUS CONFERENCE; CLINICAL-TRIAL; DEFINITIONS; OUTCOMES; SCORE AB Background: The diagnostic criteria for acute lung injury (ALI) and ARDS utilize the Pao(2)/ fraction of inspired oxygen (Fio(2)) [P/F] ratio measured by arterial blood gas analysis to assess the degree of hypoxemia. We hypothesized that the pulse oximetric saturation (Spo(2))/Fio(2) (S/F) ratio can be substituted for the P/F ratio in assessing the oxygenation criterion of ALI. Methods: Corresponding measurements of Spo(2) (values <= 97%) and Pao(2) from patients enrolled in the ARDS Network trial of a lower tidal volume ventilator strategy (n = 672) were compared to determine the relationship between S/F and P/F. S/F threshold values correlating with P/F ratios of 200 (ARDS) and 300 (ALI) were determined. Similar measurements from patients enrolled in the ARDS Network trial of lower vs higher positive end-expiratory pressure (n = 402) were utilized for validation. Results: In the derivation data set (2,613 measurements), the relationship between S/F and P/F was described by the following equation: S/F = 64 + 0.84 X (P/F) [p < 0.0001; r = 0.89). An S/F ratio of 235 corresponded with a P/F ratio of 200, while an S/F ratio of 315 corresponded with a P/F ratio of 300. The validation database (2,031 measurements) produced a similar linear relationship. The S/F ratio threshold values of 235 and 315 resulted in 85% sensitivity with 85% specificity and 91% sensitivity with 56% specificity, respectively, for P/F ratios of 200 and 300. Conclusion: S/F ratios correlate with P/F ratios. S/F ratios of 235 and 315 correlate with P/F ratios of 200 and 300, respectively, for diagnosing and following up patients with ALI and ARDS. C1 Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, Nashville, TN 37232 USA. Massachusetts Gen Hosp, ARDS Network Clin Coordinating Ctr, Boston, MA 02114 USA. RP Rice, TW (reprint author), Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, T-1218 MCN, Nashville, TN 37232 USA. EM todd.rice@vanderbi1t.edu FU NHLBI NIH HHS [HL07123, HL70521, HL81332, N01-HR-46054, N01-HR-46064] NR 43 TC 132 Z9 139 U1 0 U2 7 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2007 VL 132 IS 2 BP 410 EP 417 DI 10.1378/chest.07-0617 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 200RE UT WOS:000248779700011 PM 17573487 ER PT J AU Lynch, TJ Bonomi, PD Butts, C Davies, AM Engelman, J Govindan, R Herbst, RS Heymach, JV Johnson, BE Martins, RG Perez-Soler, R Riely, GJ Sandler, AB Sequist, LV Socinski, MA Wong, KK Hart, CS AF Lynch, Thomas J. Bonomi, Philip D. Butts, Charles Davies, Angela M. Engelman, Jeffrey Govindan, Ramaswamy Herbst, Roy S. Heymach, John V. Johnson, Bruce E. Martins, Renato G. Perez-Soler, Roman Riely, Gregory J. Sandler, Alan B. Sequist, Lecia V. Socinski, Mark A. Wong, Kwok-Kin Hart, Carol S. TI Novel agents in the treatment of lung cancer: Fourth Cambridge conference SO CLINICAL CANCER RESEARCH LA English DT Editorial Material AB The Fourth Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was held in Cambridge, Massachusetts on September 29 to 30, 2006, to discuss ongoing clinical research of novel targeted agents for the treatment of non -small cell lung cancer, along with supportive basic and translational research into the molecular pathways implicated in cancer growth and resistance. New information, conclusions, and recommendations considered significant for the field by the program faculty are summarized below and presented at greater length in the individual articles and accompanying discussions that comprise the full conference proceedings. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. InforMEDical, Narberth, PA USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 55 Fruit St,Yawkey,7th Floor,Suite 7601, Boston, MA 02114 USA. EM tlynch@partners.org NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2007 VL 13 IS 15 SU S BP 4583S EP 4588S DI 10.1158/1078-0432.CCR-07-0716 PN 2 PG 6 WC Oncology SC Oncology GA 198KE UT WOS:000248626200001 PM 17671145 ER PT J AU Wong, KK AF Wong, Kwok-Kin TI HKI-272 in non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th Cambridge Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 29-30, 2006 CL Cambridge, MA SP InforMEDical Commun Inc ID GROWTH-FACTOR-RECEPTOR; EGFR KINASE DOMAIN; TYROSINE KINASE; ACQUIRED-RESISTANCE; GENE-MUTATIONS; GEFITINIB; SENSITIVITY; INHIBITORS; ERLOTINIB; TUMORIGENESIS AB Somatic mutations in the kinase domain of the epidermal growth factor receptor (EGFR) gene are found in similar to 10% of lung adenocarcinomas sequenced in the United States and in similar to 30% sequenced in Asia. These mutations are associated with sensitivity to the EGFR inhibitors gefitinib and erlotinib. Many patients who initially respond to erlotinib or gefitinib subsequently relapse. Studies have identified EGFR T790M mutations in tumors from patients who initially responded and then relapsed. The T790M mutation, when combined in vitro with treatment-sensitizing EGFR mutations, permits the continued growth of tumor cells in the presence of erlotinib and gefitinib. HKl-272 is an irreversible EGFR/HER/ErbB inhibitor that has been shown to inhibit the growth of T790M mutant cells in vitro in human lung cancer cell lines and in murine cells transfected with sensitizing EGFR mutations. A phase 1 HKl-272 monotherapy trial in patients with solid tumors is close to completion, Preliminary analyses of the trial, presented at the 2006 annual meeting of American Society of Clinical Oncology, showed that HKl-272 can achieve stable disease control for over 6 months in some patients with non small cell lung cancer that has progressed after treatment with gefitinib or erlotinib. A phase 11 trial of HKl-272 in non -small cell lung cancer patients has been initiated. HKl-272 might offer benefits to non -small cell lung cancer patients who have relapsed after an initial response to erlotinib. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Kwong1@partners.org OI wong, kwok kin/0000-0001-6323-235X NR 24 TC 22 Z9 24 U1 0 U2 1 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 AUG 1 PY 2007 VL 13 IS 15 SU S BP 4593S EP 4596S DI 10.1158/1078-0432.CCR-07-0369 PN 2 PG 4 WC Oncology SC Oncology GA 198KE UT WOS:000248626200003 PM 17671147 ER PT J AU Johnson, BE Jackman, D Janne, PA AF Johnson, Bruce E. Jackman, David Janne, Pasi A. TI Rationale for a phase I trial of erlotinib and the mammalian target of rapamycin inhibitor everolimus (RAD001) for patients with relapsed non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th Cambridge Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 29-30, 2006 CL Cambridge, MA SP InforMEDical Commun Inc ID GROWTH-FACTOR-RECEPTOR; KINASE INHIBITORS; GEFITINIB; SENSITIVITY; MUTATIONS; CHEMOTHERAPY; MTOR; GENE; DETERMINANTS; SURVIVAL AB Background and Rationale: Only 10% of patients with relapsed non -small cell lung cancer (NSCLC) treated with chemotherapy or erlotinib have a partial response to treatment, and nearly all eventually recur and die from their NSCLC. Agents that can block other pathways in addition to the epidermal growth factor receptor signals may improve the therapeutic efficacy of erlotinib. Everolimus (RAD001) is an inhibitor of the mammalian target of rapamycin, which is downstream of initial epidermal growth factor receptor signaling. A trial combining erlotinib with everolimus has been undertaken for patients with relapsed NSCLC. Materials and Methods: Subjects with previously treated NSCLC are treated with increasing doses of daily erlotinib and everolimus given either daily or once weekly. The study's objectives in phase I are to assess the feasibility of combining daily erlotinib and either daily or weekly everolimus, to assess toxicity, and to determine the appropriate dose for subsequent trials. Results: The protocol calls for patients to be treated with escalating daily or weekly everolimus in combination with erlotinib given at doses of 100 mg daily to escalate to 150 mg daily. The dose escalation with both daily and weekly everolimus and erlotinib is ongoing. Conclusions: Everolimus has an appropriate rationale for therapeutic use in combination with erlotinib for patients with NSCLC. This manuscript will review the preclinical rationale for undertaking a study of erlotinib combined with everolimus for patients with relapsed NSCLC. C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Johnson, BE (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. EM bejohnson@partners.org NR 28 TC 27 Z9 27 U1 1 U2 1 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 AUG 1 PY 2007 VL 13 IS 15 SU S BP 4628S EP 4631S DI 10.1158/1078-0432.CCR-07-0717 PN 2 PG 4 WC Oncology SC Oncology GA 198KE UT WOS:000248626200010 PM 17671154 ER PT J AU Engelman, JA AF Engelman, Jeffrey A. TI The role of phosphoinositide 3-kinase pathway inhibitors in the treatment of lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th Cambridge Conference on Novel Agents in the Treatment of Lung Cancer CY SEP 29-30, 2006 CL Cambridge, MA SP InforMEDical Commun Inc ID PTEN EXPRESSION; TUMOR-CELLS; KINASE; SURVIVAL; MTOR; MUTATION; GENE; ACTIVATION; RESISTANCE; GROWTH AB The phosphoinositide 3-kinase signaling network is widely implicated in the pathogenesis of human cancer. This pathway is commandeered by cancer cells to promote unrestrained cellular growth and survival. In this brief review, we speculate about the uses of inhibitors of phosphoinositide 3-kinase signaling as treatments for human cancers,with an emphasis on non-small cell lung cancer. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Signal Transduct, Boston, MA 02215 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Navy Yard,149 13th St, Charlestown, MA 02129 USA. EM jengelman@partners.org NR 29 TC 13 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2007 VL 13 IS 15 SU S BP 4637S EP 4640S DI 10.1158/1078-0432.CCR-07-0653 PN 2 PG 4 WC Oncology SC Oncology GA 198KE UT WOS:000248626200012 PM 17671156 ER PT J AU Liu, WT Makrauer, FL Qamar, AA Janne, PA Odze, RD AF Liu, Weitian Makrauer, Frederick L. Qamar, Amir A. Jaenne, Pasi A. Odze, Robert D. TI Fulminant hepatic failure secondary to erlotinib SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FACTOR RECEPTOR INHIBITORS; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; INDUCED LIVER-INJURY; HEPATOTOXICITY; GEFITINIB; PHARMACOKINETICS; MANAGEMENT; MECHANISM; THERAPY AB Erlotinib is a tyrosine kinase inhibitor recently approved by the Food and Drug Administration for the treatment of non-small-cell lung cancer and pancreatic cancer. We report a case of a patient with stage IV non-small-cell lung cancer who died of fulminant hepatic failure as a result of treatment with erlotinib. C1 Harvard Univ, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liu, WT (reprint author), Harvard Univ, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Brigham & Womens Hosp, Boston, MA 02115 USA. EM wliu3@bics.bwh.harvard.edu NR 24 TC 23 Z9 24 U1 1 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 AUG PY 2007 VL 5 IS 8 BP 917 EP 920 DI 10.1016/j.cgh.2007.04.014 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199SB UT WOS:000248714400009 PM 17625975 ER PT J AU Ioannou, GN Splan, MF Weiss, NS McDonald, GB Beretta, L Lee, SP AF Ioannou, George N. Splan, Meaghan F. Weiss, Noel S. McDonald, George B. Beretta, Laura Lee, Sum P. TI Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; PRIMARY LIVER-CANCER; OF-VETERANS-AFFAIRS; B SURFACE-ANTIGEN; UNITED-STATES; RISK-FACTORS; COMPENSATED CIRRHOSIS; COST-EFFECTIVENESS; DIABETES-MELLITUS; NATURAL-HISTORY AB Background & Aims: Independent predictors of hepatocellular carcinoma in patients with cirrhosis are not well established. Methods: We created a cohort of 2126 patients (41% with hepatitis C virus [HCV] infection) who sought care from all Veterans Affairs health care centers in the northwest United States from 1994 to 2005 and who had a diagnosis of cirrhosis recorded in inpatient or outpatient medical records. Results: During a mean follow-up period of 3.6 years, 100 patients were diagnosed with hepatocellular carcinoma (incidence, 1.3 per 100 patient-years). Important predictors of hepatocellular carcinoma in multivariate models included HCV infection (adjusted hazard ratio [ahr], 3.0; 95% confidence interval [CI], 1.7-5.3); hepatitis B virus (HBV) surface antigen (ahr, 3.3; 95% CI, 1.4-7.7); HBV core antibody (ahr, 1.7; 95% CI, 1.1-2.8); obesity (ahr, 2.5; 95% CI, 1.3 - 4.9), and overweight (ahr, 2.8; 95% CI, 1.5-5.4) relative to patients with a body mass index of < 25 kg/m(2), diabetes (ahr, 1.5; 95% CI, 0.9 - 2.5), and low platelet count (relative to patients with a platelet count of > 266 thousands/mu L, the ahr was 2.1 [95% CI, 0.8-5.6] in patients with a platelet count of 180 - 266 thousands/mu L, 3.3 [95% CI, 1.3 - 8.0] in patients with a platelet count of 111 - 179 thousands/mu L, and the ahr was 4.7 [95% CI, 2.0 - 11.4] in patients with a platelet count of <= 110 thousands/mu L). Conclusions: We identified 6 important predictors of hepatocellular carcinoma in multivariate models (including relatively novel predictors such as increased body mass index, HBV core antibody, and low platelet count), which suggest a means of predicting the risk of hepatocellular carcinoma in patients with cirrhosis and optimizing surveillance strategies. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA 98108 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Hepatitis C Resource Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Ioannou, GN (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, S 111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu RI Lee, Sum Ping/C-4333-2009 NR 38 TC 70 Z9 72 U1 2 U2 6 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 AUG PY 2007 VL 5 IS 8 BP 938 EP 945 DI 10.1016/j.cgh.2007.02.039 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199SB UT WOS:000248714400012 PM 17509946 ER PT J AU Apicella, C Dowty, JG Dite, GS Jenkins, MA Senle, RT Daly, MB Andrulis, IL John, EM Buys, SS Li, FP Glendon, G Chung, W Ozcelik, H Miron, A Kotar, K Southey, MC Foulkes, WD Hopper, JL AF Apicella, C. Dowty, J. G. Dite, G. S. Jenkins, M. A. Senle, R. T. Daly, M. B. Andrulis, I. L. John, E. M. Buys, S. S. Li, F. P. Glendon, G. Chung, W. Ozcelik, H. Miron, A. Kotar, K. Southey, M. C. Foulkes, W. D. Hopper, J. L. TI Validation study of the LAMBDA model for predicting the BRCA1 or BRCA2 mutation carrier status of North American Ashkenazi Jewish women SO CLINICAL GENETICS LA English DT Article DE Ashkenazi Jewish; BRCA1; BRCA2; breast cancer; mutations; ovarian ID BREAST-CANCER PATIENTS; OVARIAN-CANCER; SUSCEPTIBILITY GENES; UNITED-STATES; COMMON BRCA1; RISK; PREVALENCE; PHENOTYPE; 185DELAG; JEWS AB LAMBDA is a model that estimates the probability an Ashkenazi Jewish (AJ) woman carries an ancestral BRCA1 or BRCA2 mutation from her personal and family cancer history. LAMBDA is relevant to clinical practice, and its implementation does not require a computer. It was developed principally from Australian and UK data. We conducted a validation study using 1286 North American AJ women tested for the mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2. Most had a personal or family history of breast cancer. We observed 197 carriers. The area under the receiver operator characteristic (ROC) curve ( a measure of ranking) was 0.79 [95% confidence interval (CI) = 0.77 - 0.81], similar to that for the model-generating data (0.78; 95% CI = 0.75 - 0.82). LAMBDA predicted 232 carriers (18% more than observed; p = 0.002) and was overdispersed ( p = 0.009). The Bayesian computer program BRCAPRO gave a similar area under the ROC curve ( 0.78; 95% CI 0.76-0.80), but predicted 367 carriers (86% more than observed; p < 0.0001), and was substantially overdispersed ( p, 0.0001). Therefore, LAMBDA is comparable to BRCAPRO for ranking AJ women according to their probability of being a BRCA1 or BRCA2 mutation carrier and is more accurate than BRCAPRO which substantially overpredicts carriers in this population. C1 Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Fox Chase Canc Ctr, Dept Populat Sci, Philadelphia, PA 19111 USA. Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. No Calif Canc Ctr, Dept Epidemiol, Fremont, CA USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. McGill Univ, Program Canc Genet, Dept Oncol, Montreal, PQ H3A 2T5, Canada. McGill Univ, Program Canc Genet, Dept Human Genet, Montreal, PQ H3A 2T5, Canada. Univ Melbourne, Dept Pathol, Carlton, Vic 3053, Australia. RP Hopper, JL (reprint author), Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, 723 Swanston St, Carlton, Vic 3053, Australia. EM j.hopper@unimelb.edu.au RI Andrulis, Irene/E-7267-2013; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Dite, Gillian/0000-0002-2448-2548; Dowty, James/0000-0003-2383-0886; foulkes, william/0000-0001-7427-4651 FU NCI NIH HHS [CA95003, U01 CA069417, U01 CA069417-10] NR 43 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD AUG PY 2007 VL 72 IS 2 BP 87 EP 97 DI 10.1111/j.1399-0004.2007.00841.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 197DH UT WOS:000248533500004 PM 17661812 ER PT J AU Waid, DM Wagner, RJ Putnam, A Vaitaitis, GM Pennock, ND Calverley, DC Gottlieb, P Wagner, DH AF Waid, Dan M. Wagner, Rebecca J. Putnam, Amy Vaitaitis, Gisela M. Pennock, Nathan D. Calverley, David C. Gottlieb, Peter Wagner, David H., Jr. TI A unique T cell subset described as CD4(10)CD40(+) T cells (T-CD40) in human type 1 diabetes SO CLINICAL IMMUNOLOGY LA English DT Article DE type 1 diabetes; auto-reactive T cells; autoimmunity; CD40 ID CLASS-II TETRAMERS; AT-RISK SUBJECTS; CHEMOKINE RECEPTORS; PERIPHERAL-BLOOD; INCREASED EXPRESSION; TCR REVISION; CUTTING EDGE; LYMPHOCYTES; CD40; AUTOIMMUNITY AB Human T1D pancreatic lymph nodes contain diabetes-autoantigen responsive T cells but identification of such T cells in the periphery has proven difficult. Here we describe a unique T cell subset defined by CD4(10) and CD40 expression (T-CD40) that is significantly expanded in peripheral blood of T1D but not control or T2D subjects. The HLA-DR3 and DR4 alleles are considered high risk factors for T1D and TCD40 expansion occurs in T1D subjects carrying HLA DR3 or DR4 haplotypes but, T1D subjects who do not carry either DR3 or DR4 haplotypes still have an expanded percentage of TCD40 cells. Non-autoimmune subjects, even DR3(+) and DR4(+), do not have elevated percentages of T-CD40 cells. The majority of T-CD40 cells in T1D carry a memory phenotype and a portion of those proliferates when exposed to diabetes-associated self-antigens. A greater number of memory T-CD40 cells express CXCR3 when compared to CD40(-) memory cells and that number is significantly expanded in T1D compared to control subjects. If only total CD4(+) T cells are compared no difference in CXCR3 is seen. Furthermore, T-CD40 cells produce a Th1, pro-inflammatory cytokine profile. In healthy controls, T-CD40 cells have equally Th1 and Th2 profiles. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Colorado, Dept Med, Denver, CO 80262 USA. Hlth Sci Ctr, Denver, CO 80262 USA. Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. Hlth Sci Ctr, Aurora, CO USA. Univ Calif San Francisco, UCSF Diabet Ctr, San Francisco, CA USA. Denver VA Med Ctr, Med & Res Serv, Denver, CO 80220 USA. RP Wagner, DH (reprint author), Univ Colorado, Dept Med, 4200 E 9th Ave, Denver, CO 80262 USA. EM David.Wagner@UCHSC.edu NR 43 TC 30 Z9 31 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 AUG PY 2007 VL 124 IS 2 BP 138 EP 148 DI 10.1016/j.clim.2007.05.003 PG 11 WC Immunology SC Immunology GA 194VE UT WOS:000248371100004 PM 17560173 ER PT J AU Lee, AI Munshi, NC AF Lee, Alfred Ian Munshi, Nikhil C. TI Integration of novel agents into treatment of myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article DE bortezomib; lenalidomide; thalidomide ID RELAPSED MULTIPLE-MYELOMA; THALIDOMIDE PLUS DEXAMETHASONE; BONE-MARROW MICROENVIRONMENT; OVERCOMES DRUG-RESISTANCE; STEM-CELL TRANSPLANTATION; PROTEASOME INHIBITOR BORTEZOMIB; INDUCTION TREATMENT PRIOR; HIGH-DOSE DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; COMBINATION THERAPY AB More than 150 years have passed since the first treatments of multiple myeloma were initiated. The past decade has seen a renaissance in the generation of therapies for myeloma as a result of heightened understanding of the molecular pathogenesis of the disease. This review article highlights the development and incorporation of the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide into standard myeloma treatment regimens. We also discuss the creation of multiple other myeloma agents currently in phase I/II testing and designed to target specific pathways in myeloma physiology. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM nikhil-muiishi@dfci.harvard.edu NR 74 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD AUG PY 2007 VL 7 SU 5 BP S215 EP S221 PG 7 WC Oncology SC Oncology GA 211WS UT WOS:000249554600006 PM 17877847 ER PT J AU Treon, SP Hatjiharissi, E Leleu, X Moreau, AS Roccaro, A Hunter, ZR Sournerai, JD Ciccarelli, B Xu, L Sacco, A Ngo, HT Jia, XY Yang, C Adarnia, S Ho, AW Santos, DD Tournilhac, O Manning, RJ Leduc, R O'Connor, K Nelson, M Patterson, CJ Ghobrial, I AF Treon, Steven P. Hatjiharissi, Evdoxia Leleu, Xavier Moreau, Anne-Sophie Roccaro, Aldo Hunter, Zachary R. Sournerai, Jacob D. Ciccarelli, Bryan Xu, Lian Sacco, Antonio Ngo, Hai T. Jia, Xiaoying Yang, Cao Adarnia, Sophia Ho, Allen W. Santos, Daniel D. Tournilhac, Olivier Manning, Robert J. Leduc, Renee O'Connor, Kelly Nelson, Marybeth Patterson, Christopher J. Ghobrial, Irene TI Novel agents in the treatment of Waldenstrom's macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article DE alemtuzumab; APRIL/BLyS; bortezomib; lenalidomide; SGN-70; Waldenstrom's macroglobulinemia ID B-LYMPHOCYTE STIMULATOR; PROTEASOME INHIBITOR BORTEZOMIB; CASPASE-DEPENDENT APOPTOSIS; MONOCLONAL-ANTIBODY SGN-70; VIVO ANTITUMOR-ACTIVITY; MULTIPLE-MYELOMA CELLS; IN-VITRO; PHASE-II; CLINICAL ACTIVITY; LYMPHOPLASMACYTIC CELLS AB Waldenstrom's macroglobulinemia is a B-cell disorder characterized by bone marrow infiltration with lymphoplasmacytic cells and demonstration of an immunoglobulin M monoclonal gammopathy. Despite advances in therapy, Waldenstrom's macroglobulinemia remains incurable. As such, novel therapeutic agents are needed for the treatment of Waldenstrom's macroglobulinemia. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of Waldenstrom's macroglobulinemia so as to better target therapeutics for this malignancy. Importantly, as part of these efforts, we have prioritized the development of stem cell-sparing drugs because autologous stem cell transplantation remains a viable salvage option in Waldenstrom's macroglobulinemia. These efforts have led to the development of several novel agents for treating Waldenstrom's macroglobulinemia, including bortezomib; monoclonal antibodies and/or blocking protein targeting CD40, CD52, or CD70, a proliferation-inducing ligand and B-lymphocyte stimulator; the immunomodulator thalidomide as an enhancer of rituximab activity, as well as agents interfering with stem cell factor, phosphatidylinositol 3-kinase/Akt, phosphodiesterase, cholesterol, and protein kinase C P signaling. This report provides an update on biologic studies and clinical efforts for the development of these novel agents in the treatment of Waldenstrom's macroglobulinemia. C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulenemia, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulenemia, 44 Binney St, Boston, MA 02115 USA. EM steven-treon@dfci.harvard.edu RI Ho, Allen/B-3017-2011; Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU NCI NIH HHS [K23CA087977-03] NR 50 TC 10 Z9 10 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD AUG PY 2007 VL 7 SU 5 BP S199 EP S206 DI 10.3816/CLM.2007.s.023 PG 8 WC Oncology SC Oncology GA 211WS UT WOS:000249554600004 PM 17877845 ER PT J AU Paeng, CH Sprague, M Jackevicius, CA AF Paeng, Christine H. Sprague, Michael Jackevicius, Cynthia A. TI Interaction between warfarin and cranberry juice SO CLINICAL THERAPEUTICS LA English DT Article DE warfarin; cranberry juice; anticoagulation; drug interaction AB Introduction: Warfarin is commonly used to treat or prevent thromboembolic events. Cranberry Juice has been suggested to have an interaction with warfarin. However, there have been few reported cases of warfarin-cranberry juice interaction. Case summary: A 78-year-old, 86-kg man receiving warfarin at a total weekly dose of 45 mg for atrial fibrillation presented at the Bakersfield Healthcare Center of the VA Greater Los Angeles Healthcare System with an international normalized ratio (INR) of 6.45, having reported drinking a half gallon of cranberry/apple juice in the week prior to the elevated INR. After discontinuation of the cranberry Juice, maintaining the warfarin dose for 5 days, and resuming the warfarin at a total weekly dose of 40 mg, the INR returned to the therapeutic range of 2 to 3. Discussion: Possible warfarin-cranberry Juice interactions have been reported in the literature. Case reports illustrate INR elevation associated with cranberry juice ingestion concomitantly with warfarin administration and may be associated with bleeding (eg, pericardial, gastrointestinal). In the present case report, cranberry juice was the most likely cause of the patient's elevated INR. The Naranjo probability scale score was 3, suggesting that there was a possible interaction between warfarin and cranberry juice, while the modified Naranjo scale score adapted for anticoagulants was 5, rating the interaction as probable. Conclusion: The combination of warfarin administration and cranberry juice ingestion appeared to be associated with an elevated INR without bleeding in this elderly patient. (Clin Ther. 2007;29:1730-1735) Copyright (c) 2007 Excerpta Medica, Inc. C1 Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. Bakersfield Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Bakersfield, CA USA. Univ Pacific, Sch Pharm, Stockton, CA 95211 USA. Univ So Calif, Sch Pharm, Los Angeles, CA USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E 2nd St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu NR 16 TC 22 Z9 23 U1 1 U2 8 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD AUG PY 2007 VL 29 IS 8 BP 1730 EP 1735 DI 10.1016/j.clinthera.2007.08.018 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 213QT UT WOS:000249682900018 PM 17919554 ER PT J AU Castle, SC Uyemura, K Fulop, T Makinodan, T AF Castle, Steven C. Uyemura, Koichi Fulop, Tamas Makinodan, Takashi TI Host Resistance and Immune Responses in Advanced Age SO CLINICS IN GERIATRIC MEDICINE LA English DT Article AB Immunosenescence results in populating immune tissues with less functional T cells, and perhaps B cells dendritic cells, that do not function well and produce more type 2 cytokines and fewer type I cytokines. Impaired immunity, distinct from immunosenescence, correlates more with disease burden than chronologic age. Older adults who have chronic diseases or chronic infections are more susceptible to common infections and have poor vaccine responses. Understanding specific mechanisms and targeting interventions are dependent on research to resolve the relationship between frailty-associated impaired immunity and the role of chronic infection versus immunosenescence in developing impaired immunity. C1 [Castle, Steven C.; Uyemura, Koichi; Makinodan, Takashi] Univ Calif Los Angeles, Sch Med, VA Greater Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. [Fulop, Tamas] Univ Sherbrooke, Div Geriatr, Res Ctr Aging, Program Immunol, Sherbrooke, PQ J1K 2R1, Canada. RP Castle, SC (reprint author), Univ Calif Los Angeles, Sch Med, VA Greater Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Mail Code 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM steven.castle@med.va.gov NR 70 TC 38 Z9 40 U1 1 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 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2007 VL 23 IS 3 BP 463 EP + DI 10.1016/j.cger.2007.03.005 PG 18 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA V95WW UT WOS:000206481400002 PM 17631228 ER PT J AU Britton, JC Gold, AL Feczko, EJ Rauch, SL Williams, D Wright, CI AF Britton, Jennifer C. Gold, Andrea L. Feczko, Eric J. Rauch, Scott L. Williams, Danielle Wright, Christopher I. TI D-cycloserine inhibits amygdala responses during repeated presentations of faces SO CNS SPECTRUMS LA English DT Article ID FEAR-POTENTIATED STARTLE; AGONIST D-CYCLOSERINE; GLUCOSE-METABOLISM; PREFRONTAL CORTEX; CONDITIONED FEAR; NEUTRAL FACES; EXTINCTION; ANTIDEPRESSANT; HABITUATION; DEPRESSION AB Introduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined. Methods:The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0 +/- 8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks. Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected. Conclusion:This finding may have relevance for testing treatments of anxiety and depression. C1 Massachusetts Gen Hosp, Dept Pathol, Psychiat Neuroimaging Res Program, Lab Aging & Emot, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Martinos Biomed Imaging Ctr, Charlestown, MA 02114 USA. Harvard Univ, Med Ctr, Boston, MA USA. Yale Univ, Psychiat Neuroimaging Res Program, Martinos Med Imaging Ctr, New Haven, CT USA. Washington Univ, St Louis, MO USA. McLean Hosp, Martinos Biomed Imaging Ctr, Psychiat Neuroimaging Res Program, Belmont, MA 02178 USA. Suffolk Univ, Boston, MA 02114 USA. Brigham & Womens Hosp, Psychiat Neuroimaging Res Program, Martinos Biomed Imaging Ctr, Div Cognit & Behav Neurol,Dept Neurol, Boston, MA USA. Vertex Pharmaceut Inc, Cambridge, MA USA. RP Wright, CI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Psychiat Neuroimaging Res Program, Lab Aging & Emot, Thirteenth St,Bldg 149, Charlestown, MA 02129 USA. EM ciwright@partners.org RI Britton, Jennifer/J-4501-2013; OI Gold, Andrea/0000-0003-4447-776X FU NIA NIH HHS [R01AG030311]; NIMH NIH HHS [K23MH64806] NR 45 TC 10 Z9 10 U1 2 U2 2 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 AUG PY 2007 VL 12 IS 8 BP 600 EP 605 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 214KX UT WOS:000249737500009 PM 17667888 ER PT J AU Zelinski, AC Wald, LL Setsompop, K Alagappan, V Gagoski, BA Goyal, VK Hebrank, F Fontius, U Schmitt, F Adalsteinsson, E AF Zelinski, Adam C. Wald, Lawrence L. Setsompop, Kawin Alagappan, Vijayanand Gagoski, Borjan A. Goyal, Vivek K. Hebrank, Franz Fontius, Ulrich Schmitt, Franz Adalsteinsson, Elfar TI Comparison of three algorithms for solving linearized systems of parallel excitation RF waveform design equations: Experiments on an eight-channel system at 3 tesla SO CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING LA English DT Article DE parallel excitation; cancellation artifacts; RF acceleration; RF coil array; conjugate-gradient methods ID REDUCED B-1 INHOMOGENEITY; LEAST-SQUARES; COILS; PULSE; SAR; TRANSMISSION; CHANNELS; VALUES; LSQR; HEAD AB Three algorithms for solving linearized systems of RF waveform design equations for calculating accelerated spatially-tailored excitations on parallel excitation MRI systems are presented. Thei r artifact levels, computational speed, and RF peak and root-mean-square (RMS) voltages are analyzed. An SVD-based inversion method is compared with conjugate gradient least squares (CGLS) and least squares OR (LSOR), two iterative algorithms designed to solve large linear systems. The excitation pulses calculated using these methods are used in both Bloch simulations and imaging experiments on an actual eight-channel parallel excitation coil array implemented on a 3T human scanner. Specifically, RF waveforms are designed for accelerated 2D spiral k-space trajectories to produce a variety of 2D target excitations and for a 3D spokes trajectory to produce a uniform thin-slice excitation. Overall, these experiments show that waveforms designed using LSOR and CGLS have significantly lower peak and RMS waveform voltages and produce excitations with fewer artifacts than those generated by the SVD-based method. (c) 2007 Wiley Periodicals, Inc. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. Siemens Med Solut, Erlangen, Germany. RP Zelinski, AC (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM zelinski@mit.edu; elfar@mit.edu RI Goyal, Vivek/B-7955-2008; Adalsteinsson, Elfar/F-2477-2010; Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009 OI Goyal, Vivek/0000-0001-8471-7049; Setsompop, Kawin/0000-0003-0455-7634; NR 37 TC 5 Z9 5 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-5031 J9 CONCEPT MAGN RESON B JI Concepts Magn. Reson. Part B PD AUG PY 2007 VL 31B IS 3 BP 176 EP 190 DI 10.1002/cmr.b.20093 PG 15 WC Chemistry, Physical; Instruments & Instrumentation; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Chemistry; Instruments & Instrumentation; Physics; Spectroscopy GA 194YU UT WOS:000248380500005 ER PT J AU Certain, H Mueller, M Jagodzinski, T Fleming, M AF Certain, H. Mueller, M. Jagodzinski, T. Fleming, M. TI Intimate partner violence in postpartum women SO CONTRACEPTION LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD AUG PY 2007 VL 76 IS 2 BP 168 EP 168 DI 10.1016/j.contraception.2007.05.045 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 197DS UT WOS:000248534800056 ER PT J AU Ware, LB Matthay, MA Parsons, PE Thompson, BT Januzzi, JL Eisner, MD AF Ware, Lorraine B. Matthay, Michael A. Parsons, Polly E. Thompson, B. Taylor Januzzi, James L. Eisner, Mark D. CA National Heart Lung Blood Inst Acu TI Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; protein C; plasminogen activator inhibitor-1; coagulation; fibrinolysis ID ACTIVATED PROTEIN-C; ALVEOLAR FLUID CLEARANCE; SEVERE SEPSIS; MYOCARDIAL-INFARCTION; ANGINA-PECTORIS; RISK-FACTORS; ABNORMALITIES; INHIBITOR-1; MORTALITY; VENTILATION AB Objective: The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking. Design: Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculate or each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. Setting: Ten university medical centers. Patients: The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. Measurements and Main Results: Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. Conclusions: Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies. C1 Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Environm & Occupat Med, San Francisco, CA 94143 USA. Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Fletcher Allen Hlth Care, Burlington, VT USA. Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Ware, LB (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. EM lorraine.ware@vanderbilt.edu OI Wiedemann, Herbert/0000-0002-4587-4401 FU NHLBI NIH HHS [N01HR46054, K08 HL070521, N0-1 HR 46055, N0-1 HR 46057, N0-1 HR 46059, N0-1 HR 46060, N0-1 HR 46062, N0-1 HR 46064, R01 HL051856, N0-1 HR 46056, HL 04201, HL 51856, HL 70521, HL081332, K23 HL004201, N0-1 HR 46054, N0-1 HR 46058, N0-1 HR 46061, N0-1 HR 46063, P50 HL074005, P50 HL74005, R37 HL051856, R37 HL051856-14, U01 HL081332] NR 40 TC 143 Z9 151 U1 0 U2 4 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 AUG PY 2007 VL 35 IS 8 BP 1821 EP 1828 DI 10.1097/01.CCM.0000275386.95968.5F PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 193CP UT WOS:000248251600002 PM 17667242 ER PT J AU Conrad, C Gupta, R Mohan, H Niess, H Bruns, CJ Kopp, R von Luettichau, I Guba, M Heeschen, C Jauch, KW Huss, R Nelson, PJ AF Conrad, Claudius Gupta, Rashmi Mohan, Hema Niess, Hanno Bruns, Christiane J. Kopp, Reinhard von Luettichau, Irene Guba, Markus Heeschen, Christopher Jauch, Karl-Walter Huss, Ralf Nelson, Peter J. TI Genetically engineered stem cells for therapeutic gene delivery SO CURRENT GENE THERAPY LA English DT Review DE cell Therapy; progenitor cells; tissue engineering; gene delivery; stem cell recruitment; cell differentiation; angiogenesis; tumor stem cell ID ADENOASSOCIATED VIRAL VECTORS; SEVERE COMBINED IMMUNODEFICIENCY; EFFICIENT NONVIRAL TRANSFECTION; SITE-SPECIFIC RECOMBINATION; HUMAN ADIPOSE-TISSUE; IN-VIVO; ADENOVIRUS VECTORS; TRANSGENIC MICE; BONE-MARROW; QUANTITATIVE-ANALYSIS AB Stem cell and gene therapy approaches have held out much hope for the development of new tools to treat disease. Therapeutic approaches based on these methods have only rarely found their way into the clinic. The linking of stem cell therapy with selective gene therapy enhances therapeutic options for the regeneration or replacement of diseased or missing cells. This review focuses on the rationale and preliminary results of combining stem cell and gene therapy. Special emphasis is placed on various molecular techniques currently used to genetically engineer stem cells. Viral and nonviral genes delivering technologies are detailed as are techniques for the modulation of gene expression in the context of stem cell recruitment and differentiation. Finally potential clinical applications for this new therapeutic strategy are discussed. C1 Univ Munich, Klinikum Grosshadern, Dept Surg, D-80539 Munich, Germany. Max Planck Inst Biochem, Martinsried, Germany. Roch Diagnost GmbH, Penzberg, Germany. Univ Munich, Dept Pathol, D-80539 Munich, Germany. Univ Munich, Policlin, Klinikum Innenstadt, D-80539 Munich, Germany. Max Planck Inst Neurobiol, Martinsried, Germany. Tech Univ Munich, Dept Pediat, Munich, Germany. RP Conrad, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM Cconrad1@partners.org NR 101 TC 39 Z9 39 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 J9 CURR GENE THER JI Curr. Gene Ther. PD AUG PY 2007 VL 7 IS 4 BP 249 EP 260 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 197PN UT WOS:000248568000003 PM 17969558 ER PT J AU Wang, JQ Brownell, AL AF Wang, Ji-Quan Brownell, Anna-Liisa TI Development of metabotropic glutamate receptor ligands for neuroimaging SO CURRENT MEDICAL IMAGING REVIEWS LA English DT Review DE allosteric modulator; glutamate; metabotropic glutamate receptor; mGluR5; positron emission tomography; tracer ID POSITIVE ALLOSTERIC MODULATORS; POSITRON-EMISSION-TOMOGRAPHY; NONCOMPETITIVE MGLUR1 ANTAGONISTS; IN-VIVO; HIGHLY POTENT; GLUTAMATE-RECEPTOR-2 MGLU2; ANXIOLYTIC ACTIVITY; PHARMACOLOGICAL CHARACTERIZATION; HUNTINGTONS-DISEASE; BINDING-SITE AB Metabotropic glutamate receptors (mGluRs) belong to a superfamily of G protein coupled receptors. In the central nervous system (CNS), mGluRs modulate glutamatergic neurotransmission and are considered to affect also on dopaminergic and adrenergic neurotransmission. MGluRs have various physiological functions in CNS and are suggested to be involved in a number of neurological disorders. Receptor ligands binding to mGluRs are also considered as potential therapeutic agents. Classic competitive ligands, which are amino acid derivatives, bind to the orthosteric binding site as endogenous glutamate. It is believed that developing highly selective competitive agonists and antagonists for specific mGluR subtypes has been exceedingly difficult because of the high conservation of the glutamate binding site across members of this receptor family and the restricted structural requirements for pharmacophores that occupy the binding pocket. Another shortcoming of this kind of ligands is that the carboxyl and amino groups make them too polar to penetrate the blood brain barrier. Although these ligands have had and still have important roles in elucidating physiological and pathophysiological properties of mGluRs, their poor selectivity within group presupposes some knowledge of complexity. In addition, their poor CNS penetration limits their candidacy as promising radiotracers; for in vivo imaging of mGluRs. Over the last decade, a number of non-competitive mGluR ligands, which are structurally diverse and bind to mGluRs in the allosteric binding sites located in the seven strand transmembrane domain, have been identified. These include negative, positive and neutral allosteric modulators. Modulating mGlu receptor activity through an allosteric binding site is a relatively new strategy with the first example appeared in 1996. Based on these modulators, a number of radiotracers useful for imaging specific metabotropic glutamate receptors have been developed and their in vivo biological properties have been characterized. We have developed five ligands for PET imaging of metabotropic glutamate subgroup 5 receptors and investigated mGluR functions in animal models of different neurodegenerative disorders. In this review we evaluate our data in comparison to the theoretical and experimental aspects of developing selective and sensitive imaging ligands for in vivo imaging. Emphasis will be given to those highly potent and subtype selective allosteric modulators which are good candidates for radiolabeling with fluorine-18 and carbon-11. C1 Massachusetts Gen Hosp, Dept Radiol, Expt PET Lab, Boston, MA 02114 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Expt PET Lab, Bartlett Hall 504R, Boston, MA 02114 USA. EM abrownell@partners.org NR 97 TC 5 Z9 5 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4056 J9 CURR MED IMAGING REV JI Curr. Med. Imaging Rev. PD AUG PY 2007 VL 3 IS 3 BP 186 EP 205 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 193BV UT WOS:000248249500006 ER PT J AU Solt, K Forman, SA AF Solt, Ken Forman, Stuart A. TI Correlating the clinical actions and molecular mechanisms of general anesthetics SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE amnesia; gamma-aminobutyric acid receptor; general anesthesia; glutamate receptor; hypnosis; immobility AB Purpose of review To summarize recent in-vitro and in-vivo research on molecular mechanisms of general anesthetics' actions. Recent findings Classes of general anesthetics with distinct clinical profiles appear to induce amnesia, hypnosis, and immobility via different molecular targets. Propofol, etomidate, and barbiturates produce profound amnesia and hypnosis, but weak immobility, by enhancing the activity of specific gamma-aminobutyric acid typeA receptors. In contrast, nitrous oxide, xenon, and ketamine produce analgesia, but weak hypnosis and amnesia, by inhibiting glutamate and nicotinic receptors and activating potassium 'leak' channels such as TREK-1. Volatile halogenated anesthetics show little selectivity for molecular targets. They act on all the channels mentioned above, and other targets such as glycine receptors and mediators of neurotransmitter release. Summary Several clinically distinct 'anesthetic states' are induced by different classes of drugs acting on neuronal circuits via different molecular targets. Understanding the mechanisms underlying the therapeutic and toxic actions of general anesthetics helps us reframe the 'art' of anesthesia into more of a 'science'. These studies also enhance efforts to develop new drugs with improved clinical utility. C1 [Solt, Ken; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Gray 444, Boston, MA 02114 USA. [Solt, Ken; Forman, Stuart A.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Gray 444, Boston, MA 02114 USA. EM saforman@partners.org OI Solt, Ken/0000-0001-5328-2062 NR 54 TC 53 Z9 61 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD AUG PY 2007 VL 20 IS 4 BP 300 EP 306 DI 10.1097/ACO.0b013e32816678a5 PG 7 WC Anesthesiology SC Anesthesiology GA V42SE UT WOS:000209632700004 PM 17620835 ER PT J AU Pino, RM AF Pino, Richard M. TI The nature of anesthesia and procedural sedation outside of the operating room SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE capnography; deep sedation; moderate sedation; monitored anesthesia care; nonanesthesia sedation; procedural sedation; propofol AB Purpose of review Procedural sedation and monitored anesthesia care have become increasingly common in locations outside of the operating room. The different types of procedures are presented along with pertinent safety issues with the use of different drug combinations. Recent findings Based on the annual data from one hospital, of approximately 63 000 patients undergoing diagnostic or therapeutic procedures under sedation or anesthesia, 41% were sedated by non-anesthesiologists. Monitored anesthesia care was given to 0.4% of patients outside of the operating room. Events associated with monitored anesthesia care have been related to age, American Society of Anesthesiologists physical status, and obesity. Without the use of capnography, significant delays in the detection of apnea were demonstrable. Respiratory compromise with propofol for sedation appears less than that described for sedation using opiates and benzodiazepines. Summary The number and types of procedures done outside of the operating room are steadily increasing. Sedation for these is often provided by nonanesthesiologists. A quality assurance system dedicated to track events associated with procedural sedation and anesthesia done outside of the operating room is instrumental for the maintenance of exemplary quality of sedation and safety of our patients. C1 [Pino, Richard M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. RP Pino, RM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM rpino@partners.org NR 22 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD AUG PY 2007 VL 20 IS 4 BP 347 EP 351 PG 5 WC Anesthesiology SC Anesthesiology GA V42SE UT WOS:000209632700013 ER PT J AU Hung, AY Schwarzschild, MA AF Hung, Albert Y. Schwarzschild, Michael A. TI Clinical trials for neuroprotection in Parkinson's disease: overcoming angst and futility? SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE clinical trial; futility study; neuroprotection; Parkinson's disease ID PROGRAMMED CELL-DEATH; DOUBLE-BLIND; COENZYME Q(10); NEURODEGENERATIVE DISORDERS; PROTEASOME INHIBITION; DELAYED-START; PILOT TRIAL; PROGRESSION; MODEL; SELEGILINE AB Purpose of review To summarize recently published results of neuroprotection trials for Parkinson's disease, and discuss them in the context of evolving concepts in clinical study design and animal models. Recent findings Despite compelling preclinical evidence from laboratory models suggesting potential neuroprotective benefits, the antioxidant, antiapoptotic, antiexcitotoxic, immunomodulatory and neurotrophic agents studied to date have not shown clear benefit in human studies. The futility study design, an alternative approach focused on efficiently excluding less promising compounds, has been adopted recently to investigate four candidate neuroprotectants. A delayed-start trial design has also been introduced in a study of the monoamine oxidase inhibitor rasagiline, demonstrating a possible neuroprotective effect as well as its clear symptomatic benefit. In parallel with these clinical innovations, preclinical research initiatives are identifying new animal models that more closely resemble the clinical course and pathology of Parkinson's disease. Summary Angst over disappointing results of neuroprotection trials in Parkinson's disease has engendered efforts to refine animal models at one end of the therapeutics pipeline, and to optimize clinical trial design at the other. Building on new insights into the genetics, epidemiology and pathogenesis of Parkinson's disease, these recent improvements in 'translational infrastructure' will enhance the prospects of achieving the critical goal of slowing the progression of disability. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. MassGen Inst Neurodegenerat Dis, Boston, MA USA. RP Hung, AY (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM ahung@partners.org FU NINDS NIH HHS [NS054978] NR 68 TC 27 Z9 27 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD AUG PY 2007 VL 20 IS 4 BP 477 EP 483 DI 10.1097/WCO.0b013e32826388d6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 195NL UT WOS:000248418800016 PM 17620885 ER PT J AU Jiang, S Zhou, XB Kirchhausen, T Wong, STC AF Jiang, Shan Zhou, Xiaobo Kirchhausen, Tom Wong, Stephen T. C. TI Detection of molecular particles in live cells via machine learning SO CYTOMETRY PART A LA English DT Article DE particle detection; machine learning; Haar features; signal-to-noise ratio ID CLATHRIN-COATED PITS; MEDIATED ENDOCYTOSIS; MAMMALIAN-CELLS; DYNAMICS; CYTOSKELETON; ADAPTERS; NETWORK; ACTIN AB Clathrin-coated pits play an important role in removing proteins and lipids from the plasma membrane and transporting them to the endosomal compartment. It is, however, still unclear whether there exist "hot spots" for the formation of Clathrin-coated pits or the pits and arrays formed randomly on the plasma membrane. To answer this question, first of all, many hundreds of individual pits need to be detected accurately and separated in live-cell microscope movies to capture and monitor how pits and vesicles were formed. Because of the noisy background and the low contrast of the live-cell movies, the existing image analysis methods, such as single threshold, edge detection, and morphological operation, cannot be used. Thus, this paper proposes a machine learning method, which is based on Haar features, to detect the particle's position. Results show that this method can successfully detect most of particles in the image. In order to get the accurate boundaries of these particles, several post-processing methods are applied and signal-to-noise ratio analysis is also performed to rule out the weak Spots. (C) 2007 International Society for Analytical Cytology C1 Harvard Univ, Sch Med, HCNR Ctr Bioinformat, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02215 USA. Tsing Hua Univ, Dept Math Sci, Beijing 100084, Peoples R China. Brigham & Womens Hosp, Funct & Mol Imaging Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02215 USA. RP Zhou, XB (reprint author), Harvard Univ, Sch Med, HCNR Ctr Bioinformat, Boston, MA 02215 USA. EM zhou@crystal.harvard.edu FU NLM NIH HHS [R01 LM008696] NR 32 TC 23 Z9 24 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD AUG PY 2007 VL 71A IS 8 BP 563 EP 575 DI 10.1002/cyto.a.20404 PG 13 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 195TH UT WOS:000248434300007 PM 17431884 ER PT J AU Jiang, S Zhou, XB Kirchhausen, T Wong, STC AF Jiang, Shan Zhou, Xiaobo Kirchhausen, Tom Wong, Stephen T. C. TI Tracking molecular particles in live cells using fuzzy rule-based system SO CYTOMETRY PART A LA English DT Article DE clathrin-coated pits; particle tracking; motion correspondence; fuzzy rule-based system ID CLATHRIN-COATED PITS; LIVING CELLS; ENDOCYTOSIS; DYNAMICS; ADAPTERS; NETWORK AB Recent development of detection techniques of molecular particles in live cells has stimulated interest in developing the new powerful techniques to track the molecular particles in live cells. One special type of cellular microscopy images is about the formation and transportation of clathrin-coated pits and vesicles. Clathrin-coated pits are very important in studying the behavior of proteins and lipids in live cells. To answer the question, whether there exist "hot spots" for the formation of Clathrin-coated pits or the pits and arrays formed randomly on the plasma membrane, it is necessary to track many hundreds of individual pits dynamically in live-cell microscope movies to capture and monitor how pits and vesicles were formed. Therefore, a motion correspondence algorithm based on fuzzy rule-based system is proposed to resolve the problem of ambiguous association encountered in these dynamic, live-cell images of clathrin assemblies. Results show that this method can accurately track most of the particles in the high volume images. (C) 2007 International Society for Analytical Cytology C1 Brigham & Womens Hosp, Funct Mol Imaging Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, HCNR Ctr Bioinformat, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02215 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 Zhou, XB (reprint author), Brigham & Womens Hosp, Funct Mol Imaging Ctr, 75 Francis St, Boston, MA 02115 USA. EM zhou@cystal.harvard.edu FU NLM NIH HHS [R01 LM008696] NR 31 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD AUG PY 2007 VL 71A IS 8 BP 576 EP 584 DI 10.1002/cyto.a.20411 PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 195TH UT WOS:000248434300008 PM 17542029 ER PT J AU Ablooglu, AJ Kang, J Handin, RI Traver, D Shattil, SJ AF Ablooglu, Ararat J. Kang, Jian Handin, Robert I. Traver, David Shattil, Sanford J. TI The zelbirafish vitronectin Receptor: Characterization of integrin alpha V and beta 3 expression patterns in early vertebrate development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE CD29; CD51; CD61; itg beta 1; itg beta 5; itg beta 8; cx43; tooth; integrin; zebrafish ID ZEBRAFISH DANIO-RERIO; EPITHELIAL-MESENCHYMAL INTERACTIONS; NEURAL CREST CELLS; TOOTH DEVELOPMENT; DIFFERENTIAL EXPRESSION; EXTRACELLULAR SEGMENT; CYTOPLASMIC DOMAIN; HUMAN ODONTOBLASTS; CRYSTAL-STRUCTURE; MOUSE EMBRYO AB alpha V beta 3 is a receptor for vitronectin and other extracellular matrix ligands, and it has been implicated in angiogenesis and osteoclast function in mammals. We have cloned full-length cDNAs of zebrafish integrin alpha V (itg alpha V), and two paralogous zebrafish beta 3 integrins (itg beta 3.1 and itg beta 3.2). Whole-mount in situ hybridization analysis revealed that alpha V and beta 3.1 share overlapping expression domains in apical ectodermal ridge, ventricular myocardium, hypothalamus, posterior tuberculum, medial tectal proliferation zone, and in the odontogenic field of the bilateral pharyngeal dentitions. In contrast to beta 3.1, beta 3.2 is transiently expressed throughout the developing embryo. In situ hybridization profiles and heterologous expression of proteins in tissue culture cells suggest that beta 3.1 is the major beta 3 paralog that associates with alpha V in zebrafish. Furthermore, when beta 3.1 expression profiles are compared to those of other potential aV partners (beta 1, beta 5, and 08), pharyngeal dentitions appear to represent a unique expression field for alpha V and beta 3.1. C1 Univ Calif San Diego, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. RP Ablooglu, AJ (reprint author), Univ Calif San Diego, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA. EM aablooglu@ucsd.edu FU NCRR NIH HHS [P40 RR012546]; NHLBI NIH HHS [HL56595]; NIAMS NIH HHS [T32AR007608] NR 62 TC 13 Z9 13 U1 0 U2 3 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 AUG PY 2007 VL 236 IS 8 BP 2268 EP 2276 DI 10.1002/dvdy.21229 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 201NH UT WOS:000248838400022 PM 17626277 ER PT J AU Boyle, S Shioda, T Perantoni, AO de Caestecker, M AF Boyle, Scott Shioda, Toshi Perantoni, Alan O. de Caestecker, Mark TI Cited1 and cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE kidney development; nephrogenesis; Cited1; Cited2; metanephric mesenchyme ID PAPILLARY THYROID-CARCINOMA; GENE-EXPRESSION; MOUSE EMBRYOGENESIS; URETERAL BUD; MICE; TRANSCRIPTION; PROTEIN; FAMILY; MORPHOGENESIS; COACTIVATOR AB Early kidney development in mammals is characterized by reciprocal tissue interaction between the ureteric bud and the metanephric mesenchyme. The coordinated response to this interaction is regulated largely at the transcriptional level. Here, we investigate the expression and function of Cited1, a transcriptional cofactor that we have previously implicated in kidney development. We show that Cited1 is expressed in the metanephric mesenchyme after invasion of the ureteric bud and that its expression is limited to the cap mesenchyme, those cells that aggregate most tightly around the tip of the ureteric bud and give rise to nephronic epithelium of the adult kidney. Cited1 is down-regulated during the initial stages of epithelial conversion and is not expressed past this progenitor stage. Despite its unique expression pattern, deletion of Cited1 does not disrupt kidney development. We hypothesized that this finding was due to functional redundancy with other members of this gene family. The expression pattern of Cited2 overlaps that of Cited1, but its deletion, either alone or in combination with Cited1, does not disrupt epithelial differentiation of the metanephric mesenchyme. From these studies, we conclude that Cited1 and 2 are dynamically expressed during kidney development, but are not required for nephrogenesis. C1 Vanderbilt Univ, Med Ctr, Div Nephrol, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA USA. Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP de Caestecker, M (reprint author), Vanderbilt Univ, Med Ctr, Div Nephrol, Dept Cell & Dev Biol, 1161 21st Ave S,S-3223,Med Ctr N, Nashville, TN 37232 USA. EM mark.de.caestecker@vanderbilt.edu FU NICHD NIH HHS [T32 HD007502]; NIDDK NIH HHS [P50 DK39261, R01 DK61558] NR 36 TC 43 Z9 44 U1 1 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 AUG PY 2007 VL 236 IS 8 BP 2321 EP 2330 DI 10.1002/dvdy.21242 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 201NH UT WOS:000248838400027 PM 17615577 ER PT J AU Rockl, KSC Hirshman, MF Brandauer, J Fujii, N Witters, LA Goodyear, LJ AF Rockl, Katja S. C. Hirshman, Michael F. Brandauer, Josef Fujii, Nobuharu Witters, Lee A. Goodyear, Laurie J. TI Skeletal muscle adaptation to exercise training - AMP-activated protein kinase mediates muscle fiber type shift SO DIABETES LA English DT Article ID GLUCOSE-TRANSPORT; MITOCHONDRIAL BIOGENESIS; BIOCHEMICAL ADAPTATIONS; ENDURANCE EXERCISE; ENZYME-ACTIVITY; CALCINEURIN; CONTRACTION; MOUSE; SLOW; METABOLISM AB Regular endurance exercise has profound benefits on overall health, including the prevention of obesity, cardiovascular disease, and diabetes. The objective of this study was to determine whether AMP-activated protein kinase (AMPK) mediates commonly observed adaptive responses to exercise training in skeletal muscle. Six weeks of voluntary wheel running induced a significant (P < 0.05) fiber type IIb to IIa/x shift in triceps muscle of wild-type mice. Despite similar wheel running capacities, this training-induced shift was reduced by similar to 40% in transgenic mice expressing a muscle-specific AMPK alpha 2 inactive subunit. Sedentary mice carrying an AMPK-activating mutation (gamma 1TG) showed a 2.6-fold increase in type IIa/x fibers but no further increase with training. To determine whether AMPK is involved in concomitant metabolic adaptations to training, we measured markers of mitochondria (citrate synthase and succinate dehydrogenase) and glucose uptake capacity (GLUT4 and hexokinase II). Mitochondrial markers increased similarly in wild-type and AMPK alpha 2-inactive mice. Sedentary gamma 1TG mice showed a similar to 25% increase in citrate synthase activity but no further increase with training. GLUT4 protein expression was not different in either line of transgenic mice compared with wild-type mice and tended to increase with training, although this increase was not statistically significant. Training induced a similar to 65% increase in hexokinase II protein in wild-type mice but not in AMPK alpha 2-inactive mice. Hexokinase II was significantly elevated in sedentary gamma 1TG mice, without an additional increase with training. AMPK is not necessary for exercise training-induced increases in mitochondrial markers, but it is essential for fiber type IIb to IIa/x transformation and increases in hexokinase II protein. C1 Joslin Diabet Ctr, Metab Sect, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Hanover, NH USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Sect, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [R01AR45670]; NIDDK NIH HHS [DK35712, DK36836, R01DK068626, T32DK07260-29] NR 52 TC 122 Z9 133 U1 1 U2 15 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2007 VL 56 IS 8 BP 2062 EP 2069 DI 10.2337/db07-0255 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 196HU UT WOS:000248473100013 PM 17513699 ER PT J AU Goel, A Chiu, H Felton, J Palmer, JP Brooks-Worrell, B AF Goel, Amit Chiu, Harvey Felton, Jamie Palmer, Jerry P. Brooks-Worrell, Barbara TI T-cell responses to islet antigens improves detection of autoimmune diabetes and identifies patients with more severe beta-cell lesions in phenotypic type 2 diabetes SO DIABETES LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; HOMEOSTASIS MODEL ASSESSMENT; ADULTS LADA; INSULIN REQUIREMENT; FOLLOW-UP; ANTIBODIES; MELLITUS; AUTOANTIBODIES; ONSET; PREDICTION AB Latent autoimmune diabetes in adults or type 1.5 diabetes is considered to be a T-cell-mediated autoimmune disease. However, identification of patients is based commonly on autoantibody (Ab) detection. To determine whether measuring T-cell reactivity to islet proteins compared with measuring Abs improves detection of autoimmune diabetes and how beta-cell function correlates with T-cell reactivity compared with Ab positivity, we assessed the T-cell proliferative responses and Ab responses (islet cell autoantibodies, insulin autoantibodies, insulinoma-associated protein-2 autoantibodies, and GAD Abs) to islet proteins of 36 phenotypic type 2 diabetic patients. To be considered Ab(+) or T-cell(+), patients were required to be positive for a minimum of two consecutive time points. beta-cell function was measured with fasting and glucagon-stimulated C-peptide. Independent of T-cell reactivity, Ab(+) and Ab(-)patients had comparable fasting and glucagon-stimulated C-peptide. Independent of Ab status, T-cell(+) patients demonstrated significantly lower glucagon-stimulated (P < 0.003) C-peptide compared with T-cell(-) patients. These data suggest that measuring T-cell responses to multiple islet proteins in phenotypic type 2 diabetic patients improves identification of patients with autoimmune diabetes and delineates those who have a more severe beta-cell lesion compared with Ab assessment alone. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Brooks-Worrell, B (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,Blvd 1,Room 609, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu FU NCRR NIH HHS [M01-RR00037]; NIDDK NIH HHS [P01-DK053004, P30-DK17047] NR 36 TC 27 Z9 30 U1 0 U2 1 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 AUG PY 2007 VL 56 IS 8 BP 2110 EP 2115 DI 10.2337/db06-0552 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 196HU UT WOS:000248473100019 PM 17473222 ER PT J AU Keenan, HA Costacou, T Sun, JK Doria, A Cavellerano, J Coney, J Orchard, TJ Aiello, LP King, GL AF Keenan, Hillary A. Costacou, Tina Sun, Jennifer K. Doria, Alessandro Cavellerano, Jerry Coney, Joseph Orchard, Trevor J. Aiello, Lloyd Paul King, George L. TI Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration - The 50-year medalist study SO DIABETES CARE LA English DT Article ID PITTSBURGH EPIDEMIOLOGY; INTENSIVE TREATMENT; PHYSICAL-ACTIVITY; FOLLOW-UP; RETINOPATHY; IDDM; PROGRESSION; PREVALENCE; MELLITUS; AGE C1 Joslin Diabet Ctr, Boston, MA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Harvard Univ, Med Sch, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP King, GL (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA USA. EM george.king@joslin.harvard.edu OI orchard, trevor/0000-0001-9552-3215 FU NEI NIH HHS [K12 EY016335]; NIDDK NIH HHS [5 P30 DK36936, T32 DK07260] NR 17 TC 56 Z9 58 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2007 VL 30 IS 8 BP 1995 EP 1997 DI 10.2337/dc06-2222 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QH UT WOS:000248570200009 PM 17507696 ER PT J AU Lipsky, BA AF Lipsky, Benjamin A. TI Diabetic foot infections: Microbiology made modern? Array of hope SO DIABETES CARE LA English DT Editorial Material ID RESISTANT STAPHYLOCOCCUS-AUREUS; DIAGNOSIS; MANAGEMENT; THERAPY C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Care Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Primary & Specialty Care Serv, 111 PCC,1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@u.washington.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 23 TC 9 Z9 9 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2007 VL 30 IS 8 BP 2171 EP 2172 DI 10.2337/dc07-0935 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QH UT WOS:000248570200046 PM 17855279 ER PT J AU Chiu, HK Tsai, EC Juneja, R Stoever, J Brooks-Worrell, B Goel, A Palmer, JP AF Chiu, Harvey K. Tsai, Elaine C. Juneja, Rattan Stoever, James Brooks-Worrell, Barbara Goel, Amit Palmer, Jerry P. TI Equivalent insulin resistance in latent autoimmune diabetes in adults (LADA) and type 2 diabetic patients SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE latent autoimmune diabetes in adults (LADA); body mass index (BMI); homeostasis model assessment (HOMA); insulin resistance; pancreatic autoantibody ID HOMEOSTASIS MODEL ASSESSMENT; ISLET-CELL ANTIBODIES; BETA-CELL; GLUCOSE; OBESITY; MELLITUS; SENSITIVITY; AUTOANTIBODIES; METABOLISM; MUSCLE AB Insulin resistance is a primary component in the pathophysiology of type 2 diabetes. In latent autoimmune diabetes in adults (LADA), insulin resistance has been reported to be significantly lower than in autoantibody-negative type 2 diabetes (T2DM), but whether this might be related to differences in body mass index (BMI) has not been excluded. Furthermore, previous studies have used limiting inclusive criteria for LADA, requiring only the presence of GADA or IA-2A. To apply more inclusive criteria for LADA, consistent with recent recommendations, we defined LADA by clinical manifestations characteristic of T2DM, but with the presence of any combination of GADA, IA-2A, ICA, or IAA. We recruited 43 LADA patients, 70 T2DM patients, and 150 non-diabetic controls. Insulin resistance was assessed by both the homeostasis model assessment and the quantitative insulin sensitivity check index, and BMI was calculated. We found that insulin resistance in LADA is equivalent to that of T2DM. When insulin resistance is assessed as a function of BMI, both diabetic populations demonstrated an insulin resistance equally greater than normal controls. The interaction between insulin resistance and BMI in the two diabetic groups was significantly different from that demonstrated in non-diabetic controls. In summary, LADA demonstrates insulin resistance of similar magnitude to T2DM, but with the concurrent component of an immune attack against the pancreatic beta-cells. LADA patients may be at significant risk for metabolic consequences of insulin resistance other than glucose metabolism, such as those described in the metabolic syndrome. As complications and treatment regimen specific to LADA are realized, improved means of identification of LADA will become increasingly important. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Chiu, HK (reprint author), Childrens Hosp & Med Ctr, 4800 Sand Point Way NE,POB 5371-MS M1-3, Seattle, WA 98105 USA. EM chiuh@u.washington.edu NR 36 TC 27 Z9 31 U1 1 U2 4 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 AUG PY 2007 VL 77 IS 2 BP 237 EP 244 DI 10.1016/j.diabres.2006.12.013 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174EM UT WOS:000246924100013 PM 17234296 ER PT J AU Gerchman, F Tong, J Utzschneider, KM Hull, RL Zraika, S Udayasankar, J McNeely, MJ Andress, DL Leonetti, DL Boyko, EJ Fujimoto, WY Kahn, SE AF Gerchman, Fernando Tong, Jenny Utzschneider, Kristina M. Hull, Rebecca L. Zraika, Sakeneh Udayasankar, Jayalakshmi McNeely, Marguerite J. Andress, Dennis L. Leonetti, Donna L. Boyko, Edward J. Fujimoto, Wilfred Y. Kahn, Steven E. TI Superiority of the Modification of Diet in Renal Disease equation over the Cockcroft-Gault equation in screening for impaired kidney function in Japanese Americans SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE MDRD; Cockcroft-Gault; creatinine clearance; glomerular filtration rate; diabetes ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; PREDICTION EQUATION; GLUCOSE-TOLERANCE; DIABETIC-PATIENTS; BODY-FAT; 2ND-GENERATION; PREVALENCE; ASIANS; CLASSIFICATION AB The Cockcroft-Gault and the Modification of Diet in Renal Disease (MDRD) Study equations have not been validated in Asian Americans with varying degrees of glucose tolerance. We compared both equations to 24-h urinary creatinine clearance, the latter as a standard measurement of glomerular filtration rate (GFR), in 398 Japanese Americans (62.1 +/- 5.8 years, mean +/- S.D.) who had normal glucose tolerance (NGT) (n = 138), impaired glucose tolerance (IGT) (n = 136) and diabetes (n = 124). Although both the Cockcroft-Gault (r = 0.65, P < 0.001) and the MDRD (r = 0.74, P < 0.001) equations correlated well with creatinine clearance, the latter was significantly superior (P = 0.013 between r values). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the MDRD equation was significantly greater than for the Cockcroft-Gault equation (AUC 0.86 versus 0.80, P = 0.015) in classifying subjects as having mildly reduced GFR (<90 ml/min per 1.73 m(2)). However, both equations overestimated the number of individuals with decreased GFR. We conclude therefore that while the MDRD equation more accurately identifies Asians who are in the early stages of kidney disease, as for other groups, a correction term appears necessary in order to reduce the number of Asian subjects being falsely diagnosed with CKD. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Div Gen Internal Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Nephrol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res Informat Ctr, Seattle, WA 98108 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NCRR NIH HHS [RR-37]; NICHD NIH HHS [R24 HD042828, R24 HD042828-10]; NIDDK NIH HHS [DK-35816, DK-02654, DK-02860, K24 DK002654, K24 DK002654-05, K24 DK002860, P30 DK035816, R01 DK055460] NR 26 TC 9 Z9 12 U1 0 U2 1 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 AUG PY 2007 VL 77 IS 2 BP 320 EP 326 DI 10.1016/j.diabres.2006.11.001 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174EM UT WOS:000246924100025 PM 17141914 ER PT J AU Barker, JM McFann, KK Orban, T AF Barker, J. M. McFann, K. K. Orban, T. CA Dpt-Study Group TI Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study SO DIABETOLOGIA LA English DT Article DE insulin autoantibodies; oral insulin; prevention; type 1 diabetes ID RISK; MELLITUS; RELATIVES AB Aims/hypothesis Our aim was to evaluate insulin autoantibody (IAA) levels over time in the Diabetes Prevention Trial Type I (DPT-1) oral insulin study to determine the effect of oral insulin compared with placebo on IAA levels. Subjects and methods The DPT-I trial randomised 372 relatives of subjects with type I diabetes, positive for IAA and with normal IVGTTs and OGTTs, to oral insulin 7.5 mg daily or placebo. Subjects were followed with IVGTTs, OGTTs and serial IAA measurements. The change in IAA level over time was modelled statistically using mixed model longitudinal data analysis with spatial exponential law for unevenly spaced data. In a separate analysis, subjects were divided into four groups by treatment and diabetes status at the end of the study. IAA levels were compared amongst the groups at randomisation, last sampling and at the maximum level. Results Longitudinal data analysis showed that treatment did not affect levels of IAA over time. After controlling for age, the IAA levels at randomisation and the last visit and the maximum values were different in the four groups. Significantly higher levels were noted in groups that developed diabetes compared with those that did not, with no significant difference by treatment group. Conclusions/interpretation This suggests that IAA levels over time were not influenced by oral insulin in subjects already positive for IAA at the start of treatment. C1 Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Barker, JM (reprint author), Barbara Davis Ctr Childhood Diabet, Box A140,Bldg M20,1775 N Ursula St,PO Box 6511, Aurora, CO 80045 USA. EM jennifer.barker@uchsc.edu FU NCRR NIH HHS [M01 RR 00069] NR 10 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2007 VL 50 IS 8 BP 1603 EP 1606 DI 10.1007/s00125-007-0694-0 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192TE UT WOS:000248225100005 PM 17583798 ER PT J AU Van den Stock, J Righart, R de Gelder, B AF Van den Stock, Jan Righart, Ruthger de Gelder, Beatrice TI Body expressions influence recognition of emotions in the face and voice SO EMOTION LA English DT Article DE emotion perception; body expression; face expression; voice prosody ID MULTISENSORY INTEGRATION; INTERMODAL PERCEPTION; FUSIFORM GYRUS; HUMAN INFANTS; BEHAVIORS; CORTEX; FEAR; SELECTIVITY; LANGUAGE; BINDING AB The most familiar emotional signals consist of faces, voices, and whole-body expressions, but so far research on emotions expressed by the whole body is sparse. The authors investigated recognition of whole-body expressions of emotion in three experiments. In the first experiment, participants performed a body expression-matching task. Results indicate good recognition of all emotions, with fear being the hardest to recognize. In the second experiment, two alternative forced choice categorizations of the facial expression of a compound face-body stimulus were strongly influenced by the bodily expression. This effect was a function of the ambiguity of the facial expression. In the third experiment, recognition of emotional tone of voice was similarly influenced by task irrelevant emotional body expressions. Taken to.-ether, the findings illustrate the importance of emotional whole-body expressions in communication either when viewed on their own or, as is often the case in realistic circumstances, in combination with facial expressions and emotional voices. C1 Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, POB 90153, NL-5000 LE Tilburg, Netherlands. EM b.degelder@uvt.nl RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 NR 42 TC 132 Z9 132 U1 2 U2 40 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD AUG PY 2007 VL 7 IS 3 BP 487 EP 494 DI 10.1037/1528-3542.7.3.487 PG 8 WC Psychology, Experimental SC Psychology GA 197DC UT WOS:000248532900003 PM 17683205 ER PT J AU Laden, F Hart, JE Smith, TJ Davis, ME Garshick, E AF Laden, Francine Hart, Jaime E. Smith, Thomas J. Davis, Mary E. Garshick, Eric TI Cause-specific mortality in the unionized US trucking industry SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE diesel; ischemic heart disease; lung cancer; mortality; occupation; traffic exposure; trucking industry ID PARTICULATE AIR-POLLUTION; DIESEL EXHAUST EXPOSURE; ST-SEGMENT DEPRESSION; LONG-TERM EXPOSURE; LUNG-CANCER; MYOCARDIAL-INFARCTION; RAILROAD WORKERS; NORWEGIAN MEN; FOLLOW-UP; FINE AB BACKGROUND: Occupational and population-based studies have related exposure to fine particulate air pollution, and specifically particulate matter from vehicle exhausts, to cardiovascular diseases and lung cancer. OBJECTIVES: We have established a large retrospective cohort to assess mortality in the unionized U.S. trucking industry. To provide insight into mortality patterns associated with job-specific exposures, we examined rates of cause-specific mortality compared with the general U.S. population. METHODS: We used records from four national trucking companies to identify 54,319 male employees employed in 1985. Cause-specific mortality was assessed through 2000 using the National Death Index. Expected numbers of all and cause-specific deaths were calculated stratifying by race, 10-year age group, and calendar period using U.S. national reference rates. Standardized mortality ratios (SMRs) and 95% confidence intervals (Cls) were calculated for the entire cohort and by job tide. RESULTS: As expected in a working population, we found a deficit in overall and all-cancer mortality, likely due to the healthy worker effect. In contrast, compared with the general U.S. population, we observed elevated rates for lung cancer, ischemic heart disease, and transport-related accidents. Lung cancer rates were elevated among all drivers (SMR = 1.10; 95% CI, 1.02-1.19) and dockworkers (SMR = 1.10; 95% CI, 0.94-1.30); ischemic heart disease was also elevated among these groups of workers [drivers, SMR = 1.49 (95% CI, 1.40-1.59); dockworkers, SMR = 1.32 (95% CI, 1.15-1.52)], as well as among shop workers (SMR = 1.34; 95% CI, 1.05-1.72). CONCLUSIONS: In this detailed assessment of specific job categories in the U.S. trucking industry, we found an excess of mortality due to lung cancer and ischemic heart disease, particularly among drivers. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Maine, Dept Resource Econ & Policy, Orono, ME USA. VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, W Roxbury, MA USA. RP Laden, F (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM Francine.Laden@channing.harvard.edu FU NCI NIH HHS [R01 CA090792, R01 CA90792] NR 54 TC 30 Z9 30 U1 0 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2007 VL 115 IS 8 BP 1192 EP 1196 DI 10.1289/ehp.10027 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 197CO UT WOS:000248531400033 PM 17687446 ER PT J AU Wang, FT Hu, H Schwartz, J Weuve, J Spiro, AS Sparrow, D Nie, HL Silverman, EK Weiss, ST Wright, RO AF Wang, Florence T. Hu, Howard Schwartz, Joel Weuve, Jennifer Spiro, Avron S., III Sparrow, David Nie, Huiling Silverman, Edwin K. Weiss, Scott T. Wright, Robert O. TI Modifying effects of the HFE polymorphisms on the association between lead burden and cognitive decline SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cognitive decline; epidemiology; HFT; lead; longitudinal studies; neuropsychologic tests ID MENTAL-STATE-EXAMINATION; HEREDITARY HEMOCHROMATOSIS; BLOOD LEAD; ALZHEIMERS-DISEASE; ELDERLY-MEN; BONE LEAD; FOLLOW-UP; PARKINSONS-DISEASE; OXIDATIVE STRESS; IRON-OVERLOAD AB BACKGROUND: As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. OBJECTIVE: Our goal was to assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. METHODS: We measured tibia and patella lead using K-X-ray fluorescence (1991-1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993-1998 and 1995-2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n = 358). RESULTS: Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele compared with men with only wild-type alleles (p interaction = 0.03), such that a 15 mu g/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (p-trend = 0.008). Results for patella lead were similar. CONCLUSION: Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Wang, FT (reprint author), i3 Drug Safety, 950 Winter St,Suite 3800, Waltham, MA 02451 USA. EM Florence.Wang@i3drugsafety.com FU NIA NIH HHS [AG18436, R01 AG014345, AG13006, R01 AG013006, AG14345, R01 AG018436]; NIAAA NIH HHS [AA08941]; NIEHS NIH HHS [R01 ES005257, ES007155, P42 ES005947, ES05257, ES05947, T32 ES007155]; PHS HHS [CCT110421] NR 62 TC 26 Z9 26 U1 1 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2007 VL 115 IS 8 BP 1210 EP 1215 DI 10.1289/ehp.9855 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 197CO UT WOS:000248531400036 PM 17687449 ER PT J AU Applebaum, KM Karagas, MR Hunter, DJ Catalano, PJ Byler, SH Morris, S Nelson, HH AF Applebaum, Katie M. Karagas, Margaret R. Hunter, David J. Catalano, Paul J. Byler, Steven H. Morris, Steve Nelson, Heather H. TI Polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in New Hampshire SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE arsenic; DNA repair polymorphism; nucleotide excision repair; skin cancer ID BASAL-CELL CARCINOMA; MULTIVARIATE CONFOUNDER SCORE; DNA-REPAIR; LUNG-CANCER; DRINKING-WATER; SODIUM ARSENITE; REACTIVATION ASSAY; XPD POLYMORPHISMS; HUMAN FIBROBLASTS; BLADDER-CANCER AB BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9-3.7]. For XPD, having variation at both loci (Asp312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic. C1 Dartmouth Coll Sch Med, Epidemiol & Biostat Sect, Dept Community & Family Med, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Missouri, Res Reactor Ctr, Columbia, MO USA. Univ Minnesota, Ctr Canc, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Karagas, MR (reprint author), Dartmouth Coll Sch Med, Epidemiol & Biostat Sect, Dept Community & Family Med, 1 Med Ctr Dr,7927 Rubin Bldg, Lebanon, NH 03756 USA. EM Margaret.R.Karagas@Dartmouth.edu RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NCI NIH HHS [R01 CA057494, R01 CA082354, R01CA082354, R01CA57494]; NIEHS NIH HHS [P42 ES007373, P42 ES07373, T32 ES007155, T32 ES07155] NR 73 TC 39 Z9 42 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2007 VL 115 IS 8 BP 1231 EP 1236 DI 10.1289/ehp.10096 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 197CO UT WOS:000248531400039 PM 17687452 ER PT J AU Jassal, DS Neilan, TG Fatima, U Holmvang, G Agnihotri, A Palacios, I Yoerger, DM AF Jassal, Davinder S. Neilan, Tomas G. Fatima, Umaima Holmvang, Godtfred Agnihotri, Arvind Palacios, Igor Yoerger, Danita M. TI Mitral valve ring dehiscence with an aorta-left atrial fistula SO EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY LA English DT Article DE mitral valve repair; mitral regurgitation; transesophageal echocardiography; cardiac magnetic resonance imaging ID DIAGNOSIS AB In an era with the increasing use of various imaging modalities including echocardiography, ventriculography and cardiac magnetic resonance (CMR) imaging, one must be aware of the limitations of each discipline. We report a case of an individual who presented with both a partial dehiscence of a mitral valve annuloplasty ring and an aorta-left atrium fistula following surgical management of infective endocarditis that was correctly identified using transesophageal echocardiographic imaging. (C) 2006 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Cardiac Catheterizat Lab, Boston, MA 02114 USA. RP Jassal, DS (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, VBK-508,55 Fruit St, Boston, MA 02114 USA. EM djassal@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1525-2167 J9 EUR J ECHOCARDIOGR JI Eur. J. Echocardiogr. PD AUG PY 2007 VL 8 IS 4 BP 296 EP 298 DI 10.1016/j.euje.2006.03.013 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 195MC UT WOS:000248415300012 PM 16697261 ER PT J AU Graham, RR Ortmann, W Rodine, P Espe, K Langefeld, C Lange, E Williams, A Beck, S Kyogoku, C Moser, K Gaffney, P Gregersen, PK Criswell, LA Harley, JB Behrens, TW AF Graham, Robert R. Ortmann, Ward Rodine, Peter Espe, Karl Langefeld, Carl Lange, Ethan Williams, Adrienne Beck, Stephanie Kyogoku, Chieko Moser, Kathy Gaffney, Patrick Gregersen, Peter K. Criswell, Lindsey A. Harley, John B. Behrens, Timothy W. TI Specific combinations of HLA-DR2 and DR3 class II haplotypes contribute graded risk for disease susceptibility and autoantibodies in human SLE SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE systemic lupus erythematosus; human leukocyte antigen; association study ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MAJOR HISTOCOMPATIBILITY COMPLEX; RO SS-A; SIB-PAIR FAMILIES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; GENERAL PEDIGREES; GENETIC-LINKAGE; CHROMOSOME 1Q41; ASSOCIATION AB The human leukocyte antigen ( HLA) Class II antigen presentation alleles DR and DQ are associated with susceptibility to systemic lupus erythematosus ( SLE) and the production of lupus-related autoantibodies. Here, we explore the effect of different combinations of Class II risk haplotypes in a large, multi-center collection of 780 SLE families. Haplotypes bearing the DRB1*1501/DQB1*0602 (DR2) and DRB1*0301/DQB1* 0201 (DR3) alleles were present in nearly two-thirds of SLE cases and were significantly associated with disease susceptibility in both family-based and case-control study designs. DR3-containing haplotypes conferred higher risk for disease than DR2, and individual homozygous for DR3 or compound heterozygous for DR3 and DR2 showed the highest risk profile. DR2 haplotypes were also found to be associated with antibodies to the nuclear antigen Sm, and, as previously observed, DR3 genotypes were associated with Ro and La autoantibodies. Interestingly, SLE cases and unaffected family members who were DR2/DR3 compound heterozygotes showed particularly strong risk of developing antibodies to Ro, and were enriched for La and Sm. These data provide convincing evidence that particular combinations of HLA Class II DR2 and DR3 haplotypes are key determinants of autoantibody production and disease susceptibility in human SLE. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Mol Biol, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Dept Rheumatol, Minneapolis, MN 55455 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Robert S Boas ctr Genom & Human Genet, Manhasset, NY USA. Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Med, Oklahoma City, OK USA. RP Behrens, TW (reprint author), Genentech Inc, Exploratory Clin Dev, 1 DNA Way, San Francisco, CA 94080 USA. EM behrens.tim@gene.com RI Beck-Roth, Stephanie/B-8167-2009 FU NCRR NIH HHS [5 M01 RR00079, RR024013]; NIAID NIH HHS [AI24717, AI32584]; NIAMS NIH HHS [AR42460, AR048094, AR048940, AR12253, P60 AR053308] NR 54 TC 67 Z9 71 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD AUG PY 2007 VL 15 IS 8 BP 823 EP 830 DI 10.1038/sj.ejhg.5201827 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 194PQ UT WOS:000248356700002 PM 17406641 ER PT J AU Tang, Y Epstein, MP Anderson, GM Zabetian, CP Cubells, JF AF Tang, Yi-lang Epstein, Michael P. Anderson, George M. Zabetian, Cyrus P. Cubells, Joseph F. TI Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE dopamine beta-hydroxylase; African American; linkage disequilibrium; genetic association; haplotype ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SINGLE NUCLEOTIDE POLYMORPHISM; LINKAGE DISEQUILIBRIUM; CEREBROSPINAL-FLUID; LOCUS; INDIVIDUALS; HEALTHY AB Several variants at DBH are significantly associated with plasma DbH activity (pDbH). However, the overwhelming majority of data on this genotype-phenotype relationship has been gathered in samples from Europeans and European Americans (EAs). In this study, we examined the relationship between DBH polymorphisms and pDbH in samples from African-American (AA) subjects. Genotypes were determined at a 19-bp insertion/deletion polymorphism (ins/del) and four single-nucleotide polymorphisms (SNPs) at DBH in 109 samples. Analyses were performed using analyses of variance (ANOVAs) ( for individual SNPs) and regression procedures (to assess the joint effects and the specific SNP-based haplotypes). We found: (1) single-variant analysis of all polymorphisms revealed apparent associations to pDbH, with rs1611115 accounting for the largest proportion of the variance in pDbH (28.7%) and ins/del the smallest (6.5%); ( 2) modest but significant linkage disequilibrium (LD) existed between ins/del and rs1611115; (3) LD between all other pairs of variants was not observed; (3) stepwise regression showed that a model containing rs1611115, rs2519152 and rs6271 accounted for 37.6% of the variance in pDbH, with rs6271 showing additional 7.6% above the effect of rs1611115, and rs2519152 showing additional 2% above rs1611115 and rs6271; (4) two common haplotypes, C-T-C and T-C-C at rs1611115-rs2519152-rs6271 were significantly associated with pDbH (P = 0.0025 and 0.0036, respectively). The data support the validity of prior reported associations and underscore the importance of analyzing multiple SNPs across DBH in future association studies examining disease and biochemical phenotypes. C1 Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Behav Sci, Atlanta, GA 30322 USA. Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Dept Psychiat, New Haven, CT 06520 USA. Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. Univ Washington, Sch Med, Geriatr Res Educ & Clin Ctr, Dept Neurol,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Cubells, JF (reprint author), Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Suite 301, Atlanta, GA 30322 USA. EM jcubells@genetics.emory.edu FU NIDA NIH HHS [R01 DA12422, K02DA015766]; NINDS NIH HHS [K08 NS044138] NR 27 TC 27 Z9 30 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD AUG PY 2007 VL 15 IS 8 BP 878 EP 883 DI 10.1038/sj.ejhg.5207838 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 194PQ UT WOS:000248356700010 PM 17457369 ER PT J AU Weisberg, R Fava, M Hartford, J Erickson, J D'Souza, D Lledo, A Russell, J AF Weisberg, R. Fava, M. Hartford, J. Erickson, J. D'Souza, D. Lledo, A. Russell, J. TI Efficacy of duloxetine in the treatment of generalized anxiety disorder in patients with clinically significant painful physical symptoms SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 11th Congress of the European-Federation-of-Neurological-Societies CY AUG 25-28, 2007 CL Brussels, BELGIUM SP European Federat Neurol Soc C1 [Weisberg, R.] Brown Univ, Dept Biol Med, Providence, RI USA. [Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fava, M.] Harvard Med Sch, Boston, MA USA. [Hartford, J.] Hartford Res Grp, Florence, KY USA. [Erickson, J.; D'Souza, D.; Russell, J.] Lilly Res Labs, Indianapolis, IN USA. [Lledo, A.] Eli Lilly & Co, Lilly Res Ctr Ltd, Windlesham, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD AUG PY 2007 VL 14 SU 1 BP 138 EP 138 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225LL UT WOS:000250519300450 ER PT J AU Woolf, CJ AF Woolf, C. J. TI Exploring mechanisms of neuropathic pain SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 11th Congress of the European-Federation-of-Neurological-Societies CY AUG 25-28, 2007 CL Brussels, BELGIUM SP European Federat Neurol Soc C1 [Woolf, C. J.] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD AUG PY 2007 VL 14 SU 1 BP 322 EP 322 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225LL UT WOS:000250519301052 ER PT J AU Woolf, CJ Dickenson, AH Taylor, CP Tolle, TR AF Woolf, C. J. Dickenson, A. H. Taylor, C. P. Toelle, T. R. TI alpha(2)-delta and chronic disorders - A journey of exploration SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 11th Congress of the European-Federation-of-Neurological-Societies CY AUG 25-28, 2007 CL Brussels, BELGIUM SP European Federat Neurol Soc ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PREGABALIN; SUBUNIT; TARGET; PAIN; PROTEIN C1 [Woolf, C. J.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Dickenson, A. H.] UCL, Dept Pharmacol, London WC1E 6BT, England. [Taylor, C. P.] Pfizer Global Res & Dev, Dept CNS Biol, Ann Arbor, MI USA. [Toelle, T. R.] Tech Univ Munich, Dept Neurol, D-8000 Munich, Germany. NR 13 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD AUG PY 2007 VL 14 SU 1 BP 323 EP 323 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225LL UT WOS:000250519301055 ER PT J AU Herndon, JH Hwang, R Bozic, KJ AF Herndon, James H. Hwang, Raymond Bozic, K. J. TI Healthcare technology and technology assessment SO EUROPEAN SPINE JOURNAL LA English DT Article DE technology; assessment; costs; clinical trials ID CLINICAL-TRIALS; ADVERSE EVENTS; REPLACEMENT; SURGERY AB New technology is one of the primary drivers for increased healthcare costs in the United States. Both physician and industry play important roles in the development, adoption, utilization and choice of new technologies. The Federal Drug Administration regulates new drugs and new medical devices, but healthcare technology assessment remains limited. Healthcare technology assessment originated in federal agencies; today it is decentralized with increasing private sector efforts. Innovation is left to free market forces, including direct to consumer marketing and consumer choice. But to be fair to the consumer, he/she must have free knowledge of all the risks and benefits of a new technology in order to make an informed choice. Physicians, institutions and industry need to work together by providing proven, safe, clinically effective and cost effective new technologies, which require valid pre-market clinical trials and post-market continued surveillance with national and international registries allowing full transparency of new products to the consumer-the patient. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA USA. Univ Calif San Francisco, Sch Med, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA USA. EM jherndon@partners.org NR 37 TC 9 Z9 9 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD AUG PY 2007 VL 16 IS 8 BP 1293 EP 1302 DI 10.1007/s00586-007-0369-z PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 201LW UT WOS:000248834000026 PM 17426985 ER PT J AU Herndon, JH Hwang, R Bozic, KJ AF Herndon, James H. Hwang, Raymond Bozic, K. J. TI Healthcare technology and technology assessment (vol 16, pg 1293, 2007) SO EUROPEAN SPINE JOURNAL LA English DT Correction C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA USA. Univ Calif San Francisco, Sch Med, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA USA. EM jherndon@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD AUG PY 2007 VL 16 IS 8 BP 1303 EP 1303 DI 10.1007/s00586-007-0441-8 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 201LW UT WOS:000248834000027 ER PT J AU Greenzang, C Manoach, DS Goff, DC Barton, JJS AF Greenzang, Cathleen Manoach, Dara S. Goff, Donald C. Barton, Jason J. S. TI Task-switching in schizophrenia: active switching costs and passive carry-over effects in an antisaccade paradigm SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE task switch; schizophrenia; antisaccades; reconfiguration; executive function ID SORTING TEST; SET RECONFIGURATION; EYE-MOVEMENTS; PERFORMANCE; INHIBITION; PERSEVERATION; ACTIVATION; PLASTICITY; SACCADES; DEFICITS AB It has been hypothesized that impaired task-switching underlies some of the behavioural deficits in schizophrenia. However, task-switching involves many cognitive operations. In this study our goal was to isolate the effects on latency and accuracy that can be attributed to specific task-switch processes, by studying the inter-trial effects in blocks of randomly mixed prosaccades and antisaccades. By varying the preparatory interval between an instructional cue and the target, we assessed the costs of both (1) an active reconfiguration process that was triggered by the cue, and (2) passive carry-over effects persisting from the prior trial. We tested 15 schizophrenic subjects and 14 matched controls. A very short preparatory interval increased error rates and saccadic latencies in both groups, but more so in schizophrenia, suggesting difficulty in rapidly activating saccadic goals. However, the contrast between repeated and switched trials showed that the costs of task switching in schizophrenia were not significantly different from the controls, at either short or long preparatory intervals, for both antisaccades and prosaccades. These results confirm prior observations that passive carry-over effects are normal in schizophrenia, and show that active reconfiguration is also normal in this disorder. Thus problems with executive control in schizophrenia may not affect specific task-switching operations. C1 VGH Eye Care Ctr, Neuroophthalmol Sect D, Vancouver, BC V5Z 3N9, Canada. Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harverd Coll, Dept Neurobiol, Cambridge, MA USA. RP Barton, JJS (reprint author), VGH Eye Care Ctr, Neuroophthalmol Sect D, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada. EM jasonbarton@shaw.ca RI Barton, Jason/A-6362-2012 FU NIMH NIH HHS [1R01 MH67720] NR 52 TC 9 Z9 9 U1 6 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD AUG PY 2007 VL 181 IS 3 BP 493 EP 502 DI 10.1007/s00221-007-0946-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 191FL UT WOS:000248115900009 PM 17486327 ER PT J AU Akilov, OE Kosaka, S O'Riordan, K Hasan, T AF Akilov, Oleg E. Kosaka, Sachiko O'Riordan, Katie Hasan, Tayyaba TI Parasiticidal effect of delta-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE photodynamic therapy; cutaneous leishmaniasis; Leishmania major; aminolevulinic acid ID INTRACELLULAR STAGES; PROTOPORPHYRIN-IX; DIFFERENTIATION; AMAZONENSIS; EFFICACY; PHOTOSENSITIZER; PROMASTIGOTES; BIOSYNTHESIS; INACTIVATION; MACROPHAGES AB Several clinical reports have shown promising, but not optimal, results from photodynamic therapy with delta-aminolevulinic acid-derived protoporphyrin IX, termed ALA-PDT, as a treatment for cutaneous leishmaniasis (CL). Therefore, understanding the basis of the phototoxic response of Leishmania parasites to ALA-PDT may be critical for optimization. We report here both in vitro and in vivo mechanistic studies of ALA-PDT against CL. Following in vitro co-incubation of Leishmania major with 0.1 mu m ALA, the PpIX concentration remained at the basal level, whereas after co-incubation with 0.1 mu m exogenous PpIX, the PpIX level was 100-fold higher. No differences in ALA-derived PpIX levels were detected between Leishmania-infected and non-infected J774.2 cells, and PDT did not demonstrate any parasiticidal effects on amastigotes. In contrast, in vivo topical ALA-PDT, performed on a murine CL model, resulted in significant reductions of the parasite loads and vigorous tissue destruction. After ALA-PDT, a dramatically decreased percentage of macrophages and increased levels of interleukin-6 were observed in the infected skin. The clinical outcome observed with ALA-PDT is likely the result of unspecific tissue destruction accompanied by depopulation of macrophages rather than direct killing of parasites. C1 Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Med Sch,Wellman Ctr Photomed, Boston, MA 02114 USA. RP Akilov, OE (reprint author), Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Med Sch,Wellman Ctr Photomed, 40 Blossom St,BAR 314, Boston, MA 02114 USA. EM thasan@partners.org NR 35 TC 50 Z9 53 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD AUG PY 2007 VL 16 IS 8 BP 651 EP 660 DI 10.1111/j.1600-0625.2007.00578.x PG 10 WC Dermatology SC Dermatology GA 186ZR UT WOS:000247817600005 PM 17620092 ER PT J AU Ramaiah, SK Rittling, S AF Ramaiah, Shashi K. Rittling, Susan TI Role of osteopontin in regulating hepatic inflammatory responses and toxic liver injury SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE hepatic injury; inflammation; liver toxicity; neutrophils; osteopontin ID ALCOHOLIC HEPATITIS; KUPFFER CELLS; RAT-LIVER; STRUCTURAL REQUIREMENTS; NEUTROPHIL INFILTRATION; HEPATOCELLULAR INJURY; MACROPHAGE-MIGRATION; FULMINANT-HEPATITIS; BONE SIALOPROTEIN; DEFICIENT MICE AB Osteopontin (OPN) produced by cells of the immune system, epithelial tissue, smooth muscle cells, osteciblasts and tumor cells has been implicated in various pathophysiological functions such as cell binding, spreading and migration, and tumor metastasis. OPN is known to bind to integrins expressed on macrophages through the arginine-glycine-aspartic acid (RGD) motif and promote migration of cells resulting in granuloma. In the liver, it has been reported that hepatic Kupffer cells secrete OPN facilitating macrophage infiltration in necrotic areas following carbon tetrachloride liver toxicity. Recent work has underlined the importance of OPN as a pivotal cytokine/chemokine in the generated hepatic neutrophil response during early phase alcoholic liver injury. Increased hepatobiliary OPN expression correlated well with higher neutrophil infiltration in a rat model of alcoholic steato hepatitis. In the same model of alcoholic steatohepatitis, higher hepatic expression of OPN in females was attributed to the higher neutrophil infiltration and consequent higher female sensitivity to liver damage. OPN as a potential biomarker for inflammatory liver disease has also been recently assessed. This review will focus on studies demonstrating the role of OPN in mediating hepatic inflammation (neutrophils, monocytes/macrophages and lymphocytes) and the ensuing liver toxicity. C1 Texas A&M Univ, Dept Pathobiol, Coll Vet Med, College Stn, TX 77843 USA. Forsyth Inst, Boston, MA 02115 USA. RP Ramaiah, SK (reprint author), Texas A&M Univ, Dept Pathobiol, Coll Vet Med, MS-4467, College Stn, TX 77843 USA. EM srarriaiah@cvm.tamu.edu FU NIAAA NIH HHS [AA016316]; NIDDK NIH HHS [R01-DK067685] NR 54 TC 32 Z9 32 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD AUG PY 2007 VL 3 IS 4 BP 519 EP 526 DI 10.1517/17425225.3.4.519 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 206QS UT WOS:000249198600004 PM 17696803 ER PT J AU Gutierrez-Fernandez, A Inada, M Balbin, M Fueyo, A Pitiot, AS Astudillo, A Hirose, K Hirata, M Shapiro, SD Noel, A Werb, Z Krane, SM Lopez-Otin, C Puente, XS AF Gutierrez-Fernandez, Ana Inada, Masaki Balbin, Milagros Fueyo, Antonio Pitiot, Ana S. Astudillo, Aurora Hirose, Kenji Hirata, Michiko Shapiro, Steven D. Noel, Agnes Werb, Zena Krane, Stephen M. Lopez-Otin, Carlos Puente, Xose S. TI Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8) SO FASEB JOURNAL LA English DT Article DE neutrophil; MMP-9; cancer; protease; degradome ID MATRIX-METALLOPROTEINASE; KERATINOCYTE MIGRATION; NEUTROPHIL GELATINASE; RESISTANT MOUSE; EXPRESSION; CELLS; CANCER; GROWTH; TISSUE; REGENERATION AB Matrix metalloproteinases (MMPs) have been implicated in numerous tissue-remodeling processes. The finding that mice deficient in collagenase-2 (MMP-8) are more susceptible to develop skin cancer, prompted us to investigate the role of this protease in cutaneous wound healing. We have observed a significant delay in wound closure in MMP8(-/-) mice and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points. These changes were accompanied by alterations in the TGF-beta 1 signaling pathway and by an apoptosis defect in MMP8(-/-) mice. The delay in wound healing observed in MMP8(-/-) mice was rescued by bone marrow transplantation from wildtype mice. Analysis of other MMPs showed that MMP8(-/-) mice had a significant increase in the expression of MMP-9, suggesting that both proteases might act coordinately in this process. This possibility was further supported by the novel finding that MMP-8 and MMP-9 form specific complexes in vivo. Taken together, these data indicate that MMP-8 participates in wound repair by contributing to the resolution of inflammation and open the possibility to develop new strategies for treating wound healing defects. C1 Univ Oviedo, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. Univ Oviedo, Fac Med, Inst Univ Oncol, E-33006 Oviedo, Spain. Univ Oviedo, Hosp Cent Asturias, Serv Oncol Mol, E-33080 Oviedo, Spain. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Pulm & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Liege, Lab Tumor & Dev Biol, Liege, Belgium. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RP Puente, XS (reprint author), Univ Oviedo, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. EM xspuente@uniovi.es RI Hirata, Michiko/D-2351-2013; inada, masaki/D-1581-2013; Balbin, Milagros/I-4206-2015; Lopez-Otin, Carlos/C-6657-2013; OI Hirata, Michiko/0000-0002-5291-6112; inada, masaki/0000-0002-5066-8506; Lopez-Otin, Carlos/0000-0001-6964-1904; Fueyo-Silva, Antonio/0000-0002-7121-9398; Noel, Agnes/0000-0002-7670-6179; Suarez-Puente, Xose/0000-0001-9525-1483; Gutierrez-Fernandez, Ana/0000-0002-9287-8843 FU NCI NIH HHS [CA105379, CA072006, P01 CA072006, P01 CA072006-10, U01 CA105379, U01 CA105379-05]; NIAMS NIH HHS [AR044815, R01 AR044815, R01 AR044815-10] NR 51 TC 120 Z9 122 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2007 VL 21 IS 10 BP 2580 EP 2591 DI 10.1096/fj.06-7860com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 196AS UT WOS:000248454400031 PM 17392479 ER PT J AU Crouch, PJ White, AR Bush, AI AF Crouch, Peter J. White, Anthony R. Bush, Ashley I. TI The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimer's disease SO FEBS JOURNAL LA English DT Review DE Alzheimer's disease; amyloid-beta; biometals; copper; iron; oxidative stress; tau; zinc ID AMYLOID-BETA-PEPTIDE; CYTOCHROME-C-OXIDASE; COPPER-DEPENDENT INHIBITION; LONG-TERM POTENTIATION; AGE-RELATED-CHANGES; A-BETA; SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; ABNORMAL PHOSPHORYLATION; PRECURSOR PROTEIN AB The postmortem Alzheimer's disease brain is characterized histochemically by the presence of extracellular amyloid plaques and neurofibrillary tangles. Also consistent with the disease is evidence for chronic oxidative damage within the brain. Considerable research data indicates that these three critical aspects of Alzheimer's disease are interdependent, raising the possibility that they share some commonality with respect to the ever elusive initial factor(s) that triggers the development of Alzheimer's disease. Here, we discuss reports that show a loss of metal homeostasis is also an important event in Alzheimer's disease, and we identify how metal dyshomeostasis may contribute to development of the amyloid-beta, tau and oxidative stress biology of Alzheimer's disease. We propose that therapeutic agents designed to modulate metal bio-availability have the potential to ameliorate several of the dysfunctional events characteristic of Alzheimer's disease. Metal-based therapeutics have already provided promising results for the treatment of Alzheimer's disease, and new generations of pharmaceuticals are being developed. In this review, we focus on copper dyshomeostasis in Alzheimer's disease, but we also discuss zinc and iron. C1 Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Melbourne, Ctr Neurosci, Parkville, Vic 3052, Australia. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Bush, AI (reprint author), Mental Hlth Res Inst Victoria, 155 Oak St, Parkville, Vic 3052, Australia. EM abush@mhri.edu.au RI Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016 OI Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891 NR 88 TC 53 Z9 53 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD AUG PY 2007 VL 274 IS 15 BP 3775 EP 3783 DI 10.1111/j.1742-4658.2007.05918.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 199UG UT WOS:000248720100004 PM 17617225 ER PT J AU Kulich, SM Horbinski, C Patel, M Chu, CT AF Kulich, Scott M. Horbinski, Craig Patel, Manisha Chu, Charleen T. TI 6-Hydroxydopamine induces mitochondrial ERK activation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE mitochondria; reactive oxygen species; Parkinson's disease; extracellular signal-regulated MAP kinases; 6-hydroxydopamine ID REGULATED KINASE ACTIVATION; EPIDERMAL-GROWTH-FACTOR; PARKINSONS-DISEASE; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; PC12 CELLS; COMPLEX-I; DOPAMINERGIC-NEURONS; ENDOTHELIAL-CELLS; OXIDATIVE STRESS AB Reactive oxygen species (ROS) are implicated in 6-hydroxydopamine (6-OHDA) injury to catecholammergic neurons; however, the mechanism(s) are unclear. In addition to ROS generated during autoxidation, 6-OHDA may initiate secondary cellular sources of ROS that contribute to toxicity. Using a neuronal cell line, we found that catalytic metalloporphyrin antioxidants conferred protection if added 1 h after exposure to 6-OHDA, whereas the hydrogen peroxide scavenger catalase failed to protect if added more than 15 min after 6-OHDA. There was a temporal correspondence between loss of protection and loss of the ability of the antioxidant to inhibit 6-OHDA-induced ERK phosphorylation. Time course studies of aconitase inactivation, an indicator of intracellular superoxide, and MitoSOX red, a mitochondria targeted ROS indicator, demonstrate early intracellular ROS followed by a delayed phase of mitochondrial ROS production, associated with phosphorylation of a mitochondrial pool of ERK. Furthermore, on initiation of mitochondrial ROS and ERK activation, 6-OHDA-injured cells became refractory to rescue by metalloporphyrin antioxidants. Together with previous studies showing that inhibition of the ERK pathway confers protection from 6-OHDA toxicity, and that phosphorylated ERK accumulates in mitochondria of degenerating human Parkinson's disease neurons, these studies implicate mitochondrial ERK activation in Parkinsonian oxidative neuronal injury. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Pathol, Div Neuropathol, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Dept Pathol, Pittsburgh, PA 15240 USA. Univ Colorado, Dept Pharmaceut Sci, Denver, CO 80262 USA. RP Kulich, SM (reprint author), Univ Pittsburgh, Sch Med, Dept Pathol, Div Neuropathol, 200 Lothrop St, Pittsburgh, PA 15261 USA. EM kulichsm@upmc.edu; ctc4@pitt.edu RI Chu, Charleen/B-1601-2008 OI Chu, Charleen/0000-0002-5052-8271 FU NIA NIH HHS [R01 AG026389, R01 AG026389-01A2, AG026389]; NINDS NIH HHS [NS045748, NS053777, NS40817, R01 NS040817, R01 NS040817-04, R01 NS045748, R01 NS045748-04, R21 NS053777, R21 NS053777-02] NR 81 TC 65 Z9 66 U1 1 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 AUG 1 PY 2007 VL 43 IS 3 BP 372 EP 383 DI 10.1016/j.freeradbiomed.2007.04.028 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 190WH UT WOS:000248090800007 PM 17602953 ER PT J AU Valente, AJ El Jamali, A Epperson, TK Gamez, MJ Pearson, DW Clark, RA AF Valente, Anthony J. El Jamali, Amina Epperson, Terry Kay Gamez, Maria J. Pearson, Doran W. Clark, Robert A. TI NOX1 NADPH oxidase regulation by the NOXA1 SH3 domain SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE NADPH oxidase; NOX1; NOXA1; SH3 domain; superoxide ID SUPEROXIDE-GENERATING OXIDASE; TISSUE EXPRESSION; NAD(P)H OXIDASE; MESSENGER-RNA; ACTIVATION; PROTEINS; CELLS; P67(PHOX); P47(PHOX); HOMOLOGY AB We investigated the role of the single SH3 domain of NOXA I in NOX I NADPH oxidase function using wild-type and mutated NOXA I and the products of two variant NOXA1 transcripts isolated from CaCo2 cells by reverse transcription polymerase chain reaction. The first variant, NOXA1(trunc), contained a number of point mutations, including A51T, T261A, and a nonsense mutation at position 274. On transfection into K562 cells stably expressing NOX1 and NOXO1, both NOXA1(trunc), and an equivalent truncated wild-type NOXAI(1-273) were expressed as similar to 29-kDa truncated NOXA I proteins lacking both PB I and SH3 domains, yet both were as active as wild-type NOXA I in phorbol-stimulated superoxide generation. Kinetic analysis demonstrated that truncated NOXAI activated the NOX1 system at an accelerated rate compared with NOXAL Deletion studies showed that the slower kinetics of wild-type NOXA I depended primarily on its SH3 domain, suggesting SH3 -dependent delay in forming the active NOX1/NOXO1/NOXA1 complex. The second variant, NOXA1(inhib), encoded a protein lacking the activation domain due to absence of exons 5 and 6 but including a heptapeptide (EPDVPLA) SH3 domain insertion resulting from alternative splicing in exon 14. NOXA1(inhib) failed to support superoxide-generating activity and exhibited transdominant inhibition of NOXA1. Insertion of the heptapeptide into the corresponding site in wild-type NOXAI inhibited its activity by similar to 90%, rendered it a transdominant inhibitor of wild-type NOXAI, and abrogated binding of its SH3 domain to NOXO1 and p47(phox). These studies demonstrate that, in reconstituted NOX1/NOXO1/NOXA1 systems, the NOXA I SH3 domain is not required for function but, when present, can critically modulate the activity of the enzyme system. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Valente, AJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM valente@uthscsa.edu FU NIA NIH HHS [R01 AG019519, AG19519]; NIAID NIH HHS [R01 AI020866]; PHS HHS [A120866] NR 34 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2007 VL 43 IS 3 BP 384 EP 396 DI 10.1016/j.freeradbiomed.2007.04.022 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 190WH UT WOS:000248090800008 PM 17602954 ER PT J AU Yu, L Ioannou, GN AF Yu, Lei Ioannou, George N. TI Survival of liver transplant recipients with hemochromatosis in the United States SO GASTROENTEROLOGY LA English DT Article ID HEPATIC IRON OVERLOAD; HEREDITARY HEMOCHROMATOSIS; GRAFT-SURVIVAL; CIRRHOSIS; PATIENT AB Background & Aims: Earlier studies have suggested that patients with hemochromatosis have poor post-transplantation survival. We aimed to compare patients with hemochromatosis to those with other causes of liver disease with regard to post-transplantation survival. Methods: We compared the post-transplant survival of patients with and without hemochromatosis using data provided by the United Network for Organ Sharing on 50,306 adult, cadaveric liver transplantations performed in the United States between January 1, 1990, and July 18, 2006. Results: During 1990-1996, the post-transplantation survival of patients with hemochromatosis (n = 177) at I year (79.1%), 3 years (71.8%), and 5 years (64.6%) was lower than the average 1-year (86.4%), 3-year (79.S%), and 5-year (73.8%) survival of all other transplant recipients (hazard ratio for death, 1.38; 95% confidence interval [CI], 1.12-1.71). In contrast, during 1997-2006, patients with hemochromatosis (n = 217) had excellent 1-year (86.1%), 3-year (80.8%), and S-year (77.3%) post-transplantation survival, which was not different from the 1-year (88.4%), 3-year (80.3%), and 5-year (74.0%) post-transplantation survival of all other transplant recipients (hazard ratio for death, 0.89; 95% CI, 0.65-1.22). Adjustment for donor and recipient characteristics did not substantially change these results. Compared with recipients without hemochromatosis, those with hemochromatosis were more likely to die of cardiovascular diseases and less likely to die as a result of graft failure. Conclusions: The post-transplantation survival of patients with hemochromatosis, which was previously reported to be poor, has been excellent in the United States during the past 10 years. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, S-111-Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu NR 17 TC 27 Z9 27 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 AUG PY 2007 VL 133 IS 2 BP 489 EP 495 DI 10.1053/j.gastro.2007.05.054 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 197VW UT WOS:000248585600019 PM 17681170 ER PT J AU Kim, BM Mao, JH Taketo, MM Shivdasani, RA AF Kim, Byeong-Moo Mao, Junhao Taketo, Makoto M. Shivdasani, Ramesh A. TI Phases of canonical Wnt signaling during the development of mouse intestinal epithelium SO GASTROENTEROLOGY LA English DT Article ID BETA-CATENIN; GASTROINTESTINAL-TRACT; COLORECTAL-CANCER; COLON-CARCINOMA; STEM-CELL; MICE; MORPHOGENESIS; EXPRESSION; APC; DIFFERENTIATION AB Background & Aims: Intestinal crypts constitute a niche in which epithelial progenitors respond to Wnt signals, replicate, and prepare to differentiate. Because mutations in Wnt pathway genes lead to intestinal cancer, the role of Wnt signaling in gut epithelial homeostasis is a subject of intense investigation. We studied how Wnt signaling is established during intestine development. Methods: We studied spatiotemporal features of Writ signaling at formative stages in mouse embryos, when villous projections appear and crypt precursors occupy intervillus regions. We used TOP-GAL transgenic and Axin2(LacZ) mice, which report faithfully on canonical Wnt activity, relevant molecular markers, and embryos with aberrant beta-catenin activation. Results: Developing intestines first display evidence for Writ signaling after appearance of villi. During villus morphogenesis, intervillus cells proliferate actively but lack signs of canonical Writ signaling. Surprisingly, in late gestation and briefly thereafter, conspicuous Wnt activity is evident in differentiated, postmitotic villus epithelium. Neither Tcf4, a principal transcriptional effector of intestinal Writ signals, nor candidate Wnt targets CD44 and cyclinD1 are expressed in late fetal villus cells that show high Writ activity. Instead, those cells express the related factor Tcf3 and a different Wnt target, c-Myc. Premature and deregulated beta-catenin activation causes severe villus dysmorphogenesis in transgenic mice. Conclusions: Relationships among Writ signaling, epithelial proliferation, and tissue differentiation are reversed in the developing and adult gut. The canonical Wnt pathway has independent, albeit possibly overlapping, functions in early intestinal villi and adult crypts. These observations advance understanding of Writ functions in intestinal development and disease. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dept Med, Boston, MA USA. Harvard Univ, Dept Mol & Cell Biol, Boston, MA USA. Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto, Japan. Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto, Japan. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIDDK NIH HHS [R01DK61139] NR 42 TC 54 Z9 55 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 AUG PY 2007 VL 133 IS 2 BP 529 EP 538 DI 10.1053/j.gastro.2007.04.072 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 197VW UT WOS:000248585600023 PM 17681174 ER PT J AU Maillard, MH Snapper, SB AF Maillard, Michel H. Snapper, Scott B. TI Teaching tolerance with a probiotic antigen delivery system SO GASTROENTEROLOGY LA English DT Article ID REGULATORY T-CELLS; MYELIN BASIC-PROTEIN; LACTIC-ACID BACTERIA; ORAL TOLERANCE; TGF-BETA; IMMUNE-RESPONSES; DENDRITIC CELLS; COLITIS; DISEASE; MICE C1 Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med,Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med,Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Snapper, SB (reprint author), Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med,Gastrointestinal Unit, 55 Blossom St, Boston, MA 02114 USA. EM ssnapper@hms.harvard.edu NR 38 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2007 VL 133 IS 2 BP 706 EP 709 DI 10.1053/j.gastro.2007.06.055 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 197VW UT WOS:000248585600037 PM 17681187 ER PT J AU Hume, CR Bratt, DL Oesterle, EC AF Hume, Clifford R. Bratt, Debra Lee Oesterle, Elizabeth C. TI Expression of LHX3 and SOX2 during mouse inner ear development SO GENE EXPRESSION PATTERNS LA English DT Article DE LHX; LIM-homeodomain; MATH-1; inner ear; cochlea; ATOH1; SOX; Hmg box; hair cell; deafness; HLH; bHLH; genetics; hearing ID HAIR-CELLS; UNCONVENTIONAL MYOSINS; MOTOR-NEURONS; FATE DETERMINATION; SENSORY EPITHELIA; STEM-CELLS; IN-VIVO; MATH1; ORGAN; GENE AB A cascade of transcription factors is believed to regulate the coordinate differentiation of primordial inner ear cells into the subtypes of hair cells and supporting cells. While candidate genes involved in this process have been identified, the temporal and spatial patterns of expression of many of these have not been carefully described during the extended period of inner ear development and functional maturation. We systematically examined the expression of two such transcription factors, LHX3 and SOX2, from the time of hair cell terminal mitoses into adulthood. We show that LHX3 is expressed specifically in auditory and vestibular hair cells soon after terminal mitoses and persists into the adult in vestibular hair cells. While SOX2 expression is widespread in the inner ear sensory epithelia prior to hair cell differentiation, it has a unique pattern of expression in the mature auditory and vestibular organs. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Virginia Merrill Bloedel Hearing Res Ctr, VMBHRC,CHDD, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Hume, CR (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Virginia Merrill Bloedel Hearing Res Ctr, VMBHRC,CHDD, CD176,Box 357923,1959 NE Pacific, Seattle, WA 98195 USA. EM hume@u.washington.edu FU NICHD NIH HHS [P30 HD-02774]; NIDCD NIH HHS [K08 DC006437-04, DC-006437, R01 DC003944, P30 DC004661, DC-03944, P30 DC-04661, K08 DC006437] NR 53 TC 76 Z9 77 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD AUG PY 2007 VL 7 IS 7 BP 798 EP 807 DI 10.1016/j.modgep.2007.05.002 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 208PF UT WOS:000249331000011 PM 17604700 ER PT J AU Gevry, N Chan, HM Laflamme, L Livingston, DM Gaudreau, L AF Gevry, Nicolas Chan, Ho Man Laflamme, Liette Livingston, David M. Gaudreau, Luc TI p21 transcription is regulated by differential localization of histone H2A.Z SO GENES & DEVELOPMENT LA English DT Article DE H2A.Z; Myc; p21; p400; p53 ID CHROMATIN REMODELING COMPLEX; RNA-POLYMERASE-II; VARIANT H2A.Z; TUMOR SUPPRESSION; P53 PATHWAY; DNA-DAMAGE; SENESCENCE; ACETYLTRANSFERASE; PROTEIN; P400 AB In yeast cells, H2A.Z regulates transcription and is globally associated within a few nucleosomes of the initiator regions of numerous promoters. H2A.Z is deposited at these loci by an ATP-dependent complex, Swr1.com. Here we show that H2A.Z suppresses the p53 -> p21 transcription and senescence responses. Upon DNA damage, H2A.Z is first evicted from the p21 promoter, followed by the recruitment of the Tip60 histone acetyltransferase to activate p21 transcription. p400, a human Swr1 homolog, is required for the localization of H2A.Z, and largely colocalizes with H2A.Z at multiple promoters investigated. Notably, the presence of sequence-specific transcription factors, such as p53 and Myc, provides positioning cues that direct the location of H2A.Z-containing nucleosomes within these promoters. Collectively, this study strongly suggests that certain sequence-specific transcription factors regulate transcription, in part, by preferentially positioning histone variant H2A.Z within chromatin. This H2A.Z-centered process is part of an epigenetic process for modulating gene expression. C1 Univ Sherbrooke, Fac Sci, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Univ Sherbrooke, Fac Sci, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada. EM David_Livingston@dfci.harvard.edu; Luc.Gaudreau@USherbrooke.ca NR 49 TC 126 Z9 128 U1 2 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 2007 VL 21 IS 15 BP 1869 EP 1881 DI 10.1101/gad.1545707 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 196RW UT WOS:000248500700004 PM 17671089 ER PT J AU Betson, M Settleman, J AF Betson, Martha Settleman, Jeffrey TI A Rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development SO GENETICS LA English DT Article ID ZIPPER-LIKE SEQUENCES; SMALL GTPASE-RHO; ACTIN CYTOSKELETON; POTENTIAL EFFECTOR; CATALYTIC DOMAIN; PLASMA-MEMBRANE; GENE-EXPRESSION; LIM-KINASE; PKN-BETA; ACTIVATION AB The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu RI Betson, Martha/D-3818-2014 OI Betson, Martha/0000-0002-4220-3290 FU NCI NIH HHS [R01 CA 62142, R01 CA062142] NR 61 TC 9 Z9 12 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 2007 VL 176 IS 4 BP 2201 EP 2212 DI 10.1534/genetics.107.072967 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 211NH UT WOS:000249530000023 PM 17507675 ER PT J AU Metzler, RA Evans, JS Zhou, D Beniash, E Wilt, F Abrecht, M Coppersmith, SN Gilbert, PUPA AF Metzler, Rebecca A. Evans, John Spencer Zhou, Dong Beniash, Elia Wilt, Fred Abrecht, Mike Coppersmith, Susan N. Gilbert, P. U. P. A. TI Probing the organic-mineral interface (OMI) at the molecular level in model biominerals SO GEOCHIMICA ET COSMOCHIMICA ACTA LA English DT Meeting Abstract CT 17th Annual V M Goldschmidt Conference CY AUG, 2007 CL Cologne, GERMANY C1 Univ Wisconsin, Dept Phys, Madison, WI 53706 USA. NYU, Ctr Biomol Mass Spect, Phys Chem Lab, New York, NY 10010 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Wisconsin, Ctr Synchrotron Radiat, Stoughton, WI 53589 USA. EM pupa@physics.wisc.edu RI Gilbert, Pupa/A-6299-2010 OI Gilbert, Pupa/0000-0002-0139-2099 NR 5 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0016-7037 J9 GEOCHIM COSMOCHIM AC JI Geochim. Cosmochim. Acta PD AUG PY 2007 VL 71 IS 15 SU S BP A658 EP A658 PG 1 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 200VC UT WOS:000248789901532 ER PT J AU Lee, S Garner, EIO Welch, WR Berkowitz, RS Mok, SC AF Lee, Sunyoung Garner, Elizabeth I. O. Welch, William R. Berkowitz, Ross S. Mok, Samuel C. TI Over-expression of hypoxia-inducible factor 1 alpha in ovarian clear cell carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE HIF-1 alpha; VHL; ovarian carcinoma ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; TUMOR-SUPPRESSOR GENE; RENAL-CARCINOMA; CANCER; ALPHA; CHEMOTHERAPY; ANGIOGENESIS; HIF-1-ALPHA; RESISTANCE; MUTATIONS AB Objective. Unlike other histological types of epithelial ovarian carcinoma, ovarian clear cell carcinoma is known to have very poor response to therapy even when discovered in its early stages. Since tumor hypoxia has been shown to be strongly associated with poor prognosis, deregulation of the representative factor of tissue hypoxia; hypoxia-inducible factor 1 alpha (HIF-1 alpha) and related protein; Von Hippel-Lindau (VHL) may be associated with poor prognosis of ovarian clear cell carcinoma. Methods. Immunolocalization of both HIF-1 alpha and VHL was performed on 56 cases of paraffin-embedded tissue sections of four different histological types of epithelial ovarian carcinoma and 5 cases of benign ovarian tumors as a control. Quantitative RT-PCR analysis of both HIF1A and VHL was performed on RNA isolated from 61 microdissected frozen tissues of four different histological types of epithelial ovarian carcinoma and 6 cases of normal ovarian epithelial cells. Expression levels of HIF-1 alpha and VHL in different histological types and correlation between HIF-1 alpha and VHL were determined by nonparametric analysis by Kruskal-Wallis and Spearman's test. Results. HIF-1 alpha expression levels were significantly higher in ovarian clear cell carcinoma than in other histological types (P=0.001). We found no correlation between mRNA and protein expression level in any type of carcinoma specimens. Among endometrioid, serous, and mucinous carcinoma, there were no differences in HIF-1 alpha expression (P=0.643). There was a negative correlation between HIF-1 alpha and VHL in serous (r=-0.661, P=0.027) and in endometrioid carcinoma (r=-0.657 P=0.039), but no correlation was found between HIF-1 alpha and VHL expression levels in ovarian clear cell carcinoma (P=0.60). Conclusions. The results suggest that the role of hypoxia may change according to the histological type of ovarian carcinoma. High expression of HIF-1 alpha and its independence from VHL in ovarian clear cell carcinoma may confer chemoresistance in this histological type. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Pochon CHA Univ, Bundang CHA Hosp, Dept Obstet & Gynecol, Songnam, South Korea. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Sch Med, BLI-447,221 Longwood Ave, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu FU NCI NIH HHS [R33CA103595, P50 CA105009, P50 CA105009-030002, R01 CA133057, R33 CA103595, R33 CA103595-04]; PHS HHS [P50105009] NR 30 TC 34 Z9 41 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2007 VL 106 IS 2 BP 311 EP 317 DI 10.1016/j.ygyno.2007.03.041 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 197VX UT WOS:000248585700006 PM 17532031 ER PT J AU Volpp, KG Stone, R Lave, JR Jha, AK Pauly, M Klusaritz, H Chen, HY Cen, LY Brucker, N Polsky, D AF Volpp, Kevin G. Stone, Roslyn Lave, Judith R. Jha, Ashish K. Pauly, Mark Klusaritz, Heather Chen, Huanyu Cen, Liyi Brucker, Nancy Polsky, Daniel TI Is thirty-day hospital mortality really lower for black veterans compared with white veterans? SO HEALTH SERVICES RESEARCH LA English DT Article DE hospital mortality; racial disparities; hospitals; veterans ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE-SYSTEM; QUALITY-OF-LIFE; RACIAL-DIFFERENCES; ADMINISTRATIVE DATA; MEDICARE BENEFICIARIES; HEART-FAILURE; OUTCOMES; DISPARITIES; AFFAIRS AB Objective. To examine the source of observed lower risk-adjusted mortality for blacks than whites within the Veterans Affairs (VA) system by accounting for hospital site where treated, potential under-reporting of black deaths, discretion on hospital admission, quality improvement efforts, and interactions by age group. Data Sources. Data are from the VA Patient Treatment File on 406,550 hospitalizations of veterans admitted with a principal diagnosis of acute myocardial infarction, stroke, hip fracture, gastrointestinal bleeding, congestive heart failure, or pneumonia between 1996 and 2002. Information on deaths was obtained from the VA Beneficiary Identification Record Locator System and the National Death Index. Study Design. This was a retrospective observational study of hospitalizations throughout the VA system nationally. The primary outcome studied was all-location mortality within 30 days of hospital admission. The key study variable was whether a patient was black or white. Principal Findings. For each of the six study conditions, unadjusted 30-day mortality rates were significantly lower for blacks than for whites (p <.01). These results did not vary after adjusting for hospital site where treated, more complete ascertainment of deaths, and in comparing results for conditions for which hospital admission is discretionary versus nondiscretionary. There were also no significant changes in the degree of difference by race in mortality by race following quality improvement efforts within VA. Risk-adjusted mortality was consistently lower for blacks than for whites only within the population of veterans over age 65. Conclusions. Black veterans have significantly lower 30-day mortality than white veterans for six common, high severity conditions, but this is generally limited to veterans over age 65. This differential by age suggests that it is unlikely that lower 30-day mortality rates among blacks within VA are driven by treatment differences by race. C1 Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Hlth Care Syst Dept, Philadelphia, PA 19104 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Penn, Sch Social Sci Policy & Practice, Philadelphia, PA 19104 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), Philadelphia Vet Affairs Med Ctr, CHERP, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 56 TC 29 Z9 29 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2007 VL 42 IS 4 BP 1613 EP 1631 DI 10.1111/j.1475-6773.2006.00688.x PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 184SM UT WOS:000247662300010 PM 17610440 ER PT J AU Carpiac-Claver, M Guzman, JS Castle, SC AF Carpiac-Claver, Maria Guzman, Jenice S. Castle, Steven C. TI The comprehensive care clinic SO HEALTH & SOCIAL WORK LA English DT Article ID HEALTH-CARE; COMORBIDITY C1 Univ Calif Los Angeles, Dept SocialWelfare, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Nursing, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Carpiac-Claver, M (reprint author), Univ Calif Los Angeles, Dept SocialWelfare, 3225 Publ Policy Bldg, Los Angeles, CA 90095 USA. EM mcarpiac@ucla.edu NR 18 TC 1 Z9 1 U1 0 U2 0 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0360-7283 J9 HEALTH SOC WORK JI Health Soc. Work PD AUG PY 2007 VL 32 IS 3 BP 219 EP 223 PG 5 WC Social Work SC Social Work GA 202XT UT WOS:000248938600008 PM 17896679 ER PT J AU Nakazawa, G Finn, AV Virmani, R AF Nakazawa, Gaku Finn, Aloke V. Virmani, Renu TI Virtual histology: does it add anything? SO HEART LA English DT Editorial Material ID INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; CORONARY PLAQUE; IMPACT C1 CVPath Inst Inc, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Cardiac Unit, Dept Internal Med, Boston, MA 02114 USA. RP Nakazawa, G (reprint author), CVPath Inst Inc, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 14 TC 4 Z9 4 U1 0 U2 0 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 AUG PY 2007 VL 93 IS 8 BP 897 EP 898 DI 10.1136/hrt.2006.109371 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 190JF UT WOS:000248054400003 PM 17639103 ER PT J AU d'Avila, A Thiagalingam, A AF d'Avila, Andre Thiagalingam, Aravinda TI Spot cryoablation: A cool new way to achieve pulmonary vein isolation SO HEART RHYTHM LA English DT Editorial Material ID ATRIAL-FIBRILLATION; ABLATION; TACHYARRHYTHMIAS; EFFICACY; SAFETY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP d'Avila, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Biglow 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2007 VL 4 IS 8 BP 997 EP 998 DI 10.1016/j.hrthm.2007.04.020 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 199ST UT WOS:000248716200003 PM 17675070 ER PT J AU Heist, EK Singh, JP Mela, T Ruskin, JN AF Heist, E. Kevin Singh, Jagmeet P. Mela, Theofanie Ruskin, Jeremy N. TI Coronary venospasm causing chest pain during implantation of cardiac resynchronization therapy SO HEART RHYTHM LA English DT Article ID ANGINA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA. Charlton Mem Hosp, Cardiac Electrophys Lab, Fall River, MA USA. RP Heist, EK (reprint author), Massachusetts Gen Hosp, Arrhythmia Serv, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM kheist@partners.org NR 4 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2007 VL 4 IS 8 BP 1108 EP 1109 DI 10.1016/j.hrthm.2006.12.039 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 199ST UT WOS:000248716200025 PM 17675092 ER PT J AU Graham, DY Lu, H Yamaoka, Y AF Graham, David Y. Lu, Hong Yamaoka, Yoshio TI A report card to grade Helicobacter pylori therapy SO HELICOBACTER LA English DT Editorial Material ID PROTON PUMP INHIBITOR; 7-DAY TRIPLE-THERAPY; RANDOMIZED-TRIAL; SEQUENTIAL TREATMENT; QUADRUPLE THERAPY; NONULCER DYSPEPSIA; ERADICATION RATES; UNITED-STATES; PEPTIC-ULCER; DOUBLE-BLIND AB Helicobacter pylori causes a serious bacterial infectious disease, and the expectations of therapy should reflect this fact. increasing antibiotic resistance, especially to clarithromycin, has significantly undermined the effectiveness of legacy triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin. Current cure rates are consistently below 80% intention-to-treat, the accepted threshold separating acceptable from unacceptable treatment results. Grading clinical studies into effectiveness categories using prespecified criteria would allow clinicians to objectively identify and compare regimens. We offer a therapy report card similar to that used to grade the performance of school children. The intention-to-treat cure rate categories are: For unacceptable (<= 80%), D or poor (81-84%), C or fair (85-89%), B or good (90-95%), and A or excellent (95-100%). The category of "excellent" is based on the cure rates expected with other prevalent bacterial infectious diseases. We propose that only therapies that score "excellent" (grade = A) should be prescribed. Regimens scoring as B or good" can be used if "excellent" results are not obtainable. In most regions legacy triple therapy should be abandoned as unacceptable. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Dis, Renji Hosp,Dept Gastroenterol, Shanghai 200030, Peoples R China. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK 56338] NR 36 TC 145 Z9 164 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2007 VL 12 IS 4 BP 275 EP 278 DI 10.1111/j.1523-5378.2007.00518.x PG 4 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 204BM UT WOS:000249017800001 PM 17669098 ER PT J AU Yamaoka, Y Yamauchi, K Choi, I Oigiwara, H Graham, DY AF Yamaoka, Y. Yamauchi, K. Choi, I. Oigiwara, H. Graham, D. Y. TI Up-regulation of interleukin-18 in Helicobacter pylori infection SO HELICOBACTER LA English DT Meeting Abstract CT 20th International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation CY SEP 20-22, 2007 CL Istanbul, TURKEY SP European Helicobacter Study Grp C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 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 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2007 VL 12 IS 4 BP 400 EP 400 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 204BM UT WOS:000249017800073 ER PT J AU Timm, J Li, B Daniels, MG Bhattacharya, T Reyor, LL Allgaier, R Kuntzen, T Fischer, W Nolan, BE Duncan, J zur Wiesch, JS Kim, AY Frahm, N Brander, C Chung, RT Lauer, GM Korber, BT Allen, TM AF Timm, Joerg Li, Bin Daniels, Marcus G. Bhattacharya, Tanmoy Reyor, Laura L. Allgaier, Rachel Kuntzen, Thomas Fischer, Will Nolan, Brian E. Duncan, Jared Schulze zur Wiesch, Julian Kim, Arthur Y. Frahm, Nicole Brander, Christian Chung, Raymond T. Lauer, Georg M. Korber, Bette T. Allen, Todd M. TI Human leukocyte antigen-associated sequence polymorphisms in hepatitis C virus reveal reproducible immune responses and constraints on viral evolution SO HEPATOLOGY LA English DT Article ID CD8(+) T-CELLS; IN-VITRO PROLIFERATION; ESCAPE MUTATIONS; HCV INFECTION; LYMPHOCYTE RESPONSE; DOMINANT INFLUENCE; HIV POLYMORPHISMS; HLA; TYPE-1; PERSISTENCE AB CD8(+) T cell responses play a key role in governing the outcome of hepatitis C virus (HCV) infection, and viral evolution enabling escape from these responses may contribute to the inability to resolve infection. To more comprehensively examine the extent of CD8 escape and adaptation of HCV to human leukocyte antigen (HLA) class I restricted immune pressures on a population level, we sequenced all non-structural proteins in a cohort of 70 chronic HCV genotype la-infected subjects (28 subjects with HCV monoinfection and 42 with HCV/human immunodeficiency virus [HIV] coinfection). Linking of sequence polymorphisms with HLA allele expression revealed numerous HLA-associated polymorphisms across the HCV proteome. Multiple associations resided within relatively conserved regions, highlighting attractive targets for vaccination. Additional mutations provided evidence of HLA-driven fixation of sequence polymorphisms, suggesting potential loss of some CD8 targets from the population. In a subgroup analysis of mono- and co-infected subjects some associations lost significance partly due to reduced power of the utilized statistics. A phylogenetic analysis of the data revealed the substantial influence of founder effects upon viral evolution and HLA associations, cautioning against simple statistical approaches to examine the influence of host genetics upon sequence evolution of highly variable pathogens. Conclusion: These data provide insight into the frequency and reproducibility of viral escape from CD8(+) T cell responses in human HCV infection, and clarify the combined influence of multiple forces shaping the sequence diversity of HCV and other highly variable pathogens. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Infect Dis Div, Boston, MA 02115 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Allen, TM (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Fischer, Will/B-1323-2013; Bhattacharya, Tanmoy/J-8956-2013; Allen, Todd/F-5473-2011; OI Fischer, Will/0000-0003-4579-4062; Bhattacharya, Tanmoy/0000-0002-1060-652X; Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI067926, AI066345, P01 AI061734, P01 AI061734-02, R01 AI067926, U19 AI066345] NR 42 TC 73 Z9 76 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2007 VL 46 IS 2 BP 339 EP 349 DI 10.1002/hep.21702 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 196SF UT WOS:000248501600010 PM 17559151 ER PT J AU Moss, RB Milla, C Colombo, J Accurso, F Zeitlin, PL Clancy, JP Spencer, LT Pilewski, J Waltz, DA Dorkin, HL Ferkol, T Pian, M Ramsey, B Carter, BJ Martin, DB Heald, AE AF Moss, Richard B. Milla, Carlos Colombo, John Accurso, Frank Zeitlin, Pamela L. Clancy, John P. Spencer, L. Terry Pilewski, Joseph Waltz, David A. Dorkin, Henry L. Ferkol, Thomas Pian, Mark Ramsey, Bonnie Carter, Barrie J. Martin, Dana B. Heald, Alison E. TI Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: A Randomized placebo-controlled phase 2B trial SO HUMAN GENE THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; TRANSMEMBRANE CONDUCTANCE REGULATOR; GENE-THERAPY; MAXILLARY SINUS; DOUBLE-BLIND; LUNG-DISEASE; AIRWAY; EXPRESSION; TGAAVCF; SAFETY AB Previous studies have demonstrated that delivery of a recombinant adeno-associated virus ( AAV) vector encoding the complete human cystic fibrosis transmembrane regulator ( CFTR) cDNA ( tgAAVCF) to the nose, sinus, and lungs of subjects with cystic fibrosis ( CF) was safe and well tolerated. In a small randomized, double-blind study of three doses of aerosolized tgAAVCF or placebo at 30-day intervals, encouraging but nonsignificant trends in pulmonary function and induced sputum interleukin 8 ( IL-8) levels were seen at early time points. This larger study was conducted to verify these trends. One hundred and two subjects aged 12 years and older with mild-to-moderate cystic fibrosis ( forced expiratory flow in 1 sec [ FEV1] : 60% predicted) were randomized to two aerosolized doses of 1 x 10(13) DNase-resistant particles of tgAAVCF ( n = 51) or matching placebo ( n = 51) administered 30 days apart. Although tgAAVCF was well tolerated, the study did not meet its primary efficacy end point of statistically significant improvement in FEV1 30 days after initial administration of tgAAVCF compared with placebo. There were no significant differences in spirometric lung function over time, induced sputum biologic markers, or days of antibiotic use in either treatment group. Thus repeated doses of aerosolized tgAAVCF were safe and well tolerated, but did not result in significant improvement in lung function over time. Because gene transfer is the simplest, most basic way to correct the underlying genetic defect that leads to disease in CF, further research is warranted to develop an effective gene transfer agent for the treatment of CF. C1 Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Nebraska, Dept Pediat, Lincoln, NE 68588 USA. Univ Colorado, Dept Pediat, Denver, CO 80218 USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21287 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35233 USA. Univ Florida, Dept Pediat, Gainesville, FL 32611 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. Childrens Hosp, Dept Resp Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pediat Pulm, Boston, MA 02114 USA. Washington Univ, Dept Pediat, St Louis, MO 63110 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92123 USA. Childrens Hosp, Div Pulm, Seattle, WA 98105 USA. CF Therapeut Dev Network Coordinating Ctr, Seattle, WA 98105 USA. Targeted Genet, Seattle, WA 98101 USA. RP Moss, RB (reprint author), Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. EM rmoss@stanford.edu OI Milla, Carlos/0000-0001-5515-3053 FU NCRR NIH HHS [RR00036, M01-RR00070, RR00032, RR00052, RR00069, RR00082, RR00084, RR00400, RR00827, RR01066, RR02172] NR 27 TC 120 Z9 122 U1 0 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 2007 VL 18 IS 8 BP 726 EP 732 DI 10.1089/hum.2007.022 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 205OU UT WOS:000249124900005 PM 17685853 ER PT J AU Kuhn, A Goldstein, DR Hodges, A Strand, AD Sengstag, T Kooperberg, C Becanovic, K Pouladi, MA Sathasivam, K Cha, JHJ Hannan, AJ Hayden, MR Leavitt, BR Dunnett, SB Ferrante, RJ Albin, R Shelbourne, P Delorenzi, M Augood, SJ Faull, RLM Olson, JM Bates, GP Jones, L Luthi-Carter, R AF Kuhn, Alexandre Goldstein, Darlene R. Hodges, Angela Strand, Andrew D. Sengstag, Thierry Kooperberg, Charles Becanovic, Kristina Pouladi, Mahmoud A. Sathasivam, Kirupa Cha, Jang-Ho J. Hannan, Anthony J. Hayden, Michael R. Leavitt, Blair R. Dunnett, Stephen B. Ferrante, Robert J. Albin, Roger Shelbourne, Peggy Delorenzi, Mauro Augood, Sarah J. Faull, Richard L. M. Olson, James M. Bates, Gillian P. Jones, Lesley Luthi-Carter, Ruth TI Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage SO HUMAN MOLECULAR GENETICS LA English DT Article ID KNOCK-IN MICE; MOUSE MODEL; TRANSGENIC MICE; TRANSCRIPTIONAL DYSREGULATION; REPRESSES TRANSCRIPTION; MOTOR DYSFUNCTION; BINDING-PROTEIN; SET ENRICHMENT; PROBE LEVEL; INTERACTS AB To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2(Q150/Q150), 18-month Hdh(Q92/Q92) and 2-year-old YAC128 animals also exhibited significant HID-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials. C1 Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. Swiss Inst Expt Canc Res, Natl Ctr Competence Res NCCR Mol Oncol, CH-1066 Epalinges, Switzerland. SIB, CH-1066 Epalinges, Switzerland. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF14 4XN, Wales. Univ Wales Coll Med, Dept Med Genet & Med, Cardiff CF14 4XN, Wales. Univ Cardiff Wales, Sch Biosci, Cardiff CF14 4XN, Wales. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada. Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. Massachusetts Gen Hosp East, MassGen Inst Neurodegenerat Dis MIND, Charlestown, MA 02129 USA. Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. Univ Melbourne, Natl Neurosci Facil, Howard Florey Inst, Melbourne, Vic 3010, Australia. Boston Univ, Sch Med, Dept Neurol, Bedford, MA USA. Boston Univ, Sch Med, Dept Pathol, Bedford, MA USA. Boston Univ, Sch Med, Dept Psychiat, Bedford, MA USA. Bedford Vet Affairs Med Ctr, Bedford, MA USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Ann Arbor Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. Univ Glasgow, Fac Biomed & Life Sci, Div Mol Genet, Glasgow G11 6NU, Lanark, Scotland. Univ Auckland, Dept Anat & Radiol, Auckland 1, New Zealand. RP Luthi-Carter, R (reprint author), Ecole Polytech Fed Lausanne, AI 2138,Stn 15, CH-1015 Lausanne, Switzerland. EM ruth.luthi-carter@epfl.ch RI Dunnett, Stephen/A-5869-2010; Hodges, Angela/C-5676-2011; turton, miranda/F-4682-2011; Hayden, Michael/D-8581-2011; Leavitt, Blair/G-1934-2012; Bates, Gillian/E-1146-2012; Pouladi, Mahmoud/B-8743-2016 OI Dunnett, Stephen/0000-0003-1826-1578; Hayden, Michael/0000-0001-5159-1419; Bates, Gillian/0000-0002-4041-6305; Pouladi, Mahmoud/0000-0002-9030-0976 FU Medical Research Council [G0500794, G9810900] NR 57 TC 185 Z9 187 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2007 VL 16 IS 15 BP 1845 EP 1861 DI 10.1093/hmg/ddm133 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 211BZ UT WOS:000249500600008 PM 17519223 ER PT J AU Longacre, TA Oliva, E Soslow, RA AF Longacre, Teri A. Oliva, Esther Soslow, Robert A. CA Assoc Directors Anatomic Surgical TI Recommendations for the reporting of fallopian tube neoplasms SO HUMAN PATHOLOGY LA English DT Article DE fallopian tube; carcinoma; ADASP ID OVARIAN-CANCER; RISK; OOPHORECTOMY; CARCINOMA; LIGATION; CARRIERS AB Primary malignancies of the fallopian tube are extremely uncommon, in part due to (admittedly arbitrary) definitional criteria. By convention, epithelial tumors that involve the ovary or peritoneal surfaces are considered to have arisen either in the ovary or endometrium or, in absence of significant ovarian or endometrial involvement, in the peritoneum, irrespective of whether or not the fallopian tube mucosa is also involved. Evidence from the World Health Organization and more recently, from case-control studies of BRCA mutation carriers suggests the fallopian tube may have a more direct role in the development of at least some of these carcinomas. An alternative hypothesis for the origin of ovarian and peritoneal carcinoma has even been proposed, based on the concept of transport and implantation of malignant cells from the tube to the ovary and peritoneum. Malignancies in the fallopian tube can therefore be classified as (1) arising primarily in the fallopian tube, either from preexisting endometriosis (or more rarely, a mature teratoma) or directly from tubal mucosa with metastasis to adjacent tissues; (2) arising in the ovary, endometrium, or peritoneum with metastasis to the tubal serosa or mucosa; or (3) arising primarily in the fallopian tube as well as in the ovary, endometrium, or peritoneum (simultaneous primary tumors). Since there are currently no evidence based criteria for distinguishing primary tubal carcinoma from primary ovarian or primary endometrial carcinoma in patients with high stage disease, the Association of Directors of Anatomic and Surgical Pathology recommended strategies for assignment of site of origin are based on current standard practices. (c) 2007 Elsevier Inc. All rights reserved. C1 Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Longacre, TA (reprint author), Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. EM longacre@stanford.edu OI Soslow, Robert/0000-0002-7269-5898 NR 10 TC 15 Z9 15 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2007 VL 38 IS 8 BP 1160 EP 1163 DI 10.1016/j.humpath.2006.11.010 PG 4 WC Pathology SC Pathology GA 194IY UT WOS:000248339300006 PM 17270244 ER PT J AU Drake, TA Braun, J Marchevsky, A Kohane, IS Fletcher, C Chueh, H Beckwith, B Berkowicz, D Kuo, F Zeng, QT Balis, U Holzbach, A McMurry, A Gee, CE McDonald, CJ Schadow, G Davis, M Hattab, EM Blevins, L Hook, J Becich, M Crowley, RS Taube, SE Berman, J AF Drake, Thomas A. Braun, Jonathan Marchevsky, Alberto Kohane, Isaac S. Fletcher, Christopher Chueh, Henry Beckwith, Bruce Berkowicz, David Kuo, Frank Zeng, Qing T. Balis, Ulysses Holzbach, Ana McMurry, Andrew Gee, Connie E. McDonald, Clement J. Schadow, Gunther Davis, Mary Hattab, Eyas M. Blevins, Lonnie Hook, John Becich, Michael Crowley, Rebecca S. Taube, Sheila E. Berman, Jules CA Member Shared Pathology Informatic TI A system for sharing routine surgical pathology specimens across institutions: the Shared Pathology Informatics Network SO HUMAN PATHOLOGY LA English DT Article DE pathology; informatics; internet; tissue bank; database ID DATA INTEGRATION; SOFTWARE; LANGUAGE AB This report presents an overview for pathologists of the development and potential applications of a novel Web enabled system allowing indexing and retrieval of pathology specimens across multiple institutions. The system was developed through the National Cancer Institute's Shared Pathology Informatics Network program with the goal of creating a prototype system to find existing pathology specimens derived from routine surgical and autopsy procedures ("paraffin blocks") that may be relevant to cancer research. To reach this goal, a number of challenges needed to be met. A central aspect was the development of an informatics system that supported Web-based searching while retaining local control of data. Additional aspects included the development of an eXtensible Markup Language schema, representation of tissue specimen annotation, methods for deidentifying pathology reports, tools for autocoding critical data from these reports using the Unified Medical Language System, and hierarchies of confidentiality and consent that met or exceeded federal requirements. The prototype system supported Web-based querying of millions of pathology reports from 6 participating institutions across the country in a matter of seconds to minutes and the ability of bona fide researchers to identify and potentially to request specific paraffin blocks from the participating institutions. With the addition of associated clinical and outcome information, this system could vastly expand the pool of annotated tissues available for cancer research as well as other diseases. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Avid Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Biomed Informat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Syst Grp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15261 USA. NCI, Bethesda, MD 20892 USA. RP Drake, TA (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Avid Geffen Sch Med, Box 951732,AL-124, Los Angeles, CA 90095 USA. EM tdrake@mednet.ucla.edu RI Kohane, Isaac Kohane/K-3716-2012; Hattab, Eyas/E-9342-2016 OI Kohane, Isaac Kohane/0000-0003-2192-5160; Hattab, Eyas/0000-0002-3660-6261 FU NCI NIH HHS [1UO1 CA91429, P30 CA016042, U01 CA91343] NR 28 TC 16 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2007 VL 38 IS 8 BP 1212 EP 1225 DI 10.1016/j.humpath.2007.01.007 PG 14 WC Pathology SC Pathology GA 194IY UT WOS:000248339300014 PM 17490722 ER PT J AU Abedini, A Shoelson, SE AF Abedini, Andisheh Shoelson, Steven E. TI Inflammation and obesity - Stamping out insulin resistance? SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID HOMEOSTASIS C1 Joslin Diabet Ctr, Boston, MA 02115 USA. RP Shoelson, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM steven.shoelson@joslin.harvard.edu OI Abedini, Andisheh/0000-0002-1396-1420 NR 5 TC 11 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD AUG-SEP PY 2007 VL 85 IS 6 BP 399 EP 400 DI 10.1038/sj.icb.7100107 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 212MV UT WOS:000249601500002 PM 17646847 ER PT J AU Taubman, MA Han, XZ LaRosa, KB Socransky, SS Smith, DJ AF Taubman, Martin A. Han, Xiaozhe LaRosa, Karen B. Socransky, Sigmund S. Smith, Daniel J. TI Periodontal bacterial DNA suppresses the immune response to mutans streptococcal glucosyltransferase SO INFECTION AND IMMUNITY LA English DT Article ID CYTOKINE SIGNALING SOCS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INDUCED MACROPHAGE ACTIVATION; PORPHYROMONAS-GINGIVALIS; CPG MOTIFS; DENTAL-CARIES; GENOMIC DNA; MUCOSAL IMMUNIZATION; EPITHELIAL-CELLS; VACCINE AB Certain CpG motifs found in bacterial DNA enhance immune responses through Toll-like receptor 9 (TLR-9) and may also demonstrate adjuvant properties. Our objective was to determine if DNA from bacteria associated with periodontal disease could affect the immune response to other bacterial antigens in the oral cavity. Streptococcus sobrinus glucosyltransferase (GTF), an enzyme involved in dental caries pathogenesis, was used as a test antigen. Rowett rats were injected with aluminum hydroxide (alum) with buffer, alum-GTF, or alum-GTF together with either Escherichia coli DNA, Fusobacterium nucleatum DNA, or Porphyromonas gingivalis DNA. Contrary to expectation, animals receiving alum-GTF plus bacterial DNA (P. gingivalis in particular) demonstrated significantly reduced serum immunoglobulin G (IgG) antibody, salivary IgA antibody, and T-cell proliferation to GTF compared to animals immunized with alum-GTF alone. A diminished antibody response was also observed after administration of alum-GTF with the P. gingivalis DNA either together or separately, indicating that physical complexing of antigen and DNA was not responsible for the reduction in antibody. Since TLR triggering by DNA induces synthesis of prospective suppressive factors (e.g., suppressor of cytokine signaling [SOCS]), the effects of P. gingivalis DNA and GTF exposure on rat splenocyte production of SOCS family molecules and inflammatory cytokines were investigated in vitro. P. gingivalis DNA significantly up-regulated SOCS1 and SOCS5 expression and down-regulated interleukin-10 expression by cultured splenocytes. These results suggested that DNA from periodontal disease-associated bacteria did not enhance, but in fact suppressed, the immune response to a protein antigen from cariogenic streptococci, potentially through suppressive SOCS components triggered by innate mechanisms. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM mtaubman@forsyth.org FU NIDCR NIH HHS [R56 DE004733, R01 DE003420, DE 04733, R01 DE004733, DE 03420, R37 DE003420] NR 55 TC 6 Z9 6 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 4088 EP 4096 DI 10.1128/IAI.00623-07 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200045 PM 17517867 ER PT J AU Chang, HT Krezolek, D Johnson, S Parada, JP Evans, CT Gerding, DN AF Chang, Heidi T. Krezolek, Dorota Johnson, Stuart Parada, Jorge P. Evans, Charlesnika T. Gerding, Dale N. TI Onset of symptoms and time to diagnosis of Clostridium difficile - Associated disease following discharge from an acute care hospital SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; DIARRHEA AB Objective. To identify patients with a diagnosis of Clostridium difficile-associated disease (CDAD) in the ambulatory care setting and determine the relationship of symptom onset and diagnosis to prior hospitalization and exposure to antimicrobials. Design. Single-center, retrospective study. Methods. Medical records were reviewed for outpatients and hospitalized patients with a stool assay positive for C. difficile toxin A from January 1998 through March 2005. Patients with recurrent CDAD or residing in an extended-care facility were excluded. CDAD in patients who had been hospitalized in the 100 days prior to diagnosis was considered potentially hospital-associated. Results. Of the 84 patients who met the inclusion criteria, 75 (89%) received a diagnosis 1-60 days after hospital discharge (median, 12 days), and 71 (85%) received a diagnosis within 30 days after discharge. Of the 69 patients whose records contained information regarding time of symptom onset, 62 (90%) developed diarrhea within 30 days of a previous hospital discharge, including 7 patients with symptom onset prior to discharge and 9 with onset on the day of discharge. The median time from symptom onset to diagnosis was 6 days. Of 84 patients, 77 (92%) had received antimicrobials during a prior hospitalization, but 55 (65%) received antimicrobials both as inpatients and as outpatients. Conclusion. If all cases of CDAD diagnosed within 100 days of hospital discharge were assumed to be hospital-associated, 71 (85%) of 84 patients with CDAD were identified within 30 days, and 75 (89%) of 84 were identified by day 60. Continued outpatient antimicrobial exposure confounds determination of whether late-onset cases are community-or hospital-associated. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res & Res Serv, Res Serv 151, Hines, IL 60141 USA. Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res & Res Serv, Res Serv 151, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM dale.gerding2@va.gov NR 13 TC 31 Z9 31 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2007 VL 28 IS 8 BP 926 EP 931 DI 10.1086/519178 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 205NS UT WOS:000249121500006 PM 17620239 ER PT J AU Chan, MM Lu, X Merchant, FM Iglehart, JD Miron, PL AF Chan, Maren M. Lu, Xin Merchant, Faisal M. Iglehart, James Dirk Miron, Penelope L. TI Serial transplantation of NMU-induced rat mammary tumors: A model of human breast cancer progression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; microarray; animal model; mammary tumor; invasion ID GENE-EXPRESSION PROFILES; METHYL-N-NITROSOUREA; CDNA MICROARRAY; INVASIVE-CARCINOMA; MOLECULAR MARKERS; TISSUE INHIBITOR; DUCTAL CARCINOMA; TRANSGENIC MICE; METASTASIS; CELLS AB Human breast cancer is a heterogeneous disease that appears to progress from an in situ tumor to invasive cancer. Little is known about the molecular events driving this progression. Although microarray technology has helped us understand the genetic heterogeneity of breast cancer, its application to studying the transition from in situ to invasive disease is limited by the inability to follow the progression of a single patient's tumor. We previously used rat specific microarrays to show that N-methyl-N-nitrosourea induced tumors are similar to low-grade estrogen- receptor positive human breast cancer. Here, we transplanted these tumors through 5 generations of syngeneic hosts, and studied 65 resulting tumors. Most transplanted tumors gradually progressed from a noninvasive, low-grade cancer to a higher-grade invasive disease, losing p63 localization and basement membrane integrity. Invasive cancers frequently demonstrated a more mesenchymal phenotype with increased vimentin expression. Additionally, a unique transplant series is described with a phenotype similar to human basal-like breast cancer. Rat-specific Affymetrix gene arrays containing 15,866 gene probes identified genes that differentiated highly invasive tumors from those of low invasive potential. A linear regression analysis was used to find genes whose change in expression paralleled increasing invasive features independent of the transplant lineage of origin. Genes identified were assigned membership in cell adhesion, signal transduction, cell cycle and extracellular matrix groups, among others. This animal model overcomes the difficulty in studying human breast cancer progression. Our data support a gradual and continuous alteration in programs of gene expression during breast cancer invasion. (c) 2007 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Miron, PL (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Room 1068,Smith Bldg, Boston, MA 02115 USA. EM penelope_miron@dfci.harvard.edu FU NCI NIH HHS [T32 CA09535-18]; NHGRI NIH HHS [1R01HG02341] NR 68 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 1 PY 2007 VL 121 IS 3 BP 474 EP 485 DI 10.1002/ijc.22684 PG 12 WC Oncology SC Oncology GA 180ZV UT WOS:000247407400002 PM 17405122 ER PT J AU Stillman, AE Oudkerk, M Ackerman, M Becker, CR Buszman, PE de Feyter, PJ Hoffmann, U Keadey, MT Marano, R Lipton, MJ Raff, GL Reddy, GP Rees, MR Rubin, GD Schoepf, UJ Tarulli, G van Beek, EJR Wexler, L White, CS AF Stillman, Arthur E. Oudkerk, Matthijs Ackerman, Margaret Becker, Christoph R. Buszman, Pawel E. de Feyter, Pim J. Hoffmann, Udo Keadey, Matthew T. Marano, Riccardo Lipton, Martin J. Raff, Gilbert L. Reddy, Gautham P. Rees, Michael R. Rubin, Geoffrey D. Schoepf, U. Joseph Tarulli, Giuseppe van Beek, Edwin J. R. Wexler, Lewis White, Charles S. TI Use of multidetector computed tomography for the assessment of acute chest pain: a consensus statement of the North American Society of Cardiac Imaging and the European Society of Cardiac Radiology SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE guidelines; acute chest pain ID TIMI RISK SCORE; NORMAL TROPONIN CONCENTRATIONS; ACUTE MYOCARDIAL-INFARCTION; ELECTRON-BEAM TOMOGRAPHY; ACUTE CORONARY SYNDROMES; CARE-UNIT ADMISSION; EMERGENCY-DEPARTMENT; TASK-FORCE; PREDICTIVE INSTRUMENT; DIAGNOSTIC-ACCURACY C1 Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands. Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON, Canada. Univ Munich, Dept Clin Radiol, Munich, Germany. Upper Silesian Heart Ctr, Dept Cardiol, Silesia, Poland. Univ Hosp Rotterdam Dijkzigt, Thoraxctr, Div Cardiol, Rotterdam, Netherlands. Erasmus Univ, Rotterdam, Netherlands. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Emory Univ, Dept Emergency Med, Atlanta, GA 30322 USA. Univ G DAnnunzio, Dept Clin Sci & Bioimaging, Sect Radiol, Chieti, Italy. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. William Beaumont Hosp, Dept Cardiol, Royal Oak, MI 48072 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Bristol Royal Infirm & Gen Hosp, Dept Clin Radiol, Bristol, Avon, England. Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Humber River Reg Hosp, Dept Radiol, Toronto, ON, Canada. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Univ Maryland, Med Ctr, Dept Diagnost Radiol, Baltimore, MD 21201 USA. RP Oudkerk, M (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands. EM M.Oudkerk@rad.umcg.nl RI Rubin, Geoff/D-2557-2010; OI Marano, Riccardo/0000-0003-2710-2093 NR 52 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD AUG PY 2007 VL 23 IS 4 BP 415 EP 427 DI 10.1007/s10554-007-9226-8 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 190JA UT WOS:000248053900001 PM 17492364 ER PT J AU Wise, TN Wiltse, CG Iosifescu, DV Sheridan, M Xu, JY Raskin, J AF Wise, T. N. Wiltse, C. G. Iosifescu, D. V. Sheridan, M. Xu, J. Y. Raskin, J. TI The safety and tolerability of duloxetine in depressed elderly patients with and without medical comorbidity SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Article ID LATE-LIFE DEPRESSION; PAINFUL PHYSICAL SYMPTOMS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MAJOR DEPRESSION; MYOCARDIAL-INFARCTION; OLDER PATIENTS; DISORDER; ILLNESS; IMPACT AB Aim and methods: The impact of medical comorbidity on the efficacy and tolerability of duloxetine in elderly patients with major depressive disorder (MDD) was investigated in this study. Data were obtained from a multicentre, randomised, double-blind, placebo-controlled study in 311 patients with MDD aged 65-89. The primary outcome measure was a prespecified composite cognitive score based on four cognitive tests: (i) Verbal Learning and Recall Test; (ii) Symbol Digit Substitution Test; (iii) 2-Digit Cancellation Test and (iv) Letter-Number Sequencing Test. Secondary measures included the Geriatric Depression Scale (GDS), 17-Item Hamilton Depression Scale (HAMD(17)), Clinical Global Impression-Severity (CGI-S) Scale, Visual Analogue Scale (VAS) for pain and 36-Item Short Form Health Survey (SF-36). Tolerability measures included adverse events reported as the reason for discontinuation and treatment-emergent adverse events (TEAEs). The consistency of the effect of duloxetine vs. placebo comparing patients with and without medical comorbidity (vascular disease, diabetes, arthritis or any of these) was investigated. Results: Overall, duloxetine 60 mg/day demonstrated significantly greater improvement compared with placebo for the composite cognitive score, GDS and HAMD(17) total scores, CGI-Severity, HAMD(17) response and remission rates, and some of the SF-36 and VAS measures. There were few significant treatment-by-comorbidity subgroup interactions for these efficacy variables, or for adverse events reported as the reason for discontinuation and common TEAEs. Conclusions: The present analyses suggested that the efficacy of duloxetine on cognition and depression in elderly patients, and its tolerability, were not largely affected by the comorbidity status. These results further support the use of duloxetine in elderly patients with MDD. C1 Eli Lilly Canada, Lilly Res Labs, Toronto, ON, Canada. Inova Fairfax Hosp, Falls Church, VA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Raskin, J (reprint author), Eli Lilly Canada, Lilly Res Labs, 3650 Danforth Ave, Toronto, ON, Canada. EM joel.raskin@lilly.com NR 51 TC 31 Z9 31 U1 5 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD AUG PY 2007 VL 61 IS 8 BP 1283 EP 1293 DI 10.1111/j.1742-1241.2007.01476.x PG 11 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 188GC UT WOS:000247906500011 PM 17590215 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time trends of mortality from Crohn's disease and ulcerative colitis SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE death rates; environmental risk factor; epidemiology; aetiology of Crohn's disease; aetiology of ulcerative colitis; inflammatory bowel disease; mortality ID INFLAMMATORY-BOWEL-DISEASE; GEOGRAPHIC-VARIATION; COUNTY; COHORT; SWEDEN AB Aims The present study served to test whether Crohn's disease and ulcerative colitis showed similarities in the temporal variation of their mortality rates among different countries. Methods Mortality data from 21 different countries between 1951 and 2005 were analysed, including Argentina, Australia, Austria, Belgium, Canada, Chile, Den-mark, England, Finland, France, Germany, Italy, Japan, Mexico, Netherlands, Scotland, Spain, Sweden, Switzerland, Taiwan and USA. The age-specific death rates of each individual country, as well as the average age-specific rates of all countries, were plotted against the period of death. Results Death rates from ulcerative colitis were initially 6-fold higher than those of Crohn's disease. Mortality from ulcerative colitis decreased continuously during the past 50 years. Mortality from Crohn's disease increased from 1951 to 1975 until reaching a similar level as mortality from ulcerative colitis. Since then the death rates of both diseases have followed a parallel time course. A same type of behaviour was found in the time trends of each individual age-group. The data from most countries revealed similar temporal patterns. Conclusions The relationships between the temporal changes of mortality from Crohn's disease and ulcerative colitis might suggest the presence of one primary risk factor responsible for the occurrence of both diseases, and at the existence of one additional secondary risk factor, responsible for the expression of Crohn's disease alone. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 21 TC 19 Z9 19 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2007 VL 36 IS 4 BP 890 EP 899 DI 10.1093/ije/dym034 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 218XW UT WOS:000250050300034 PM 17420164 ER PT J AU Tzika, AA Astrakas, L Cao, HH Mintzopoulos, D Andronesi, OC Mindrinos, M Zhang, JW Rahme, LG Blekas, KD Likas, AC Galatsanos, NP Carroll, RS Black, PM AF Tzika, A. Aria Astrakas, Loukas Cao, Haihui Mintzopoulos, Dionyssios Andronesi, Ovidiu C. Mindrinos, Michael Zhang, Jiangwen Rahme, Laurence G. Blekas, Konstantinos D. Likas, Aristidis C. Galatsanos, Nikolas P. Carroll, Rona S. Black, Peter M. TI Combination of high-resolution magic angle spinning proton magnetic resonance spectroscopy and microscale genomics to type brain tumor biopsies SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE brain/CNS cancers; tumor biomarkers; anaplastic ganglioglioma; ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy; genomics ID CHOLINE PHOSPHOLIPID-METABOLISM; MAMMARY EPITHELIAL-CELLS; IN-VIVO; NMR-SPECTROSCOPY; GENE-EXPRESSION; IMAGING BIOMARKERS; KINASE INHIBITORS; BREAST-CANCER; SPECTRA; QUANTIFICATION AB Advancements in the diagnosis and prognosis of brain tumor patients, and thus in their survival and quality of life, can be achieved using biomarkers that facilitate improved tumor typing. We introduce and implement a combinatorial metabolic and molecular approach that applies state-of-the-art, high-resolution magic angle spinning (HRMAS) proton (H-1) MRS and gene transcriptome profiling to intact brain tumor biopsies, to identify unique biomarker profiles of brain tumors. Our results show that samples as small as 2 mg can be successfully processed, the HRMAS H-1 MRS procedure does not result in mRNA degradation, and minute mRNA amounts yield high-quality genomic data. The MRS and genomic analyses demonstrate that CNS tumors have altered levels of specific H-1 MRS metabolites that directly correspond to altered expression of Kennedy pathway genes; and exhibit rapid phospholipid turnover, which coincides with upregulation of cell proliferation genes. The data also suggest Sonic Hedgehog pathway (SHH) dysregulation may play a role in anaplastic ganglioglioma pathogenesis. That a strong correlation is seen between the HRMAS H-1 MRS and genomic data cross-validates and further demonstrates the biological relevance of the MRS results. Our combined metabolic/molecular MRS/genomic approach provides insights into the biology of anaplastic ganglioglioma and a new potential tumor typing methodology that could aid neurologists and neurosurgeons to improve the diagnosis, treatment, and ongoing evaluation of brain tumor patients. C1 Harvard Univ, Sch Med, Dept Surg, NMR Surg Lab, 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. Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Surg, Lab Mol Surg, Boston, MA 02114 USA. Univ Ioannina, Dept Comp Sci, GR-45110 Ioannina, Greece. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Dept Surg, NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu RI Astrakas, Loukas/F-5918-2011; Zhang, Jiangwen/A-7654-2013 NR 38 TC 39 Z9 39 U1 0 U2 5 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD AUG PY 2007 VL 20 IS 2 BP 199 EP 208 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 193OG UT WOS:000248282800009 PM 17611638 ER PT J AU Haroutunian, V Davis, KL AF Haroutunian, Vahrant Davis, Kenneth L. TI Introduction to the Special Section: Myelin and oligodendrocyte abnormalities in schizophrenia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material DE gene expression; microarray; neuroanatomy; neuropathology; post-mortem; schizophrenia ID PREFRONTAL CORTEX; GENE-EXPRESSION; MOOD DISORDERS; DYSFUNCTION; NEUROPATHOLOGY; POSTMORTEM; DENSITY; MATTER AB A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, Room 4F-33A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH064673, MH066392] NR 25 TC 28 Z9 28 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD AUG PY 2007 VL 10 IS 4 BP 499 EP 502 DI 10.1017/S1461145706007449 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 189BM UT WOS:000247963500006 PM 17583597 ER PT J AU Gelber, RP Kurth, T Manson, JE Buring, JE Gaziano, JM AF Gelber, R. P. Kurth, T. Manson, J. E. Buring, J. E. Gaziano, J. M. TI Body mass index and mortality in men: evaluating the shape of the association SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body mass index; mortality; epidemiology; bias ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; PROSPECTIVE COHORT; PHYSICIANS HEALTH; RISK-FACTORS; US ADULTS; FOLLOW-UP; WEIGHT; WOMEN; OVERWEIGHT AB Objective: Controversy regarding the relationship between body mass index (BMI) and mortality continues to exist. Most of the previous studies have not comprehensively accounted for major sources of bias. We examined the association between BMI and all-cause mortality according to pre-existing disease and smoking status in a large prospective cohort. Methods: Participants were 99 253 male physicians in the Physicians' Health Study enrollment cohort (40-84 years) who provided self-reported information in 1982. We used Cox proportional hazards regression to examine the association between baseline BMI and mortality. Results: A total of 5438 men died (median follow-up, 5.7 years). Although a U-shaped association between BMI and all-cause mortality was seen among all men, we found a linear relationship when accounting for potential sources of bias. In the optimal model excluding men who died within 2 years, and adjusting for age, smoking, alcohol consumption, physical activity, prior disease and interactions between BMI and prior disease, and between BMI and smoking, those with BMI < 20.0 kg/m(2) had a relative risk (RR) of death of 0.88 (95% confidence interval (CI), 0.56-1.40), as compared to men with BMI 22.5-24.9 kg/m(2). By contrast, men with BMI 30.0-34.9 kg/m(2) had an RR of 1.45 (95% CI, 1.10-1.91) and those with BMI >= 35.0 kg/m(2) had an RR of 1.62 (95% CI, 1.12-2.35; P for linear trend, < 0.001). According to WHO categories, men in the 'overweight' range (BMI 25.0-29.9 kg/m(2)) had an RR of 1.20 (95% CI, 1.05-1.38) as compared to men in the 'normal' range (BMI < 25.0kg/m(2)). Conclusions: In this large, prospective cohort, we found a consistent linear association between higher BMI and increased risk of mortality after accounting for several potential sources of bias, even among those within the 'overweight' range of BMI. Public health messages should emphasize the preponderance of evidence supporting the adverse health effects associated with higher body weight. C1 Harvard Univ, Dept Med, Div Aging, Brigham & Womens Hosp,Sch Med, Boston, MA 02120 USA. Harvard Univ, Dept Med, Div Prevent Med, Brigham & Womens Hosp,Sch Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Kurth, T (reprint author), Harvard Univ, Dept Med, Div Aging, Brigham & Womens Hosp,Sch Med, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA34944, CA40360, R01 CA097193]; NHLBI NIH HHS [HL26490, HL34595] NR 33 TC 33 Z9 35 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD AUG PY 2007 VL 31 IS 8 BP 1240 EP 1247 DI 10.1038/sj.ijo.0803564 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 195WN UT WOS:000248443100006 PM 17342077 ER PT J AU Boseley, ME Hartnick, CJ AF Boseley, Mark E. Hartnick, Christopher J. TI A useful algorithm for managing the difficult pediatric airway SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE difficult pediatric; airway; tracheal stenosis; subglottic stenosis; stridor AB Management of the pediatric airway can be extremely challenging. A useful algorithm is presented that can be used when faced with even the most difficult of airways. A new adjuvant airway tool is also presented, as well as a list of equipment for the operating room. We will attempt to emphasize key points while presenting a patient that we have recently treated. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Madigan Army Med Ctr, Tacoma, WA 98431 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Boseley, ME (reprint author), Madigan Army Med Ctr, Bldg 9040 Fitzsimmons Dr, Tacoma, WA 98431 USA. EM mboseley@comcast.net; Christopher_hartnick@meei.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 0 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 AUG PY 2007 VL 71 IS 8 BP 1317 EP 1320 DI 10.1016/j.ijporl.2007.05.009 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 196ZH UT WOS:000248521700024 PM 17573122 ER PT J AU Allen, AM Den, R Wong, JS Zurakowski, D Soto, R Janne, PA Zellos, L Bueno, R Sugarbaker, DJ Baldini, EH AF Allen, Aaron M. Den, Robert Wong, Julia S. Zurakowski, David Soto, Ricardo Janne, Pasi A. Zellos, Lambros Bueno, Raphael Sugarbaker, David J. Baldini, Elizabeth H. TI Influence of radiotherapy technique and dose on patterns of failure for mesothelioma patients after extrapleural pneumonectomy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE mesothelioma; radiotherapy; extrapleural pneumonectomy ID MALIGNANT PLEURAL MESOTHELIOMA; MULTICENTER PHASE-II; HEMITHORACIC RADIATION; TRIMODALITY THERAPY; LUNG-CANCER; CISPLATIN; TRIAL; GEMCITABINE; MANAGEMENT; RESECTION AB Purpose: Extrapleural pneumonectomy (EPP) is an effective treatment of malignant pleural mesothelioma. We compared the outcomes after moderate-dose hemithoracic radiotherapy (MDRT) and high-dose hemithoracic RT (HDRT) after EPP for malignant pleural mesothelioma. Methods and Materials: Between July 1994 and April 2004, 39 patients underwent EPP and adjuvant RT at Dana-Farber-Cancer Institute/Brigham and Women's Hospital. Between 1994 and 2002, MDRT, including 30 Gy to the hemithorax, 40 Gy to the mediastinum, and boosts to positive margins or nodes to 54 Gy, was given, generally with concurrent chemotherapy. In 2003, HDRT to 54 Gy with a matched photon/electron technique was given, with sequential chemotherapy. Results: A total of 39 patients underwent RT after EPP. The median age was 59 years (range, 44-77). The histologic type was epithelial in 25 patients (64 %) and mixed or sarcomatoid in 14 patients (36 %). Of the 39 patients, 24 underwent MDRT and 15 (39 %) HDRT. The median follow-up was 23 months (range, 6-71). The median overall survival was 19 months (95% confidence interval, 14-24). The median time to distant failure (DF) and local failure (LF) was 20 months (95% confidence interval, 14-26) and 26 months (95% confidence interval, 16-36), respectively. On univariate and multivariate analyses, only a mixed histologic type was predictive of inferior DF (p < 0.006) and overall survival (p < 0.004). The RT technique was not predictive of LF, DF, or overall survival. The LF rate was 50 % (12 of 24) after MDRT and 27 % (4 of 15) after HDRT (P = NS). Four patients who had undergone HDRT were alive and without evidence of disease at the last follow-up. Conclusions: High-dose hemithoracic RT appears to limit in-field LF compared with MDRT. However, DF remains a significant challenge, with one-half of our patients experiencing DF. (c) 2007 Elsevier Inc. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Childrens Hosp, Harvard Med Sch, Dept Orthoped Surg, Boston, MA 02115 USA. Childrens Hosp, Harvard Med Sch, Dept Biostat, Boston, MA 02115 USA. RP Allen, AM (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM aallen@lroc.harvard.edu NR 18 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2007 VL 68 IS 5 BP 1366 EP 1374 DI 10.1016/j.ijrobp.2007.02.047 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 198LK UT WOS:000248629400011 PM 17674974 ER PT J AU Kozak, KR Kachnic, LA Adams, J Crowley, EM Alexander, BM Mamon, HJ Fernandez-Del Castillo, C Ryan, DP DeLaney, TF Hong, TS AF Kozak, Kevin R. Kachnic, Lisa A. Adams, Judith Crowley, Elizabeth M. Alexander, Brian M. Mamon, Harvey J. Fernandez-Del Castillo, Carlos Ryan, David P. DeLaney, Thomas F. Hong, Theodore S. TI Dosimetric feasibility of hypofractionated proton radiotherapy for neoadjuvant pancreatic cancer treatment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE dosimetric comparison; IMRT; neoadjuvant therapy; pancreatic cancer; protons ID INTENSITY-MODULATED RADIOTHERAPY; SMALL-BOWEL TOXICITY; RECTAL-CANCER; RADIATION-THERAPY; PREOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; STEREOTACTIC RADIOSURGERY; CURATIVE RESECTION; PHASE-II; ADENOCARCINOMA AB Purpose: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Methods and Materials: The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (<= 20% prescribed dose for both kidneys and <= 60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. Conclusions: A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA USA. Med Ctr, Dept Radiat Oncol, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX-3, Boston, MA 02114 USA. EM tshong1@partners.org NR 39 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2007 VL 68 IS 5 BP 1557 EP 1566 DI 10.1016/j.ijrobp.2007.02.056 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 198LK UT WOS:000248629400035 PM 17544599 ER PT J AU Lin, NU Parker, LM Come, SE Burstein, HJ Haldoupis, M Ryabin, N Gelman, R Winer, EP Shulman, LN AF Lin, Nancy U. Parker, Leroy M. Come, Steven E. Burstein, Harold J. Haldoupis, Margaret Ryabin, Nicole Gelman, Rebecca Winer, Eric P. Shulman, Lawrence N. TI Phase II study of CT-2103 as first- or second-line chemotherapy in patients with metastatic breast cancer: unexpected incidence of hypersensitivity reactions SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE metastatic breast cancer; CT-2103; Xyotax; taxanes ID EUROPEAN ORGANIZATION; 3-HOUR INFUSION; PACLITAXEL; TRIAL; DOCETAXEL; CARBOPLATIN; DOXORUBICIN; MULTICENTER; TAXOL AB This study evaluated the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with HER2-negative, metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Although CT-2103 had activity in this small study, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected, and led to early termination of the trial. Purpose To evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Patients and Methods Eighteen women with HER2-negative breast cancer were enrolled. Patients received intravenous CT-2103 at a dose of 175 mg/m(2) of conjugated paclitaxel over 10 min every 3 weeks, without routine premedication. Eighty-three percent of women had received prior chemotherapy as part of adjuvant (39%), metastatic (17%), or both adjuvant and metastatic (28%) treatment. Three patients (17%) had previously received a taxane in the adjuvant setting. Results Objective responses were observed in 4 of 18 patients (overall response rate, 22%, 95% confidence interval, 6 to 48%). Grade 3 or 4 neuropathy was observed in four patients. Grade 3 or 4 hypersensitivity reactions (HSR) were observed in four patients; none occurred prior to cycle 4 of therapy. Because of the higher-than-expected rate of HSR, the study was terminated early. Conclusion Although CT-2103 had activity in this small study of women with HER2-negative metastatic breast cancer, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected. Hypersensitivity reactions were most likely to occur in later cycles of treatment, suggesting a true drug allergy, distinct from the HSR typically seen with standard paclitaxel. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lnshulman@partners.org FU NCI NIH HHS [T32 CA009172] NR 23 TC 21 Z9 22 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 2007 VL 25 IS 4 BP 369 EP 375 DI 10.1007/s10637-007-9034-y PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 179FR UT WOS:000247275600010 PM 17345004 ER PT J AU Maki, JL Nesti, HA Shetty, RK Rhee, DJ AF Maki, Jesse L. Nesti, Heather A. Shetty, Rajesh K. Rhee, Douglas J. TI Transcorneal tube extrusion in a child with a Baerveldt glaucoma drainage device SO JOURNAL OF AAPOS LA English DT Article ID IMPLANT AB We describe a clinical scenario in which a child was treated for glaucoma and aqueous misdirection with surgical placement of a tube shunt. The child then suffered extrusion of the tube through the cornea, a rare complication of such procedures. This complication has only been seen in children, and thus, young patients with tube shunts need careful and frequent monitoring, especially during the first year of the post tube shunt period to ensure that they have not developed this complication. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Mayo Clin, Jacksonville, FL 32224 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@ao1.com NR 4 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD AUG PY 2007 VL 11 IS 4 BP 395 EP 397 DI 10.1016/j.jaapos.2006.12.057 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 201IL UT WOS:000248824600016 PM 17409000 ER PT J AU Otto, MW Teachman, BA Cohen, LS Soares, CN Vitonis, AF Harlow, BL AF Otto, Michael W. Teachman, Bethany A. Cohen, Lee S. Soares, Claudio N. Vitonis, Allison F. Harlow, Bernard L. TI Dysfunctional attitudes and episodes of major depression: Predictive validity and temporal stability in never-depressed, depressed, and recovered women SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE depression; dysfunctional attitudes; cognitive vulnerability; depressive scarring ID STRESSFUL LIFE EVENTS; COGNITIVE ASSESSMENT; UNIPOLAR DEPRESSION; NEGATIVE COGNITION; FOLLOW-UP; SYMPTOMS; VULNERABILITY; DISORDER; RELAPSE; THERAPY AB In a large, community-based sample of women (N = 750), the authors examined the nature of associations between dysfunctional attitudes and depression. Dysfunctional attitudes were evaluated both as a vulnerability factor for depression and as a consequence of depression. A link was found between past depression and baseline elevations in dysfunctional attitudes that was independent of current subsyndromal symptoms, but intensification of dysfunctional attitudes following prospectively evaluated episodes of depression (depressive "scarring") was not observed. Although baseline dysfunctional attitudes predicted an episode of major depression over 3 years of prospective study, this prediction, considered alone or in interaction with negative life events, was redundant with that offered by history of past depression. Further, no significant prediction was evident for the Dysfunctional Attitude Scale (A. N. Weissman & A. T. Beck, 1978) when the formerly depressed and never-depressed cohorts were considered separately. Implications for cognitive theories are discussed. C1 Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA. Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM mwotto@bu.edu FU NIMH NIH HHS [R01-MH-50013] NR 62 TC 38 Z9 39 U1 0 U2 20 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2007 VL 116 IS 3 BP 475 EP 483 DI 10.1037/0021-843X.116.3.475 PG 9 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 198QO UT WOS:000248642800004 PM 17696703 ER PT J AU Taft, CT Kaloupek, DG Schumm, JA Marshall, AD Panuzio, J King, DW Keane, TM AF Taft, Casey T. Kaloupek, Danny G. Schumm, Jeremiah A. Marshall, Amy D. Panuzio, Jillian King, Daniel W. Keane, Terence M. TI Posttraumatic stress disorder symptoms, physiological reactivity, alcohol problems, and aggression among military veterans SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; aggression; physiological reactivity; alcohol; hyperarousal ID VIETNAM COMBAT VETERANS; PARTNER VIOLENCE; PSYCHOLOGICAL DISTRESS; CAGE QUESTIONNAIRE; COGNITIVE CONTROL; FIT INDEXES; BEHAVIOR; RESPONSES; EXPOSURE; ASSAULT AB This study examined the association between posuraumatic stress disorder (PTSD) symptomatology and aggressive behavior among a sample of male Vietnam veterans (N = 1,328). Results indicated that the hyperarousal PTSD symptom cluster evidenced the strongest positive association with aggression at the bivariate level when compared with the other PTSD symptom clusters. When the PTSD symptom clusters were examined together as predictors, hyperarousal symptoms evidenced a significant positive relationship with aggression, and avoidance/numbing symptoms were negatively associated with aggression. Examination of potential mediators indicated that hyperarousal symptoms were directly associated with aggression and indirectly related to aggression via alcohol problems. Reexperiencing symptoms were associated with aggression only indirectly and through their positive association with physiological reactivity and negative association with alcohol problems. Study results highlight the complexity of the relationship between PTSD symptoms and aggression, and suggest possible mechanisms explaining this association. C1 Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Taft, CT (reprint author), Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov OI Kaloupek, Danny/0000-0002-0795-593X NR 75 TC 111 Z9 112 U1 10 U2 23 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2007 VL 116 IS 3 BP 498 EP 507 DI 10.1037/0021-843X.116.3.498 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 198QO UT WOS:000248642800007 PM 17696706 ER PT J AU Joiner, TE Cook, JM Hersen, M Gordon, KH AF Joiner, Thomas E., Jr. Cook, Joan M. Hersen, Michel Gordon, Kathryn H. TI Double depression in older adult psychiatric outpatients: Hopelessness as a defining feature SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE double depression; hopelessness; older adults; dysthymia; major depression ID PSYCHOMETRIC PROPERTIES; MAJOR DEPRESSION; INVENTORY; ANXIETY AB Background: There is a paucity of research on the distinguishing features of double depression, particularly in older adults. Preliminary studies have revealed that individuals with double depression diagnoses tend to have more severe depression than individuals with major depression or dysthymia alone, but few other distinctions between the diagnostic categories have been found. Method: We examined the possibility that hopelessness particularly characterizes double depression, by comparing older adults with double depression, dysthymia alone, or major depression alone, on hopelessness, as well as on internal and external locus of control. The sample included 54 older psychiatric outpatients who completed a battery of cognitive and symptom measures, and underwent structured clinical interviews. Results: Double depressed patients showed high levels of hopelessness, whereas patients with either major depression or dysthymia alone showed more moderate levels of hopelessness. Low internal locus of control characterized both groups with a dysthymia diagnosis (dysthymia alone and double depression), and differentiated them from the group with major depression alone. Limitations: The sample size was modest, and the results may not generalize to older adults with different demographic characteristics. Conclusions: Hopelessness may be important in understanding the phenomenology of double depression in older adults, and may inform diagnostics and psychotherapeutics as well. (c) 2007 Elsevier B.V. All rights reserved. C1 Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Pacific Univ, Sch Profess Psychol, Forest Grove, OR USA. RP Joiner, TE (reprint author), Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. EM joiner@psy.fsu.edu NR 18 TC 8 Z9 10 U1 1 U2 2 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 AUG PY 2007 VL 101 IS 1-3 BP 235 EP 238 DI 10.1016/j.jad.2005.03.019 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 187PJ UT WOS:000247860000025 PM 17475340 ER PT J AU McElroy, SL Suppes, T Frye, MA Altshuler, LL Stanford, K Martens, B Leverich, GS Post, RM Keck, PE AF McElroy, Susan L. Suppes, Trisha Frye, Mark A. Altshuler, Lori L. Stanford, Kevin Martens, Brian Leverich, Gabriele S. Post, Robert M. Keck, Paul E., Jr. TI Open-label aripiprazole in the treatment of acute bipolar depression: A prospective pilot trial SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE aripiprazole; bipolar; depression; akathisia ID PLACEBO-CONTROLLED TRIAL; ATYPICAL ANTIPSYCHOTICS; DOUBLE-BLIND; II DEPRESSION; RATING-SCALE; WEIGHT-GAIN; DISORDER; MANIA; TOLERABILITY; PRAMIPEXOLE AB Background: Increasing evidence indicates that some second-generation antipsychotics are efficacious in bipolar depression, but there are few data on this illness for the novel agent aripiprazole. Methods: Aripiprazole response was prospectively assessed for 8 weeks with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with acute depression inadequately responsive to 1 mood stabilizer. Side effects and body weight were also evaluated. Outcome measures were analyzed with repeated measures ANOVAs. Results: Patients showed a significant decrease in mean MADRS total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8-week-trial. Thirteen (42%) patients met criteria for response (>= 50% reduction in MADRS total score), 11 (35%)patients met criteria for remission (final MADRS total score <= 12), and 9 (29%) patients discontinued aripiprazole for side effects, most commonly akathisia (N=4). As a group, patients showed statistically insignificant weight gain (0.8 +/- 2.5 kg) over the 8-week trial. Conclusion: Aripiprazole was associated with beneficial effects on mood in some patients with bipolar depression, but also had a high discontinuation rate, primarily due to side effects. Double-blind, placebo-controlled studies are necessary to determine aripiprazole's efficacy, tolerability, and safety in bipolar depression. (c) 2007 Published by Elsevier B.V. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45267 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. NIMH, Biol Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, POB 670559,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM susan.mcelroy@uc.edu NR 37 TC 28 Z9 31 U1 2 U2 2 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 AUG PY 2007 VL 101 IS 1-3 BP 275 EP 281 DI 10.1016/j.jad.2006.11.025 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 187PJ UT WOS:000247860000033 PM 17229469 ER PT J AU Ly, NP Celedon, JC AF Ly, Ngoc P. Celedon, Juan C. TI Family history, environmental exposures in early life, and childhood asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID ATOPY; CHILDREN; RISK C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulmonary Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Celedon, JC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM juan.celedon@channing.harvard.edu FU NHLBI NIH HHS [HL073373, HL66289, HL079966] NR 16 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2007 VL 120 IS 2 BP 271 EP 272 DI 10.1016/j.jaci.2007.05.045 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 198VF UT WOS:000248654900006 PM 17666215 ER PT J AU Raby, BA Klanderman, B Murphy, A Mazza, S Camargo, CA Silverman, EK Weiss, ST AF Raby, Benjamin A. Klanderman, Barbara Murphy, Amy Mazza, Salvatore Camargo, Carlos A., Jr. Silverman, Edwin K. Weiss, Scott T. TI A common mitochondrial haplogroup is associated with elevated total serum IgE levels SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE mitochondria; haplogroup; genetics; asthma; atopy; immunoglobulin E; atopic dermatitis; single nucleotide polymorphism; susceptibility ID MATERNAL HISTORY; CHILDHOOD ASTHMA; EUROPEAN MTDNAS; EARLY-LIFE; DNA; POPULATION; DISEASE; CHILDREN; GENOME; ECZEMA AB Background: Maternal history of asthma or atopy is among the most consistently reported risk factors for asthma and atopy in children, yet the molecular basis for this observation remains unclear. Mitochondria are inherited exclusively through the maternal line, raising the possibility that sequence variation in the mitochondrial genome contributes to the pathogenesis of asthma and atopy. Objective: We set out to determine whether common European mitochondrial haplogroups are associated with asthma-related atopic phenotypes. Methods: We studied 654 self-reported white children age 5 to 12 years with mild to moderate asthma participating in the Childhood Asthma Management Program. Eight haplogroup-tagging polymorphisms were genotyped with TaqMan probe hybridization assays, and mitochondrial haplogroup tests of association with asthma-related and atopy-related phenotypes were performed with haplo.stats. Results: We found significant evidence of mitochondrial haplogroup association with total serum IgE levels (global significance, P = .04), with carriers of European haplogroup U (frequency 11%) having higher total serum IgE levels (median level, 684 lU/L) compared with noncarriers (389 IU/L; P = .001). Haplogroup U carriers also had trends of greater skin prick test reactivity (P = .03) and higher frequency of atopic dermatitis (P = .07), although global haplogroup tests for these later 2 phenotypes were not significant at an alpha level of 0.05. Conclusion: These data are the first to suggest that common mitochondrial haplogroups influence the atopic diathesis. Clinical implications: These findings may provide a molecular explanation for the prominent influence of maternal history of atopy on the development of atopy in offspring. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. RP Raby, BA (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. EM benjamin.raby@channing.harvard.edu RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NHLBI NIH HHS [K08 HL074193, N01-HR-16049, P50 HL67664, T32 HL07427] NR 43 TC 39 Z9 39 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2007 VL 120 IS 2 BP 351 EP 358 DI 10.1016/j.jaci.2007.05.029 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 198VF UT WOS:000248654900020 PM 17666217 ER PT J AU Lipsky, BA Giordan, P Choudhri, S Song, J AF Lipsky, Benjamin A. Giordan, Philip Choudhri, Shurjeel Song, James TI Treating diabetic foot infections with sequential intravenous to oral moxifloxacin compared with piperacillin-tazobactam/amoxicillin-clavulanate SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 46th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 27-30, 2006 CL San Francisco, CA DE complicated skin and skin structure infections; fluoroquinolones; penicillins; beta-lactam inhibitors ID IN-VITRO ACTIVITY; SOFT-TISSUE INFECTIONS; SKIN-STRUCTURE INFECTIONS; OPEN-LABEL TRIAL; COMPLICATED SKIN; AMOXICILLIN-CLAVULANATE; ANTIMICROBIAL AGENTS; ANAEROBIC-BACTERIA; MULTICENTER TRIAL; FLUOROQUINOLONES AB Objectives: Complicated skin and skin structure infections (cSSSIs), including diabetic foot infections (DFIs), are often polymicrobial, requiring combination or broad-spectrum therapy. Moxifloxacin, a broad-spectrum fluoroquinolone, is approved for cSSSI and can be administered by either intravenous (iv) or oral routes. To assess the efficacy of moxifloxacin for treating DFIs, we analysed a subset of patients with these infections who were enrolled in a prospective, double-blind study that compared the efficacy of moxifloxacin with piperacillin-tazobactam and amoxicillin-clavulanate. Methods: Patients >= 18 years of age with a DFI requiring initial iv therapy were randomized to either moxifloxacin (400 mg/day) or piperacillin-tazobactam (3.0/0.375 g every 6 h) for at least 3 days followed by moxifloxacin (400 mg/day orally) or amoxicillin-clavulanate (800 mg every 12 h orally), if appropriate, for 7-14 days. DFI was usually defined as any foot infection plus a history of diabetes. Our primary efficacy outcome was the clinical response of the infection at test-of-cure (TOC), 10-42 days post-therapy. Results: Among 617 patients enrolled in the original study, 78 with DFIs were evaluable for treatment efficacy. Clinical cure rates at TOC were similar for moxifloxacin and piperacillin-tazobactam/ amoxicillin-clavulanate (68% versus 61%) for patients with investigator-defined infection (P = 0.54). Overall pathogen eradication rates in the microbiologically-valid population were 69% versus 66% for moxifloxacin and comparator, respectively (P = 1.00). Conclusions: Intravenous +/- oral moxifloxacin was as effective as iv piperacillin-tazobactam +/- amoxicillin-clavulanate in treating moderate-to-severe DFIs. Moxifloxacin may have potential as a monotherapy regimen for DFIs. C1 Univ Washington, Seattle, WA 98195 USA. Orlando Reg Med Ctr Inc, Orlando, FL USA. Bayer Healthcare, West Haven, CT USA. Replidyne, Milford, MA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM benjamin.lipsky@med.va.gov RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 35 TC 45 Z9 45 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD AUG PY 2007 VL 60 IS 2 BP 370 EP 376 DI 10.1093/jac/dkm130 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 203PM UT WOS:000248986500023 PM 17553812 ER PT J AU Bamman, MM AF Bamman, Marcas M. TI Take two NSAIDs and call on your satellite cells in the morning SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material ID SKELETAL-MUSCLE; RESISTANCE EXERCISE; CARDIAC MYOCYTES; HYPERTROPHY C1 Univ Alabama, Dept Physiol & Biophys, Birmingham, W Midlands, England. Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. RP Bamman, MM (reprint author), Univ Alabama, Dept Physiol & Biophys, Birmingham, W Midlands, England. EM mbamman@uab.edu NR 13 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2007 VL 103 IS 2 BP 415 EP 416 DI 10.1152/japplphysiol.00536.2007 PG 2 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 196CP UT WOS:000248459600001 PM 17525294 ER PT J AU Winkler, T Venegas, JG AF Winkler, Tilo Venegas, Jose G. TI Complex airway behavior and paradoxical responses to bronchoprovocation SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE asthma; bronchoconstriction; airway hyperresponsiveness; dynamic equilibrium; complex systems ID RESOLUTION COMPUTED-TOMOGRAPHY; SELF-ORGANIZED PATCHINESS; SMOOTH-MUSCLE; LUNG-VOLUME; INTRAVENOUS HISTAMINE; TIDAL VOLUME; IN-VIVO; INDUCED BRONCHOCONSTRICTION; BIMODAL VENTILATION; CATASTROPHIC SHIFTS AB Heterogeneity of airway constriction and regional ventilation in asthma are commonly studied under the paradigm that each airway's response is independent from other airways. However, some paradoxical effects and contradictions in recent experimental and theoretical findings suggest that considering interactions among serial and parallel airways may be necessary. To examine airway behavior in a bronchial tree with 12 generations, we used an integrative model of bronchoconstriction, including for each airway the effects of pressure, tethering forces, and smooth muscle forces modulated by tidal stretching during breathing. We introduced a relative smooth muscle activation factor ( T-r) to simulate increasing and decreasing levels of activation. At low levels of T-r, the model exhibited uniform ventilation and homogeneous airway narrowing. But as T-r reached a critical level, the airway behavior suddenly changed to a dual response with a combination of constriction and dilation. Ventilation decreased dramatically in a group of terminal units but increased in the rest. A local increase of T-r in a single central airway resulted in full closure, while no central airway closed under global elevation of T-r. Lung volume affected the response to both local and global stimulation. Compared with imaging data for local and global stimuli, as well as for the time course of airway lumen caliber during bronchoconstriction recovery, the model predictions were similar. The results illustrate the relevance of dynamic interactions among serial and parallel pathways in airway interdependence, which may be critical for the understanding of pathological conditions in asthma. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02114 USA. RP Winkler, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM twinkler@vqpet.mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [HL-68011] NR 42 TC 46 Z9 49 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2007 VL 103 IS 2 BP 655 EP 663 DI 10.1152/japplphysiol.00041.2007 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 196CP UT WOS:000248459600035 PM 17478609 ER PT J AU Emery, MJ Eveland, RL Kim, SS Hildebrandt, J Swenson, ER AF Emery, Michael J. Eveland, Randy L. Kim, Seong S. Hildebrandt, Jacob Swenson, Erik R. TI CO2 relaxes parenchyma in the liquid-filled rat lung SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE alveolar; pulmonary mechanics; ventilation-to-perfusion matching ID MECHANICAL-PROPERTIES; VENTILATION; PERFUSION; HYPOXIA; TISSUE; DOGS; HETEROGENEITY; DISSOCIATION; RESISTANCE; HYPEROXIA AB CO2 regulation of lung compliance is currently explained by pH- and CO2-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation ( V. A) to perfusion ( Q.). Twenty adult rats were slowly ventilated with modified Krebs solution ( rate = 3 min(-1), 37 degrees C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O-2, balance N-2, and CO2 varied to produce alveolar hypocapnia ( PCO2 = 26.1 +/- 2.4 mmHg, pH = 7.56 +/- 0.04) or hypercapnia ( PCO2 = 55.0 +/- 2.3 mmHg, pH = 7.23 +/- 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced similar to 30% when exposed to hypercapnia vs. hypocapnia ( P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO2 from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO2 effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO2, is independent of ( and apparently in parallel with) passive tissue elements and may actively contribute to V-A/Q. matching. C1 VA Puget Sound Hlth Care Syst, Pulm & Crit Care Med, Dept Vet Affairs, Seattle, WA 98108 USA. Washington Univ, Dept Physiol, Sch Med, St Louis, MO 63130 USA. Washington Univ, Dept Biophys, Sch Med, St Louis, MO 63130 USA. Washington Univ, Dept Med Pulm & Crit Care Med, Sch Med, St Louis, MO 63130 USA. RP Emery, MJ (reprint author), VA Puget Sound Hlth Care Syst, Pulm & Crit Care Med, Dept Vet Affairs, S-111-PULM,1660 S Columbian Way, Seattle, WA 98108 USA. EM mjemery@u.washington.edu FU NHLBI NIH HHS [HL-24163] NR 33 TC 8 Z9 8 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2007 VL 103 IS 2 BP 710 EP 716 DI 10.1152/japplphysiol.00128.2006 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 196CP UT WOS:000248459600041 PM 17495121 ER PT J AU Winter, JO Cogan, SF Rizzo, JF AF Winter, Jessica O. Cogan, Stuart F. Rizzo, Joseph F., III TI Retinal prostheses: current challenges and future outlook SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Review DE visual prosthesis; retina; biocompatibility; electrode ID HIGH STIMULUS RATES; SUBRETINAL ELECTRICAL-STIMULATION; SEMICONDUCTOR-BASED PHOTODIODES; OPTICAL COHERENCE TOMOGRAPHY; CHARGE INJECTION LIMITS; RETINITIS-PIGMENTOSA; VISUAL-PERCEPTION; AUDITORY-NERVE; RABBIT RETINA; PERFORATED MEMBRANE AB Blindness from retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), usually causes a significant decline in quality of life for affected patients. Currently there is no cure for these conditions. However, over the last decade, several groups have been developing retinal prostheses which hopefully will provide some degree of improved visual function to these patients. Several such devices are now in clinical trials. Unfortunately, the possibility of electrode or tissue damage limits excitation schemes to those that may be employed with electrodes that have relatively low charge densities. Further, the excitation thresholds that have been required to achieve vision to date, in general, are relatively high. This may result in part from poor apposition between neurons and the stimulating electrodes and is confounded by the effects of the photoreceptor loss, which initiates other pathology in the surviving retinal tissue. The combination of these and other factors imposes a restriction on the pixel density that can be used for devices that actively deliver electrical stimulation to the retina. The resultant use of devices with relatively low pixel densities presumably will limit the degree of visual resolution that can be obtained with these devices. Further increases in pixel density, and therefore increased visual acuity, will necessitate either improved electrode-tissue biocompatibility or lower stimulation thresholds. To meet this challenge, innovations in materials and devices have been proposed. Here, we review the types of retinal prostheses investigated, the extent of their current biocompatibility and future improvements designed to surmount these limitations. C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA. EIC Labs, Norwood, MA 02062 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Winter, JO (reprint author), VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. EM winter.63@osu.edu NR 138 TC 62 Z9 66 U1 0 U2 28 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0920-5063 EI 1568-5624 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PD AUG PY 2007 VL 18 IS 8 BP 1031 EP 1055 DI 10.1163/156856207781494403 PG 25 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 203WS UT WOS:000249005300007 PM 17705997 ER PT J AU Tang, SQ Vickers, SM Hsu, HP Spector, M AF Tang, Shunqing Vickers, Scott M. Hsu, Hu-Ping Spector, Myron TI Fabrication and characterization of porous hyaluronic acid-collagen composite scaffolds SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE hyaluronan; hyaluronic acid; type I collagen; scaffold; chondrogenesis; cartilage tissue engineering ID CROSS-LINKING; DRUG-DELIVERY; TISSUE; CHONDROCYTES; MATRIX; BIOCOMPATIBILITY; REGENERATION; HYDROGELS; SKIN; GELS AB Hyaluronic acid (HA) plays a vital role in many tissues, influencing water content and mechanical function, and has been shown to have positive biological effects on cell behavior in vitro. To begiii to determine whether these benefits can be accessed if HA is incorporated into collagen-based scaffolds for tissue engineering, HA-collagen composite matrices were prepared and selected properties evaluated. HA-collagen scaffolds were cross-linked with carbodiimide and loss rates of HA in culture medium assessed. Scaffold pore structures were evaluated by light and electron microscopy. Adult canine chondrocytes were grown in selected HA-collagen scaffolds to assess the effects of HA on cell behavior. Homogenous HA-collagen slurries were achieved when polyionic complexes were suppressed. HA was uniformly distributed through the scaffolds, which demonstrated honeycomb-like pores with interconnectivity among pores increasing as HA content increased. Virtually all of the HA added to the collagen slurry was incorporated into the composite scaffolds that underwent a 7-day cross-linking protocol. After 5 days in culture medium, the HA content in the scaffolds was 5-7% regardless of initial HA loading. After only 2 weeks in culture cartilaginous tissue was found in the chondrocyte-seeded HA-collagen scaffolds. This study contributes to the understanding of the effects of HA content, pH, and cross-link treatment on pore characteristics and degradation behavior essential for the design of HA-collageu scaffolds. The demonstration that these scaffolds can be populated by chondrocytes and support hi vitro formation of cartilaginous tissue warrants further investigation of this material system for tissue engineering. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res 82A: 323-335, 2007 C1 Jinan Univ, Dept Biomed Engn, Guangzhou 510632, Peoples R China. VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Spector, M (reprint author), Jinan Univ, Dept Biomed Engn, Guangzhou 510632, Peoples R China. EM mspector@rics.bwh.harvard.edu NR 50 TC 33 Z9 34 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD AUG PY 2007 VL 82A IS 2 BP 323 EP 335 DI 10.1002/jbm.a.30974 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 187GW UT WOS:000247836600008 PM 17295240 ER PT J AU Cowan, J Lozano-Calderon, S Ring, D AF Cowan, James Lozano-Calderon, Santiago Ring, David TI Quality of prospective controlled Randomized trials SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SHOCK-WAVE THERAPY; BOTULINUM TOXIN INJECTION; TENNIS ELBOW; LATERAL EPICONDYLITIS; CORTICOSTEROID INJECTION; DOUBLE-BLIND; TENDINOPATHY; SURGERY; LASER AB Background: The Oxford Levels of Evidence are now routinely assigned at many orthopaedic journals. One disadvantage of this approach is that study designs with a higher level of evidence may be given greater weight than the overall quality of the study merits. In other words, there is no guarantee that research is scientifically valid simply because a more sophisticated study design was employed. The aim of this study was to review Level-I and II therapeutic studies on lateral epicondylitis to measure variation in quality among the highest-level study designs. Methods: Fifty-four prospective randomized therapeutic trials involving patients with lateral epicondylitis were evaluated by two independent reviewers according to the Oxford Levels of Evidence, a modification of the Coleman Methodology Score (a 0 to 100-point scale), and the revised CONSORT (Consolidated Standards of Reporting Trials) score. Results: The two reviewers were consistent in their use of the Oxford Levels of Evidence (kappa = 0.73, p < 0.01), the modified Coleman Methodology Score (kappa = 0.73; p < 0.01), and the CONSORT score (kappa = 0.53; p < 0.01). Both reviewers rated the majority of studies as Level II (91% and 94%) and as unsatisfactory according to the Coleman Methodology Score (87% and 89%) and the CONSORT score (62% and 63%). Areas of deficiency included poor descriptions of recruitment (>90% of the trials), power-level calculations (73%), randomization (58%), blinding (90%), and participant flow (50%) as well as inadequate follow-up, sample size, and blinding. Conclusions: The use of the gold-standard trial design, the prospective randomized therapeutic study (Level-I or II evidence), does not ensure quality research or reporting. Critical analysis of scientific work is important regardless of the study design. Clinical scientists should be familiar with the CONSORT criteria and adhere to them when reporting clinical trials. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr 2100, Boston, MA 02114 USA. RP Cowan, J (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr 2100, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 26 TC 37 Z9 37 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 AUG PY 2007 VL 89A IS 8 BP 1693 EP 1699 DI 10.2106/JBJS.F00858 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 197HX UT WOS:000248546300004 PM 17671006 ER PT J AU Kozloff, KM Weissleder, R Mahmood, U AF Kozloff, Kenneth M. Weissleder, Ralph Mahmood, Umar TI Noninvasive optical detection of bone mineral SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone mineralization; bone turnover markers; molecular imaging; bisphosphonates ID IN-VIVO; OSTEOBLAST LINEAGE; FLUORESCENCE PROBE; CELLS; COLLAGEN; CANCER; MOUSE; RAT; PHARMACOKINETICS; BISPHOSPHONATES AB FRFP binds to mineral at osteoblastic, osteoclastic, and quiescent surfaces, with accumulation likely modulated by vascular delivery. In vivo visualization and quantification of binding can be accomplished noninvasively in animal models through optical tomographic imaging. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, CPZN 8226,185 Cambridge St, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [R24CA-02782, T32-CA079443]; NIBIB NIH HHS [R01EB001872] NR 42 TC 41 Z9 41 U1 0 U2 3 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 AUG PY 2007 VL 22 IS 8 BP 1208 EP 1216 DI 10.1359/JBMR.070504 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194ZK UT WOS:000248382100008 PM 17488196 ER PT J AU Bangs, ME Emslie, GJ Spencer, TJ Ramsey, JL Carlson, C Bartky, EJ Busner, J Duesenberg, DA Harshawat, P Kaplan, SL Quintana, H Allen, AJ Sumner, CR AF Bangs, Mark E. Emslie, Graham J. Spencer, Thomas J. Ramsey, Janet L. Carlson, Christopher Bartky, Eric J. Busner, Joan Duesenberg, David A. Harshawat, Paras Kaplan, Stuart L. Quintana, Humberto Allen, Albert J. Sumner, Calvin R. CA Atomoxetine ADHD Comorbid MDD Study Grp TI Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ONCE-DAILY ATOMOXETINE; PROSPECTIVE FOLLOW-UP; CHILDREN; PLACEBO; ADHD; PREVALENCE; SUICIDE; MANIA; RELIABILITY AB This double-blind study examined efficacy and safety of atomoxetine (ATX; <= 1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, >= 1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, >= 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent: Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD. C1 Lilly Res Labs, Indianapolis, IN USA. Texas So Univ, Sch Med, Dept Psychiat, Dallas, TX USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Morristown Mem Hosp, Morristown, NJ USA. Penn & PharmStar, Wayne, PA USA. Mercy Hlth Res, Chesterfield, MI USA. Clinco, Terre Haute, IN USA. Penn State Coll Med, Hershey, PA USA. Dev Fdn, W Chester, PA USA. Louisiana State Univ, Ctr Hlth Sci, New Orleans, LA USA. RP Bangs, ME (reprint author), Lilly Res Labs, Indianapolis, IN USA. EM bangsme@lilly.com NR 37 TC 54 Z9 57 U1 3 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2007 VL 17 IS 4 BP 407 EP 419 DI 10.1089/cap.2006.0066 PG 13 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 210SB UT WOS:000249474800002 ER PT J AU Olvera, RL Caetano, SC Fonseca, M Nicoletti, M Stanley, JA Chen, HH Hatch, JP Hunter, K Pliszka, SR Soares, JC AF Olvera, Rene L. Caetano, Sheila C. Fonseca, Manoela Nicoletti, Mark Stanley, Jeffrey A. Chen, Hua Hsuan Hatch, John P. Hunter, Kristina Pliszka, Steven R. Soares, Jair C. TI Low levels of N-acetyl aspartate in the left dorsolateral prefrontal cortex of pediatric bipolar patients SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; DEFICIT HYPERACTIVITY DISORDER; PROTON MR SPECTROSCOPY; CHILDHOOD-ONSET SCHIZOPHRENIA; WHITE-MATTER HYPERINTENSITIES; PROSPECTIVE FOLLOW-UP; IN-VIVO EVIDENCE; ATTENTION-DEFICIT; MOOD DISORDERS; NEUROPSYCHIATRIC DISORDERS AB Background: Increasing evidence suggests abnormalities in the structure, function, and neurochemistry of the frontal cortex in pediatric bipolar ( BP) patients. We conducted a single-voxel proton magnetic resonance spectroscopy (H-1 MRS) of the left dorsolateral prefrontal cortex (DLPFC) of pediatric BP patients, expecting lower N-acetyl-aspartate (NAA) levels within that brain region compared to healthy comparison subjects. Methods: We studied 35 pediatric BP (23 BP type I, 12 BP type II; mean age +/- SD = 13.2 +/- 2.9 years; 18 females) and 36 healthy controls (mean age +/- SD = 13.7 +/- 2.6 years, 17 females). A short echo time, single-voxel H-1 spectroscopy approach point-resolved spectroscopy (PRESS) sequence, measurements of metabolites was performed on a 1.5T Philips MR system. Results: BP subjects had significantly lower NAA levels in the left DLPFC compared to healthy controls (F = 4.21, df = 1, 68, p = 0.04). There was not a significant difference between groups for phosphocreatine + creatine (PCr + Cr), glycerolphosphocholine + phosphocholine (GPC + PC), myo-inositol (mI), or glutamate. Further analyses revealed a significant reduction of NAA in our early puberty group compared to controls (Mann-Whitney U-test statistic = 52.00, p = 0.014), but not for BP versus controls in other pubertal groups. Conclusions: BP subjects have lower NAA levels in the left DLPFC compared to healthy subjects, suggesting neuronal dysfunction in this region. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOODS CNS Program, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Psychiat Serv, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande do Sul, Sch Med, Dept Res Unit, Porto Alegre, RS, Brazil. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM jsoares@med.unc.edu RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [M01-RR-01346, RR 020571]; NIMH NIH HHS [K23-MH068280, MH 01736, MH 068662, MH 068766, MH69774] NR 82 TC 27 Z9 27 U1 4 U2 8 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 AUG PY 2007 VL 17 IS 4 BP 461 EP 473 DI 10.1089/cap.2007.0102 PG 13 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 210SB UT WOS:000249474800006 PM 17822341 ER PT J AU Lawson, EA Miller, KK Mathur, VA Misra, M Meenaghan, E Herzog, DB Klibanski, A AF Lawson, Elizabeth A. Miller, Karen K. Mathur, Vani A. Misra, Madhusmita Meenaghan, Erinne Herzog, David B. Klibanski, Anne TI Hormonal and nutritional effects on cardiovascular risk markers in young women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; ANOREXIA-NERVOSA; POSTMENOPAUSAL WOMEN; EATING-DISORDERS; HYPOTHALAMIC AMENORRHEA; PLUS PROGESTIN AB Context: Cardiovascular (CV) risk markers, including high-sensitivity C-reactive protein (hsCRP), are increasingly important in predicting cardiac events. A favorable CV risk profile might be expected in anorexia nervosa (AN) due to low body weight and dietary fat intake. However, women with AN have decreased IGF-I levels reflecting decreased GH action, and IGF-I deficiency is associated with elevated hsCRP. Moreover, oral estrogens, known to increase hsCRP in other populations, are commonly prescribed in AN. To date, hsCRP levels and their physiological determinants have not been reported in women with AN. Objective: We examined the relationship between CV risk markers, undernutrition, IGF-I, and oral estrogens, specifically hypothesizing that in the setting of undernutrition, AN would be associated with low hsCRP despite low IGF-I levels and that those women taking oral contraceptive pills (OCPs) would have higher hsCRP and lower IGF-I levels. Design and Setting: We conducted a cross- sectional study at a clinical research center. Study Participants: Subjects included 181 women: 140 women with AN [85 not receiving OCPs (AN- E) and 55 receiving OCPs (AN + E)] and 41 healthy controls [28 not receiving OCPs (HC- E) and 13 receiving OCPs (HC + E)]. Main Outcome Measures: We assessed hsCRP, IL- 6, IGF- I, low- density lipoprotein (LDL), and high-density lipoprotein (HDL). Results: Despite low weight, more than 20% of AN + E had high-risk hsCRP levels. AN + E had higher hsCRP than AN-E. AN-E had lower mean hsCRP levels than healthy controls (HC + E and HC-E). IL-6 levels were higher in AN + E with elevated hsCRP (> 3 mg/ liter) than in AN + E with normal hsCRP levels. IGF-I was inversely associated with hsCRP in healthy women, suggesting a protective effect of GH on CV risk. However, this was not seen in AN. Few patients in any group had high-risk LDL or HDL levels. Conclusions: Although hsCRP levels are lower in AN than healthy controls, OCP use puts such women at a greater than 20% chance of having hsCRP in the high-CV-risk (> 3 mg/ liter) category. The elevated mean IL-6 in women with AN and high-risk hsCRP levels suggests that increased systemic inflammation may underlie the hsCRP elevation in these patients. Although OCP use in AN was associated with slightly lower mean LDL and higher mean HDL, means were within the normal range, and few patients in any group had high- risk LDL or HDL levels. IGF-I levels appear to be important determinants of hsCRP in healthy young women. In contrast, IGF-I does not appear to mediate hsCRP levels in AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM AKlibanski@partners.org OI Mathur, Vani/0000-0002-9395-940X FU NCRR NIH HHS [M01 RR001066, M01 RR01066]; NIDDK NIH HHS [R01 DK052625, P30 DK040561, P30 DK040561-12, R01-DK52625] NR 62 TC 10 Z9 11 U1 1 U2 1 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 AUG PY 2007 VL 92 IS 8 BP 3089 EP 3094 DI 10.1210/jc.2007-0364 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600040 PM 17519306 ER PT J AU Kim, CJ Kaplan, LE Perwad, F Huang, NW Sharma, A Choi, Y Miller, WL Portale, AA AF Kim, Chan Jong Kaplan, Larry E. Perwad, Farzana Huang, Ningwu Sharma, Amita Choi, Yong Miller, Walter L. Portale, Anthony A. TI Vitamin D 1 alpha-hydroxylase gene mutations in patients with 1 alpha-hydroxylase deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 25-HYDROXYVITAMIN D-3 1-ALPHA-HYDROXYLASE; D-DEPENDENT RICKETS; ENZYME-ACTIVITY; CLONING; FAMILIES; DISEASE; KIDNEY; CDNA; DNA AB Context: Vitamin D 1 alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1, is an autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia and is caused by mutations of the 25-hydroxyvitamin D 1 alpha-hydroxylase (1 alpha-hydroxylase, CYP27B1) gene. The human gene encoding the 1 alpha-hydroxylase is 5 kb in length, located on chromosome 12, and comprises nine exons and eight introns. We previously isolated the human 1 alpha-hydroxylase cDNA and gene and identified 19 different mutations in 25 patients with 1 alpha-hydroxylase deficiency. Objectives, Patients, and Methods: We analyzed the 1 alpha-hydroxylase gene of 10 patients, five from Korea, two from the United States, and one each from Argentina, Denmark, and Morocco, all from nonconsanguineous families. Each had clinical and radiographic features of rickets, hypocalcemia, and low serum concentrations of 1,25-dihydroxyvitamin D(3). Results: Direct sequencing identified the responsible 1 alpha-hydroxylase gene mutations in 19 of 20 alleles. Four novel and four known mutations were identified. The new mutations included a nonsense mutation in exon 6, substitution of adenine for guanine (2561G -> A) creating a stop signal at codon 328; deletion of adenine in exon 9 (3922delA) causing a frameshift; substitution of thymine for cytosine in exon 2 (1031C -> T) causing the amino acid change P112L; and a splice site mutation, substitution of adenine for guanine in the first nucleotide of intron 7 (IVS7 + 1 G -> A) causing a frameshift. Conclusions: Mutations in the 1 alpha- hydroxylase gene previously were identified in 44 patients, to which we add 10 more. The studies show a strong correlation between 1 alpha- hydroxylase mutations and the clinical findings of 1 alpha- hydroxylase deficiency. C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Seoul Natl Univ, Childrens Hosp, Dept Pediat, Seoul 110744, South Korea. RP Portale, AA (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. EM aportale@peds.ucsf.edu RI Miller, Walter/J-3696-2012 FU NIDDK NIH HHS [DK37922] NR 24 TC 40 Z9 44 U1 0 U2 1 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 AUG PY 2007 VL 92 IS 8 BP 3177 EP 3182 DI 10.1210/jc.2006-2664 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 197QK UT WOS:000248570600054 PM 17488797 ER PT J AU Sever, S Altintas, MM Nankoe, SR Moller, CC Ko, D Wei, CL Henderson, J del Re, EC Hsing, L Erickson, A Cohen, CD Kretzier, M Kerjaschki, D Rudensky, A Nikolic, B Reiser, J AF Sever, Sanja Altintas, Mehmet M. Nankoe, Sharif R. Moller, Clemens C. Ko, David Wei, Changli Henderson, Joel del Re, Elizabetta C. Hsing, Lianne Erickson, Ann Cohen, Clemens D. Kretzier, Matthias Kerjaschki, Dontscho Rudensky, Alexander Nikolic, Boris Reiser, Jochen TI Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PUROMYCIN AMINONUCLEOSIDE NEPHROSIS; MEDIATED ENDOCYTOSIS; PROCATHEPSIN-L; EXPRESSION; GENE; ACTIVATION; PODOCYTES; VESICLE; GTPASE; MUTANT AB Kidney podocytes and their foot processes maintain the ultrafiltration barrier and prevent urinary protein loss (proteinuria). Here we show that the GTPase dynamin is essential for podocyte function. During proteinuric kidney disease, induction of cytoplasmic cathepsin L leads to cleavage of dynamin at an evolutionary conserved site, resulting in reorganization of the podocyte actin cytoskeleton and proteinuria. Dynamin mutants that lack the cathepsin L site, or render the cathepsin L site inaccessible through dynamin self-assembly, are resistant to cathepsin L cleavage. When delivered into mice, these mutants restored podocyte function and resolve proteinuria. Our study identifies dynamin as a critical regulator of renal permselectivity that is specifically targeted by proteolysis under pathological conditions. C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. MGH, Program Glomol Dis, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. Univ Munich, Med Poliklin, D-80539 Munich, Germany. Univ Michigan, Sch Med, Div Nephrol, Dept Internal Med, Ann Arbor, MI 48109 USA. Vienna Med Univ, Clin INst Pathol, Vienna, Austria. Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Sever, S (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. EM ssever@partners.org; jreiser@partners.org OI Altintas, Mehmet/0000-0002-1871-6985 FU NIDDK NIH HHS [DK38452, DK43341, DK57521, P01 DK038452, P30 DK057521, R01 DK064787, R01 DK073495, R01 DK64787, T32 DK007540, T32DK007540] NR 39 TC 111 Z9 117 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2007 VL 117 IS 8 BP 2095 EP 2104 DI 10.1172/JCI32022 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196JS UT WOS:000248478100017 PM 17671649 ER PT J AU Farese, RV Sajan, MP Yang, H Li, PF Mastorides, S Gower, WR Nimal, S Choi, CS Kim, S Shulman, GI Kahn, CR Braun, U Leitges, M AF Farese, Robert V. Sajan, Mini P. Yang, Hong Li, Pengfei Mastorides, Steven Gower, William R., Jr. Nimal, Sonali Choi, Cheol Soo Kim, Sheene Shulman, Gerald I. Kahn, C. Ronald Braun, Ursula Leitges, Michael TI Muscle-specific knockout of PKC-lambda impairs qlucose transport and induces metabolic and diabetic syndromes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-KINASE-C; STIMULATED GLUCOSE-TRANSPORT; HUMAN SKELETAL-MUSCLE; INSULIN-RESISTANCE; 3T3-L1 ADIPOCYTES; POTENTIAL ROLE; GLUCOSE-TRANSPORTER-4 TRANSLOCATION; PHOSPHATIDYLINOSITOL 3-KINASE; GLUT4 TRANSLOCATION; NIDDM SUBJECTS AB Obesity, the metabolic syndrome, and type 2 diabetes mellitus (T2DM) are major global health problems. Insulin resistance is frequently present in these disorders, but the causes and effects of such resistance are unknown. Here, we generated mice with muscle-specific knockout of the major murine atypical PKC (aPKC), PKC-lambda, a postulated mediator for insulin-stimulated glucose transport. Glucose transport and translocation of glucose transporter 4 (GLUT4) to the plasma membrane were diminished in muscles of both homozygous and heterozygous PKC-lambda knockout mice and were accompanied by systemic insulin resistance; impaired glucose tolerance or diabetes; islet beta cell hyperplasia; abdominal adiposity; hepatosteatosis; elevated serum triglycerides, FFAs, and LDL-cholesterol; and diminished HDL-cholesterol. in contrast to the defective activation of muscle aPKC, insulin signaling and actions were intact in muscle, liver, and adipocytes. These findings demonstrate the importance of aPKC in insulin-stimulated glucose transport in muscles of intact mice and show that insulin resistance and resultant hyperinsulinemia owing to a specific defect in muscle aPKC is sufficient to induce abdominal obesity and other lipid abnormalities of the metabolic syndrome and T2DM. These findings are particularly relevant because humans who have obesity, impaired glucose tolerance, and T2DM reportedly have defective activation and/or diminished levels of muscle aPKC. C1 James A Haley Vet Hosp, Tampa, FL 33612 USA. Roskamp Inst, Sarasota, FL USA. Univ S Florida, Coll Med, Dept Mol Med, Tampa, FL USA. Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Joslin Res Fdn, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hannover Med Sch, Dept Med, Div Nephrol, D-3000 Hannover, Germany. Biotechnol Ctr Oslo, Oslo, Norway. RP Farese, RV (reprint author), James A Haley Vet Hosp, 13000 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM rfarese@health.usf.edu RI Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [R01 DK065969, R01 DK040936, DK30136, DK38079, U24 DK059635] NR 47 TC 105 Z9 109 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2007 VL 117 IS 8 BP 2289 EP 2301 DI 10.1172/JCI31408 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196JS UT WOS:000248478100037 PM 17641777 ER PT J AU Lee, HJ Selesniemi, K Niikura, Y Niikura, T Klein, R Dombkowski, DM Tilly, JL AF Lee, Ho-Joon Selesniemi, Kaisa Niikura, Yuichi Niikura, Teruko Klein, Rachael Dombkowski, David M. Tilly, Jonathan L. TI Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; HEMATOLOGICAL MALIGNANCIES; PERIPHERAL-BLOOD; EGGS FOREVER; IN-VITRO; DERIVATION; MICE; CANCER; PREGNANCIES AB Purpose Although early menopause frequently occurs in female cancer patients after chemotherapy ( CTx), bone marrow ( BM) transplantation ( BMT) has been linked to an unexplained return of ovarian function and fertility in some survivors. Studies modeling this in mice have shown that BMT generates donor-derived oocytes in CTx-treated recipients. However, a subsequent report claimed that ovulated eggs are not derived from BM and that BM-derived oocytes reported previously are misidentified immune cells. This study was conducted to further clarify the impact of BMT on female reproductive function after CTx using a preclinical mouse model. Methods Female mice were administered CTx followed by BMT using coat color-mismatched female donors. After housing with males, the number of pregnancies and offspring genotype were recorded. For cell tracking, BM from germline-specific green fluorescent protein-transgenic mice was transplanted into CTx-treated wild-type recipients. Immune cells were sorted from blood and analyzed for germline markers. Results BMT rescued long-term fertility in CTx-treated females, but all offspring were derived from the recipient germline. Cell tracking showed that donor-derived oocytes were generated in ovaries of recipients after BMT, and two lines of evidence dispelled the claim that these oocytes are misidentified immune cells. Conclusion These data from a preclinical mouse model validate a testable clinical strategy for preserving or resurrecting ovarian function and fertility in female cancer patients after CTx, thus aligning with recommendations of the 2005 National Cancer Institute Breast Cancer Progress Review Group and President's Cancer Panel to prioritize research efforts aimed at improving the quality of life in cancer survivors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regnerat Med, Boston, MA USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, THR-901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU NIA NIH HHS [R37-AG012279] NR 49 TC 116 Z9 123 U1 2 U2 13 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 AUG 1 PY 2007 VL 25 IS 22 BP 3198 EP 3204 DI 10.1200/JCO.2006.10.3028 PG 7 WC Oncology SC Oncology GA 200DL UT WOS:000248744000005 PM 17664466 ER PT J AU Yen, TWF Kuerer, HM Ottesen, RA Rouse, L Niland, JC Edge, SB Theriault, RL Weeks, JC AF Yen, Tina W. F. Kuerer, Henry M. Ottesen, Rebecca A. Rouse, Layla Niland, Joyce C. Edge, Stephen B. Theriault, Richard L. Weeks, Jane C. TI Impact of randomized clinical trial results in the National Comprehensive Cancer Network on the use of tamoxifen after breast surgery for ductal carcinoma in situ SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, Hlth Sci Ctr ID SURGICAL ADJUVANT BREAST; AROMATASE INHIBITORS; COMBINATION TRIAL; PREVENTION TRIALS; ATAC ARIMIDEX; UPDATE; WOMEN AB Purpose The National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery ( BCS) and radiotherapy for ductal carcinoma in situ ( DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network ( NCCN) centers. Patients and Methods Tamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses. Results Overall, 41% of patients ( 665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 ( odds ratio [ OR], 3.85; P < .0001), BCS in patients younger than 70 years ( OR, 3.21; P < .0073), no history of cerebrovascular or peripheral vascular disease ( OR, 3.13; P = .0071), receipt of radiotherapy ( OR, 1.82; P = .0009), and previous hysterectomy ( OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy ( P < .0001). Conclusion Tamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population. C1 Med Coll Wisconsin, Div Gen Surg, Milwaukee, WI 53226 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol & Med Oncol, Houston, TX 77030 USA. City Hope Natl Med Ctr, Dept Informat Sci, Duarte, CA 91010 USA. Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Yen, TWF (reprint author), Med Coll Wisconsin, Div Gen Surg, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM tyen@mcw.edu NR 20 TC 25 Z9 26 U1 1 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 AUG 1 PY 2007 VL 25 IS 22 BP 3251 EP 3258 DI 10.1200/JCO.2006.10.2699 PG 8 WC Oncology SC Oncology GA 200DL UT WOS:000248744000013 PM 17577019 ER PT J AU Kreicbergs, UC Lannen, P Onelov, E Wolfe, J AF Kreicbergs, Ulrika C. Lannen, Patrizia Onelov, Erik Wolfe, Joanne TI Parental grief after losing a child to cancer: Impact of professional and social support on long-term outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FOLLOW-UP; BEREAVEMENT; CARE; NATIONWIDE; SYMPTOMS; DISTRESS; DEATH; WORK; HELP AB Purpose It is still uncertain whether or not parents can ever come to terms with the loss of a child and whether professional or social support facilitate the long-term grief process. Methods A Swedish population-based study, which sent an anonymous, mail-in questionnaire to parents who had lost a child to a malignancy 4 to 9 years earlier, gained the participation of 449 ( 80%) of 561 parents. Parents were asked whether, and to what extent, they had worked through their grief. Questions were also asked regarding those who provided parents with support. We examined candidate factors to determine their associations with greater likelihood of working through parental grief. Results Overall, most parents ( 74%) stated that they had worked through their grief "a lot" or "completely" at the time of the follow-up. Parents who had shared their problems with others during the child's illness ( fathers: relative risk [ RR], 3.0; 95% Cl, 1.8 to 5.0; mothers: RR 1.9; 95% Cl, 1.2 to 2.8) and who had access to psychological support during the last month of their child's life ( fathers: RR 1.4; 95% Cl, 1.0 to 1.8; mothers: RR 1.3; 95% Cl, 1.1 to 1.6) were more likely to have worked through their grief. In cases where health care staff offered parents counseling during the child's last month, the parents were more likely to have worked through their grief ( fathers: RR 1.5; 95% Cl, 1.2 to 1.8; mothers; RR 1.2; 95% Cl, 1.1 to 1.4). Conclusion Most parents eventually work through the grief associated with losing a child to cancer. In the long term, sharing the emotional burden with others facilitates the grieving process. C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr, Dept Peadiat Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Karolinska Inst, Dept Women & Childs Hlth, Div Clin Canc Epidemiol, Stockholm, Sweden. Univ Bern, Dept Psychol, Bern, Switzerland. RP Kreicbergs, UC (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr, Dept Peadiat Oncol, Ctr Outcomes & Policy Res, 44 Binney St,CP 306, Boston, MA 02115 USA. EM ulrika_kreicbergs@dfci.harvard.edu FU NCI NIH HHS [5 K07 CA 096746] NR 32 TC 61 Z9 61 U1 2 U2 17 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 AUG 1 PY 2007 VL 25 IS 22 BP 3307 EP 3312 DI 10.1200/JCO.2006.10.0743 PG 6 WC Oncology SC Oncology GA 200DL UT WOS:000248744000021 PM 17664479 ER PT J AU Sands, BE Kaplan, GG AF Sands, Bruce E. Kaplan, Gilaad G. TI The role of TNF alpha in ulcerative colitis SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review DE inflammatory bowel disease; infliximab; therapy ID INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; ACTIVE CROHNS-DISEASE; POUCH-ANAL ANASTOMOSIS; PLACEBO-CONTROLLED TRIAL; MONOCLONAL-ANTIBODY; INDETERMINATE COLITIS; MAINTENANCE THERAPY; CERTOLIZUMAB PEGOL; BIOLOGIC THERAPY AB Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerative colitis have highlighted the importance of cytokines such as tumor necrosis factor alpha (TNF alpha) in the inflammatory process. TNFa is a proinflammatory mediator that plays an integral role in the pathogenesis of inflammatory bowel disease. In addition, mounting evidence indicates a genetic association between TNFa and ulcerative colitis. Furthermore, increased TNFa levels have been demonstrated in studies of patients with ulcerative colitis. TNFa is likely an important component in the pathophysiology of ulcerative colitis, and thus agents targeting TNFa in ulcerative colitis have been studied. Recent randomized controlled trials have confirmed that biologic anti-TNF alpha therapy is effective in ulcerative colitis. Soluble TNFa receptors or biologic agents that suppress or inhibit TNFa production may also show therapeutic promise. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. Ctr Study Inflammat Bowel Dis, Gastrointestinal Unit, Boston, MA USA. RP Sands, BE (reprint author), MGH Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 99 TC 42 Z9 43 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 2007 VL 47 IS 8 BP 930 EP 941 DI 10.1177/0091270007301623 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 195MT UT WOS:000248417000001 PM 17567930 ER PT J AU Pearson, KH Nonacs, RM Vigueya, AC Heller, VL Petrillo, LF Brandes, M Hennen, J Cohen, LS AF Pearson, Kimberly H. Nonacs, Ruta M. Vigueya, Adele C. Heller, Vicki L. Petrillo, Laura F. Brandes, Mina Hennen, John Cohen, Lee S. TI Birth outcomes following prenatal exposure to antidepressants SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 154th Annual Meeting of the American-Psychiatric-Association CY MAY 05-10, 2001 CL NEW ORLEANS, LA SP Amer Psychiat Assoc ID SEROTONIN-REUPTAKE INHIBITORS; MATERNAL DEPRESSIVE SYMPTOMS; BIPOLAR DISORDER; PREGNANCY; FLUOXETINE; WOMEN; RISK; NEWBORN; PREVALENCE; RECURRENCE AB Background: Antidepressant use during pregnancy and the peripartum period is common despite the absence of clear evidence-based guidelines to direct clinical use of these compounds. Method: We compared obstetrical and neonatal outcomes as recorded in medical records among m 84 pregnant women with major depressive or anxiety disorders (DSM-IV criteria) who took antidepressants during pregnancy (cases) versus a 2:1 age- and parity-matched control group of 168 unexposed women. Women in the case group had sought psychiatric consultation regarding the use Of medication from the Perinatal and Reproductive Psychiatry Program at the Massachusetts General Hospital between 1996 and 2000. Results: There were no significant differences among cases versus controls and their offspring, with respect to various neonatal and obstetrical outcomes, including gestational age and weight, although 1-minute Apgar scores were slightly lower in exposed infants. Admissions to the special care nursery were more frequent, but briefer and based on relatively minor indications, among case newborns. There were no significant differences in neonatal outcomes between exposures to serotonin reuptake inhibitor (SRI) and tricyclic (TCA) antidepressants. Conclusion: This retrospective cohort study found no evidence of major increases in risk of adverse obstetrical or neonatal outcomes following prenatal exposure to antidepressants, nor between SRIs and TCAs. Larger, prospective studies with specific neurobehavioral measures are required to resolve current uncertainties about safe and effective use of antidepressants by pregnant women. C1 Massachusetts Gen Hosp, Perinatal & Reproduct Psychiat Program, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Ginecol, Boston, MA 02115 USA. Johns Hopkins Univ Hosp, Dept Psychiat, Baltimore, MD 21287 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Pearson, KH (reprint author), Massachusetts Gen Hosp, Perinatal & Reproduct Psychiat Program, 185 CVambridge St 2nd Floor, Boston, MA 02114 USA. EM khpearson@partners.org NR 33 TC 26 Z9 26 U1 3 U2 7 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 AUG PY 2007 VL 68 IS 8 BP 1284 EP 1289 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 207PB UT WOS:000249261900017 PM 17854255 ER PT J AU Evins, AE Cather, C Culhane, MA Birnbaum, A Horowitz, J Hsieh, E Freudenreich, O Henderson, DC Schoenfeld, DA Rigotti, NA Goff, DC AF Evins, A. Eden Cather, Corinne Culhane, Melissa A. Birnbaum, Alan Horowitz, Jonathan Hsieh, Elaine Freudenreich, Oliver Henderson, David C. Schoenfeld, David A. Rigotti, Nancy A. Goff, Donald C. TI A 12-week double-blind, placebo-controlled study of bupropion SR added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Conference of the Society-for-Research-on-Nicotine-and-Tobacco CY FEB 18, 2006 CL Orlando, FL SP Soc Res Nicotine & Tobacco ID SUSTAINED-RELEASE BUPROPION; PURSUIT EYE-MOVEMENTS; CONTROLLED-TRIAL; CIGARETTE-SMOKING; NASAL SPRAY; FOLLOW-UP; DEPENDENCE; DEFICITS; SMOKERS; PATCH AB The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention. C1 Massachusetts Gen Hosp, Addict Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Treatment & Res Ctr, Boston, MA 02114 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Addict Res Program, 25 Stanford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [K23 DA00510]; PHS HHS [05B1MACMHS-04] NR 48 TC 83 Z9 85 U1 3 U2 14 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 AUG PY 2007 VL 27 IS 4 BP 380 EP 386 DI 10.1097/JCP.0b013e3180ca86fa PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 190MG UT WOS:000248062400010 PM 17632223 ER PT J AU Biederman, J Ball, SW Monuteaux, MC Surman, CB Johnson, JL Zeitlin, S AF Biederman, Joseph Ball, Sarah W. Monuteaux, Michael C. Surman, Craig B. Johnson, Jessica L. Zeitlin, Sarah TI Are girls with ADHD at risk for eating disorders? Results from a controlled, five-year prospective study SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE attention-deficit/hyperactivity disorder; eating disorders; longitudinal ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; B PERSONALITY-DISORDER; BULIMIA-NERVOSA; GROWTH DEFICITS; METHYLPHENIDATE TREATMENT; PSYCHIATRIC COMORBIDITY; NUTRITIONAL-STATUS; ANXIETY DISORDERS; RENAL DISEASES; CHILDREN AB Objective: To evaluate the association between attention-deficit/hyperactivity disorder (ADHD) and eating disorders in a large adolescent population of girls with and without ADHD. Method: We estimated the incidence of lifetime eating disorders (either anorexia or bulimia nervosa) using Cox proportional hazard survival models. Comparisons between ADHD girls with and without eating disorders were then made on measures of comorbidity, course of ADHD, and growth and puberty. Results: ADHD girls were 3.6 times more likely to meet criteria for an eating disorder throughout the follow-up period compared to control females. Girls with eating disorders had significantly higher rates of major depression, anxiety disorders, and disruptive behavior disorder compared to ADHD girls without eating disorders. Girls with ADHD and eating disorders had a significantly earlier mean age at menarche than other ADHD girls. No other differences in correlates of ADHD were detected between ADHD girls with and without eating disorders. Conclusions: ADHD significantly increases the risk of eating disorders. The presence of an eating disorder in girls with ADHD heightens the risk of additional morbidity and dysfunction. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org FU NICHD NIH HHS [5 R01 HD36317-07] NR 37 TC 58 Z9 59 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD AUG PY 2007 VL 28 IS 4 BP 302 EP 307 DI 10.1097/DBP.0b013e3180327917 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 202RL UT WOS:000248920700007 PM 17700082 ER PT J AU Baugh, CWA Thomas, SH Nadel, ES Brown, DFM Binder, W White, B Bisanzo, M Peak, D AF Baugh, Christopher W. A. Thomas, Stephen H. Nadel, Eric S. Brown, David F. M. Binder, William White, Benjamin Bisanzo, Mark Peak, David TI Complicated soft tissue infection SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID RESISTANT STAPHYLOCOCCUS-AUREUS; PREVALENCE; ABSCESS; SKIN C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Bulfinch 105, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2007 VL 33 IS 2 BP 181 EP 185 DI 10.1016/j.jemermed.2007.05.028 PG 5 WC Emergency Medicine SC Emergency Medicine GA 202HJ UT WOS:000248892300015 PM 17692771 ER PT J AU Bell, ME Goodman, LA Dutton, MA AF Bell, Margret E. Goodman, Lisa A. Dutton, Mary Ann TI The dynamics of staying and leaving: Implications for battered women's emotional well-being and experiences of violence at the end of a year SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE longitudinal; intimate partner violence; relationship status; leaving; staying ID INTIMATE PARTNER VIOLENCE; ABUSIVE RELATIONSHIP; RISK; TIME; STRATEGIES; SEPARATION; RESPONSES; CONFLICT; DECISION; DEPRESSION AB Much of the discourse on intimate partner violence assumes that women must end their relationship with their abusive partner to increase their safety and emotional well-being. Few studies, however, exist to support this assumption. Equally problematic, those studies that do exist have failed to distinguish women who leave and stay out from those who leave only to later return. Comparing emotional well-being and experiences of violence for 206 low-income, primarily Black battered women following different relationship trajectories, this longitudinal study found that women both separated from and together with their partner for the entire year of the study fared best at the end of that year compared to women "in" and "out" of the relationship over time. Beyond challenging common assumptions, these findings highlight the importance of considering the larger context within which an individual instance of leaving occurs. C1 Dept Vet Affairs Off Mental Hlth Serv, Mil Sexual Trauma Support Team, Jamaica Plain, MA 02130 USA. Natl Ctr PTSD, VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. Boston Coll, Lynch Sch Educ, Dept Counselling Dev & Educ Psychol, Chestnut Hill, MA 02467 USA. Georgetown Univ, Dept Psychiat, Washington, DC 20007 USA. RP Bell, ME (reprint author), Dept Vet Affairs Off Mental Hlth Serv, Mil Sexual Trauma Support Team, 150 S Hunington Ave,116B-3, Jamaica Plain, MA 02130 USA. EM mebell@aya.yale.edu; goodmalc@bc.edu; mad27@georgetown.edu NR 87 TC 30 Z9 30 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD AUG PY 2007 VL 22 IS 6 BP 413 EP 428 DI 10.1007/s10896-007-9096-9 PG 16 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 189DT UT WOS:000247970300008 ER PT J AU Cattaneo, LB Bell, ME Goodman, LA Dutton, MA AF Cattaneo, Lauren Bennett Bell, Margret E. Goodman, Lisa A. Dutton, Mary Ann TI Intimate partner violence victims' accuracy in assessing their risk of re-abuse SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE intimate partner violence; re-abuse; danger assessment; risk perception; victim accuracy; optimistic bias ID POSTTRAUMATIC-STRESS-DISORDER; BATTERED WOMEN; STRATEGIES; ASSAULT AB Using four categories of accuracy (true positive, false positive, true negative, false negative), this study explored (1) how accurately intimate partner violence (IPV) victims are able to assess their risk of re-abuse; and (2) potential predictors of accuracy. Women seeking help for IPV (N=246) rated the likelihood that they would experience physical re-abuse in the coming year and then reported 18 months later whether those risks had been realized. Victim assessments were more likely to be right than wrong, and were subject to neither a pessimistic nor optimistic bias. In the multivariate analysis, significant/marginally significant predictors of the accuracy categories were the history of violence from this and former partners, level of substance use, PTSD symptoms, and the recency of the violence. Among the more robust findings were the connection between level of stalking and true positives, and between substance use and false negatives. This study suggests that victim assessments have significant potential to inform practice, and deserve further exploration. C1 George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. Dept Vet Affairs Off Mental Hlth Serv, Mil Sexual Trauma Support Team, Jamaica Plain, MA 02130 USA. Natl Ctr PTSD, VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. Boston Coll, Lynch Sch Educ, Dept Counselling Dev & Educ Psychol, Chestnut Hill, MA 02167 USA. Georgetown Univ, Dept Psychiat, Washington, DC USA. RP Cattaneo, LB (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr,MSN 3F5, Fairfax, VA 22030 USA. EM lcattane@gmu.edu NR 45 TC 41 Z9 41 U1 2 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD AUG PY 2007 VL 22 IS 6 BP 429 EP 440 DI 10.1007/s10896-007-9097-8 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 189DT UT WOS:000247970300009 ER PT J AU Stewart, L Griffiss, JM Jarvis, GA Way, LW AF Stewart, Lygia Griffiss, J. McLeod Jarvis, Gary A. Way, Lawrence W. TI Gallstones containing bacteria are biofilms: Bacterial slime production and ability to form pigment solids determines infection severity and bacteremia SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Society-for-Surgery-of the Alimentary-Tract CY MAY 20-24, 2006 CL Los Angeles, CA SP Soc Surg Alimentary Tract DE gallstone; bacteremia; beta-glucuronidase; phospholipase; biofilm; slime; glycocalyx ID NECROSIS-FACTOR-ALPHA; BETA-GLUCURONIDASE; CHOLANGIOVENOUS REFLUX; ELECTRON-MICROSCOPY; CYSTIC-FIBROSIS; PATHOGENESIS; BILE; DISEASE; STONES; GLYCOCALYX AB Gallstone bacteria provide a reservoir for biliary infections. Slime production facilitates adherence, whereas beta-glucuronidase and phospholipase generate colonization surface. These factors facilitate gallstone formation, but their influence on infection severity is unknown. Two hundred ninety-two patients were studied. Gallstones, bile, and blood (as applicable) were cultured. Bacteria were tested for beta-glucuronidase/phospholipase production and quantitative slime production. Infection severity was correlated with bacterial factors. Bacteria were present in 43% of cases, 13% with bacteremia. Severe infections correlated directly with beta-glucuronidase/phospholipase (55% with vs 13% without, P < 0.0001), but inversely with slime production (55 vs 8%, slime < 75 or > 75, P=0.008). Low slime production and beta-glucuronidase/phospholipase production were additive: Severe infections were present in 76% with both, but 10% with either or none (P < 0.0001). beta-Glucuronidase/phospholipase production facilitated bactibilia (86% with vs 62% without, P=0.03). Slime production was 19 (+/- 8) vs 50 (+/- 10) for bacteria that did or did not cause bacteremia (P=0.004). No bacteria with slime > 75 demonstrated bacteremia. Bacteria-laden gallstones are biofilms whose characteristics influence illness severity. Factors creating colonization surface (beta-glucuronidase/phospholipase) facilitated bacteremia and severe infections; but abundant slime production, while facilitating colonization, inhibited detachment and cholangiovenous reflux. This shows how properties of the gallstone biofilm determine the severity of the associated illness. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Surg Serv, San Francisco, CA USA. San Francisco VA Med Ctr, Ctr Immunochem, San Francisco, CA USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Dept Surg, 4150 Clement St, San Francisco, CA 94121 USA. EM lygia.stewart@med.va.gov NR 38 TC 14 Z9 14 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD AUG PY 2007 VL 11 IS 8 BP 977 EP 983 DI 10.1007/s11605-007-0168-1 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 189DU UT WOS:000247970400007 PM 17546479 ER PT J AU Greer, JA Park, ER Green, AR Betancourt, JR Weissman, JS AF Greer, Joseph A. Park, Elyse R. Green, Alexander R. Betancourt, Joseph R. Weissman, Joel S. TI Primary care resident perceived preparedness to deliver cross-cultural care: An examination of training and specialty differences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; medical education; cross-cultural care ID INTERNAL-MEDICINE RESIDENTS; EFFECTIVE PEDIATRIC CARE; HEALTH-CARE; FAMILY MEDICINE; COMPETENCE; EDUCATION; PHYSICIANS; SKILLS; COMMUNICATION; PERCEPTIONS AB Objective: Previous research has shown that resident physicians report differences in training across primary care specialties, although limited data exist on education in delivering cross-cultural care. The goals of this study were to identify factors that relate to primary care residents' perceived preparedness to provide cross-cultural care and to explore the extent to which these perceptions vary across primary care specialties. Design: Cross-sectional, national mail survey of resident physicians in their last year of training. Participants: Eleven hundred fifty primary care residents specializing in family medicine (27%), internal medicine (23%), pediatrics (26%), and obstetrics/gynecology (OB/GYN) (24%). Results: Male residents as well as those who reported having graduated from U.S. medical schools, access to role models, and a greater cross-cultural case mix during residency felt more prepared to deliver cross-cultural care. Adjusting for these demographic and clinical factors, family practice residents were significantly more likely to feel prepared to deliver cross-cultural care compared to internal medicine, pediatric, and OB/GYN residents. Yet, when the quantity of instruction residents reported receiving to deliver cross-cultural care was added as a predictor, specialty differences became nonsignificant, suggesting that training opportunities better account for the variability in perceived preparedness than specialty. Conclusions: Across primary care specialties, residents reported different perceptions of preparedness to deliver cross-cultural care. However, this variation was more strongly related to training factors, such as the amount of instruction physicians received to deliver such care, rather than specialty affiliation. These findings underscore the importance of formal education to enhance residents' preparedness to provide cross-cultural care. C1 Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Greer, JA (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM jgreer2@partners.org NR 43 TC 20 Z9 20 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2007 VL 22 IS 8 BP 1107 EP 1113 DI 10.1007/s11606-007-0229-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 189SF UT WOS:000248008100007 PM 17516107 ER PT J AU Lamont, EB Dias, LE Lauderdale, DS AF Lamont, Elizabeth B. Dias, Lauren E. Lauderdale, Diane S. TI NSAIDs and colorectal cancer risk: Do administrative data support a chemopreventive effect? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer; prevention; aging ID FAMILIAL ADENOMATOUS POLYPOSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; ASPIRIN USE; MEDICARE DATA; COLON-CANCER; OSTEOARTHRITIS; POPULATION; SULINDAC; HEALTH AB Background: Randomized trials show non-steroidal anti-inflammatory drugs (NSAIDs) reduce precancerous polyps. Observational studies of the NSAID aspirin (ASA) suggest that it reduces invasive colorectal cancer (CRC) incidence, but because ASA use may also be a marker for healthy behaviors, these studies may be subject to selection bias. We sought to estimate the effectiveness of NSAIDs in CRC prevention in the population of elderly Medicare beneficiaries, minimizing this selection bias. Methods: With National Ambulatory Medical Care Survey data, we find that patients with a diagnosis of osteoarthritis (OA) are 4.4 times more likely to concurrently have NSAID use documented than patients without such a diagnosis. We use this figure to estimate the expected NSAID-mediated reduction in CRC risk associated with a diagnosis of OA. Using Survival Epidemiology and End-Results (SEER)-Medicare data, we compare cases of elderly Medicare beneficiaries diagnosed with CRC in 1995 to persons without CRC to determine if their odds of antecedent OA differ. Results: We estimate the expected NSAID-mediated reduction in CRC associated with an OA diagnosis to be between 6 and 16% (i.e., RR, 0.84-0.94). In the SEER-Medicare data, we find that individuals with a diagnosis of OA in Medicare claims in the previous 3 years had 15% lower odds of being diagnosed with CRC than individuals whose claims did not reflect antecedent OA (OR 0.85, 95%CI 0.80-0.91). Conclusions: This case-control study finds that elderly Medicare beneficiaries with histories of OA have 15% lower odds of developing CRC. These results are consistent with a preventive role for NSAIDs in CRC among the elderly. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. N Shore Med Ctr, Peabody, MA USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Med, 180A Longwood Ave, Boston, MA 02115 USA. EM lamont@hcp.med.harvard.edu FU NCI NIH HHS [K07 CA093892, K07 CA93892] NR 41 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2007 VL 22 IS 8 BP 1166 EP 1171 DI 10.1007/s11606-007-0256-7 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 189SF UT WOS:000248008100017 PM 17577606 ER PT J AU Gordon, AJ Sullivan, LE Alford, DP Arnsten, JH Gourevitch, MN Kertesz, SG Kunins, HV Merrill, JO Samet, JH Fiellin, DA AF Gordon, Adam J. Sullivan, Lynn E. Alford, Daniel P. Arnsten, Julia H. Gourevitch, Marc N. Kertesz, Stefan G. Kunins, Hillary V. Merrill, Joseph O. Samet, Jeffrey H. Fiellin, David A. TI Update in addiction medicine for the generalist SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary health care; substance-related disorders; review literature ID RANDOMIZED CONTROLLED-TRIAL; SUSTAINED-RELEASE BUPROPION; RECEPTOR PARTIAL AGONIST; UNITED-STATES; ALCOHOL DEPENDENCE; SMOKING-CESSATION; SCREENING QUESTION; PROBLEM DRINKING; PRIMARY-CARE; INTERVENTIONS C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Yale Univ, Sch Med, New Haven, CT USA. Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect,CARE Unit, Boston, MA USA. Albert Einstein Coll Med, New York, NY USA. Montefiore Med Ctr, New York, NY USA. NYU, Sch Med, New York, NY 10003 USA. Univ Alabama, Sch Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Univ Washington, Sch Med, Seattle, WA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Mailcode 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov OI Samet, Jeffrey/0000-0002-0897-3400; Fiellin, David/0000-0002-4006-010X; Gourevitch, Marc/0000-0001-6865-2126 NR 39 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2007 VL 22 IS 8 BP 1190 EP 1194 DI 10.1007/s11606-007-0133-4 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 189SF UT WOS:000248008100022 PM 17492327 ER PT J AU Werner, RM Greenfield, S Fung, C Turner, BJ AF Werner, Rachel M. Greenfield, Sheldon Fung, Constance Turner, Barbara J. TI Measuring quality of care in patients with multiple clinical conditions: Summary of a conference conducted by the society of general internal medicine SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE performance measurement; quality measures; clinically complex patients ID PAY-FOR-PERFORMANCE; COMPETING DEMANDS; DISEASE; DELIVERY; COMORBIDITY; DEPRESSION; GUIDELINES; MANAGEMENT; PROFILES; SYSTEM AB Performance measurement has been widely advocated as a means to improve health care delivery and, ultimately, clinical outcomes. However, the evidence supporting the value of using the same quality measures designed for patients with a single clinical condition in patients with multiple conditions is weak. If clinically complex patients, defined here as patients with multiple clinical conditions, present greater challenges to achieving quality goals, providers may shun them or ignore important, but unmeasured, clinical issues. This paper summarizes the proceedings of a conference addressing the challenge of measuring quality of care in the patient with multiple clinical conditions with the goal of informing the implementation of quality measurement systems and future research programs on this topic. The conference had three main areas of discussion. First, the potential problems caused by applying current quality standards to patients with multiple conditions were examined. Second, the advantages and disadvantages of three strategies to improve quality measurement in clinically complex patients were evaluated: excluding certain clinically complex patients from a given standard, relaxing the performance target, and assigning a greater weight to some measures based on the expected clinical benefit or difficulty of reaching the performance target. Third, the strengths and weaknesses of potential novel measures such change in functional status were considered. The group concurred that, because clinically complex patients present a threat to the implementation of quality measures, high priority must be assigned to a research agenda on this topic. This research should evaluate the impact of quality measurement on these patients and expand the range of quality measures relevant to the care of clinically complex patients. C1 Philadelphia VAMC, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Univ Calif Irvine, Ctr Hlth Policy Res, Irvine, CA 92717 USA. VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Werner, RM (reprint author), 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu NR 35 TC 42 Z9 42 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2007 VL 22 IS 8 BP 1206 EP 1211 DI 10.1007/s11606-007-0230-4 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 189SF UT WOS:000248008100024 PM 17516106 ER PT J AU Ruelaz, AR Diefenbach, P Simon, B Lanto, A Arterburn, D Shekelle, PG AF Ruelaz, Alicia R. Diefenbach, Pamela Simon, Barbara Lanto, Andy Arterburn, David Shekelle, Paul G. TI Perceived barriers to weight management in primary care - Perspectives of patients and providers (vol 22, pg 518, 2007) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Correction C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. VA Hlth Serv Res & Dev Ctr ESPB, Los Angeles, CA USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. RP Ruelaz, AR (reprint author), Cedars Sinai Med Ctr, MD-8700 Beverly Blvd,8th Floor,Romm 8631, Los Angeles, CA 90048 USA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2007 VL 22 IS 8 BP 1223 EP 1223 DI 10.1007/s11606-007-0236-y PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 189SF UT WOS:000248008100030 ER PT J AU Muller, T Koppikar, S Taylor, RM Carragher, F Schlenck, B Heinz-Erian, P Kronenberg, F Ferenci, P Tanner, S Siebert, U Staudingerlo, R Mieli-Vergani, G Dhawan, A AF Mueller, Thomas Koppikar, Smita Taylor, Rachel M. Carragher, Fiona Schlenck, Barbara Heinz-Erian, Peter Kronenberg, Florian Ferenci, Peter Tanner, Stuart Siebert, Uwe Staudingerlo, Roland Mieli-Vergani, Giorgina Dhawan, Anil TI Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson's disease in children SO JOURNAL OF HEPATOLOGY LA English DT Article DE Wilson's disease; copper; liver; penicillamine ID URINARY COPPER EXCRETION; LIVER-DISEASE; GENE; MUTATIONS AB Backgrounds/Aims: A urinary copper (Cu) >25 mu mol/24 h following penicillamine had a reported specificity of 98.2% and sensitivity of 88.2% in diagnosing Wilson's disease (WD). We have re-evaluated this test. Ninety-eight subjects were studied at presentation. Methods: Thirty-eight (19 girls, 19 boys; median age 10.3 years; range 5-16 years) had an ultimate diagnosis of WD. Sixty (24 girls, 36 boys; median age 10.1, range 2.3-15 years) had other fiver disorders. Urinary Cu was estimated for 24 h before (basal Cu) and for 24 h whilst giving penicillamine 500 mg orally 12 hourly x2 (post-penicillamine Cu). Results: Both basal Cu and post-penicillamine Cu differed significantly between WD patients and controls (basal Cu: median 6.5 mu mol/24 h, range 0.9-109 mu mol/24 h, versus median: 0.8 mu mol/24 h, range 0.1-19.5, p < 0.0001; post-penicillamine Cu: median 36.9 mu mol/24 h, range 1.98-219 mu mol/24 h, versus median 12.35 mu mol/24 h, range 0.5-49.8 mu mol/24 h, p < 0.0001). A post-penicillamine Cu >25 mu mol/24 h was observed in 29/38 patients with WD and in 4/60 controls. 25/ 38 WD patients were symptomatic. Twenty-three of these and 6/13 asymptomatic siblings had a positive test. The test had a sensitivity of 76% (95% confidence interval 101, 59.8-88.6%) and a specificity of 93% (95% CI, 83.8-98.2%). Sensitivity was better in symptomatic patients (92%, [95% CI; 74-99%]) than asymptomatic (46%,195% CI; 19.2-74.9%]). Conclusions: This test is valuable in the diagnosis of WD with active liver disease, but is unreliable to exclude the diagnosis in asymptomatic siblings. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Kings Coll Hosp London, Paediat Liver Ctr, London SE5 8RX, England. Med Univ Innsbruck, Dept Pediat 2, Innsbruck, Austria. Kings Coll Hosp London, Kings Coll Sch Med & Dent, London SE5 8RX, England. Med Univ Innsbruck, Dept Urol, Div Pediat Urol, Innsbruck, Austria. Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. Med Univ Vienna, Dept Internal Med 4, Vienna, Austria. Univ Sheffield, Dept Child Hlth, Sheffield, S Yorkshire, England. UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & HTA, Hall In Tirol, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessmnet, Boston, MA 02115 USA. UMIT Univ Hlth Sci Med Informat & Technol, Inst Med Law Human Resources & Hlth Polit, Hall In Tirol, Austria. RP Dhawan, A (reprint author), Kings Coll Hosp London, Paediat Liver Ctr, Denmark Hill, London SE5 8RX, England. EM anil.dhawan@kcl.ac.uk RI Kronenberg, Florian/B-1736-2008; Dhawan, Anil/B-6730-2009 OI Kronenberg, Florian/0000-0003-2229-1120; NR 19 TC 33 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD AUG PY 2007 VL 47 IS 2 BP 270 EP 276 DI 10.1016/j.jhep.2007.03.011 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 198QK UT WOS:000248642400015 PM 17449133 ER PT J AU Pascal, V Yamada, E Martin, MP Alter, G Altfeld, M Metcalf, JA Baseler, MW Adelsberger, JW Carrington, M Anderson, SK McVicar, DW AF Pascal, Veronique Yamada, Eriko Martin, Maureen P. Alter, Galit Altfeld, Marcus Metcalf, Julia A. Baseler, Michael W. Adelsberger, Joseph W. Carrington, Mary Anderson, Stephen K. McVicar, Daniel W. TI Detection of KIR3DS1 on the cell surface of peripheral blood NK cells facilitates identification of a novel null allele and assessment of KIR3DS1 expression during HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; IG-LIKE RECEPTORS; C-VIRUS-INFECTION; ACTIVATING RECEPTORS; T-CELLS; HLA-B; INHIBITORY RECEPTORS; SELECTIVE DEPLETION; GENE FAMILIES AB KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles described, including its activating counterpart, KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in individuals expressing HLA-Bw4 with isoleucine at position 80. However, due to the lack of a specific All, KIR3DS1 expression and function is not well characterized. In this study, we demonstrate KIR3DS1 expression on a substantial subset of peripheral natural killer cells through its recognition by the mAb Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Interestingly, KIR3DS1 is also expressed by a small proportion of CD56(+) T cells. We show that ligation of KIR3DS1 by Z27 leads to NK cell IFN-gamma production and degranulation as assessed by expression of CD107a. Furthermore, we document the persistence of KIR3DS1(+) NK cells in HIV-1 viremic patients. The high frequency of KIR3DS1 expression, along with its ability to activate NK cells, and its maintenance during HIV-1 viremia are consistent with the epidemiological data suggesting a critical role for this receptor in controlling HIV-1 pathogenesis. C1 NCI, Ctr Canc Res, Expt Immunol Lab, Canc Inflammat Program, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit,Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Natl Inst Hlth, NIAID, Div Clin Res, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Clin Serv Program, AIDS Monitoring Lab, Frederick, MD 21702 USA. RP McVicar, DW (reprint author), NCI, Ctr Canc Res, Expt Immunol Lab, Canc Inflammat Program, Bldg 560 Room 31-46, Frederick, MD 21702 USA. EM mcvicar@nih.gov RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; FU Intramural NIH HHS; NIAID NIH HHS [1 R01 AI067031-01A2]; PHS HHS [N01-C0-12400] NR 52 TC 39 Z9 39 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1625 EP 1633 PG 9 WC Immunology SC Immunology GA 194BU UT WOS:000248319700026 PM 17641029 ER PT J AU Touma, M Antonini, V Kumar, M Osborn, SL Bobenchik, AM Keskin, DB Connolly, JE Grusby, MJ Reinherz, EL Clayton, LK AF Touma, Maki Antonini, Valeria Kumar, Manoj Osborn, Stephanie L. Bobenchik, April M. Keskin, Derin B. Connolly, John E. Grusby, Michael J. Reinherz, Ellis L. Clayton, Linda K. TI Functional role for I kappa BNS in T cell cytokine regulation as revealed by targeted gene disruption SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED IL-6 PRODUCTION; C-REL; NUCLEAR-FACTOR; NEGATIVE SELECTION; TRANSCRIPTIONAL ACTIVATION; LYMPHOCYTE-PROLIFERATION; INTERLEUKIN-2 EXPRESSION; RESPONSE ELEMENTS; ANTIGEN RECEPTOR; B PROTEIN AB Triggering of the TCR by cognate peptide/MHC ligands induces expression Of I kappa BNS, a member of the IKB family of NF-kappa B inhibitors whose expression is associated with apoptosis of immature thymocytes. To understand the role Of I kappa BNS in TCR triggering, we created a targeted disruption of the I kappa BNS gene. Surprisingly, mice lacking I kappa BNS show normal thymic progression but both thymocytes and T cells manifest reduced TCR-stimulated proliferation. Moreover, I kappa KBNS knockout thymocytes and T cells produce significantly less IL-2 and IFN-gamma than wild-type cells. Transfection analysis demonstrates that I kappa BNS and c-Rel individually increase IL-2 promoter activity. The effect of I kappa BNS on the IL-2 promoter, unlike c-Rel, is dependent on the NF-kappa B rather than the CD28RE site; mutation of the NF-kappa B site extinguishes the induction of transcription by I kappa BNS in transfectants and prevents association of I-kappa BNS with IL-2 promoter DNA. Microarray analyses confirm the reduction in IL-2 production and some IFN-gamma-linked transcripts in I kappa BNS knockout T cells. Collectively, our findings demonstrate that I kappa BNS regulates production of IL-2 and other cytokines induced via "strong" TCR ligation. C1 Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Baylor Inst Immunol Res, Dallas, TX 75204 USA. RP Clayton, LK (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM linda_clayton@dfci.harvard.edu RI Connolly, John/B-8099-2014 FU NIAID NIH HHS [AI19807, AI51779] NR 61 TC 23 Z9 26 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 AUG 1 PY 2007 VL 179 IS 3 BP 1681 EP 1692 PG 12 WC Immunology SC Immunology GA 194BU UT WOS:000248319700031 PM 17641034 ER PT J AU Thomas, SY Banerji, A Medoff, BD Lilly, CM Luster, AD AF Thomas, Seddon Y. Banerji, Aleena Medoff, Benjamin D. Lilly, Craig M. Luster, Andrew D. TI Multiple chemokine receptors, including CCR6 and CXCR3, regulate antigen-induced T cell homing to the human asthmatic airway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; SEGMENTAL ALLERGEN CHALLENGE; ATOPIC ASTHMA; TH2 CELLS; EOTAXIN EXPRESSION; PERIPHERAL-TISSUES; CYTOKINE PROFILE; EPITHELIAL-CELLS; BRONCHIAL-ASTHMA; GENE-EXPRESSION AB Human allergic asthma is a chronic inflammatory disease of the airways thought to be driven by allergen-specific Th2 cells, which are recruited into the lung in response to inhaled allergen. To identify chemoattractant receptors that control this homing pattern, we used endobronchial segmental allergen challenge in human atopic asthmatics to define the pattern of chemoattractant receptor expression on recruited T cells as well as the numbers of recruited CD1d-restricted NKT cells and levels of chemokines in the bronchoalveolar (BAL) fluid. CD1d-restricted NKT cells comprised only a small minority of BAL T cells before or after Ag challenge. BAL T cells were enriched in their expression of specific chemoattractant receptors compared with peripheral blood T cells prechallenge, including CCR5, CCR6, CXCR3, CXCR4, and BLT1. Surprisingly, following segmental allergen challenge, no chemoattractant receptor was specifically increased. However, CCR6 and CXCR3, which were expressed on virtually all CD4(+) BAL T cells prechallenge, were markedly decreased on all recruited BAL T cells following Ag challenge, suggesting that these receptors were internalized following encounter with ligand in the airway. Our data therefore suggests a role for CCR6 and CXCR3, in conjunction with other chemoattractant receptors, in the recruitment of inflammatory T cells into the BAL during the allergic asthmatic response. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Bldg 149-8301,13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU NIAID NIH HHS [R01 AI40618, T32 AI060548] NR 54 TC 59 Z9 60 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1901 EP 1912 PG 12 WC Immunology SC Immunology GA 194BU UT WOS:000248319700054 PM 17641057 ER PT J AU Kong, TQ Scully, M Shelley, CS Colgan, SP AF Kong, Tianqing Scully, Melanie Shelley, C. Simon Colgan, Sean P. TI Identification of pur alpha as a new hypoxia response factor responsible for coordinated induction of the beta(2) integrin family SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; BETA(2) LEUKOCYTE INTEGRIN; INDUCIBLE FACTOR-I; CELL-LINE U937; TRANSCRIPTION FACTORS; BINDING-PROTEIN; CD11B PROMOTER; GENE PROMOTER; IMMUNE-SYSTEM; MYELOID CELLS AB Central to the process of inflammation are hypoxic conditions that lead to the binding of circulating leukocytes to the endothelium. We have previously shown that such binding is mediated by monocytes being able to directly sense hypoxic conditions and respond by inducing their surface expression of the beta(2) integrin family of adhesion molecules. In this study, we show that coordinated induction of the beta(2) integrins during direct hypoxia-sensing occurs through transcriptional activation of each of the genes by which they are encoded. Certain of the molecular mechanisms that mediate this activation in transcription are dependent upon hypoxia-inducible factor-1 (HIF-1), whereas others are HIF-1 independent. In search of these HIF-1-independent mechanisms, we identified Pur alpha as a new hypoxia-response factor. Binding of Pura to the HIF-1-independent beta(2) integrin promoters is induced by hypoxia and mutagenesis of these Pur alpha-binding sites almost completely abolishes the ability of the promoters to respond to hypoxic conditions. Additional studies using siRNA directed against Pura also revealed a loss in the hypoxic response of the beta(2) integrin promoters. Taken together, our findings demonstrate that hypoxia induces a coordinated up-regulation in beta(2) integrin expression that is dependent upon transcriptional mechanisms mediated by HIF-1 and Pur alpha. C1 Univ Colorado, Hlth Sci Ctr, Div Gastroenterol, Mucosal Inflammat Program, Denver, CO 80218 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. RP Colgan, SP (reprint author), Univ Colorado, Hlth Sci Ctr, Div Gastroenterol, Mucosal Inflammat Program, Denver, CO 80218 USA. EM shelley@receptor.mgh.harvard.edu; sean.colgan@uchsc.edu RI Colgan, Sean/B-4573-2009 FU NHLBI NIH HHS [HL60569]; NIDCR NIH HHS [DE016191]; NIDDK NIH HHS [DK50189] NR 47 TC 18 Z9 19 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2007 VL 179 IS 3 BP 1934 EP 1941 PG 8 WC Immunology SC Immunology GA 194BU UT WOS:000248319700057 PM 17641060 ER PT J AU Dimmock, P Zhang, Q Shieh, J Chou, PC Truong, C Schmitt, E Sifry-Platt, M Ficicioglu, C Enns, G Arch, E Longo, N Lipson, M Vallance, H Craigen, WJ Wong, LJ AF Dimmock, P. Zhang, Q. Shieh, J. Chou, P. C. Truong, C. Schmitt, E. Sifry-Platt, M. Ficicioglu, C. Enns, G. Arch, E. Longo, N. Lipson, M. Vallance, H. Craigen, W. J. Wong, L. J. TI Deoxyguanosine kinase deficiency: Two diseases or one? SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Calif San Francisco, J Davi Gladstone Inst, San Francisco, CA 94143 USA. Kaiser Permanente, Sacramento, CA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2007 VL 30 SU 1 BP 79 EP 79 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 201VF UT WOS:000248860000313 ER PT J AU de Halac, IN Cismondi, I Kohan, R de Kremer, R D Guelbert, N Muller, VJ Creegan, D Canelli, N Aiello, CH Anzolini, VT Mole, S Xin, W Sims, K Fietz, M Santorelli, FM de Ramirez, AMO AF de Halac, I Noher Cismondi, I Kohan, R. Dodelson de Kremer, R. Guelbert, N. Muller, V. J. Creegan, D. Canelli, N. Aiello, C. H. Tapia Anzolini, V Mole, S. Xin, W. Sims, K. Fietz, M. Santorelli, F. M. Oller de Ramirez, A. M. TI Characterization of neuronal ceroid lipofuscinoses in Argentina SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Consejo Nacl Invest Cient & Tecn, RA, Cordoba, Argentina. Univ Nacl Cordoba, Fac Odont, RA-5000 Cordoba, Argentina. Univ Nacl Cordoba, CEMECO, RA-5000 Cordoba, Argentina. Youth Womens Hlth Serv, Dept Med Genet, Adelaide, SA, Australia. Great Ormond St Hosp Sick Children, Mol Gen Lab, London WC1N 3JH, England. IRCCS Bambino Gesu Hosp, Rome, Italy. Massachusetts Gen Hosp, Neurogenet DNA Diagn Lab, Boston, MA 02114 USA. RI Mole, Sara/C-2024-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2007 VL 30 SU 1 BP 103 EP 103 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 201VF UT WOS:000248860000409 ER PT J AU Iuga, AO Lerner, EA AF Iuga, Aurel O. Lerner, Ethan A. TI TRP-ing up melanophores: TRPM7, melanin synthesis, and pigment cell survival SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID ZEBRAFISH; MELANOCYTES; TOUCHTONE AB McNeill et al. (2007, this issue) dissect the potential role of TRPM7 ion channels in pigment cells by studying the phenotype of zebrafish trpm7 mutant embryos. They demonstrate that 1-phenyl-2-thiourea, a known melanin synthesis inhibitor, prevents melanophore cell death in these mutants. This suggests a potential functional link between TRPM7 signaling and the detoxification of melanin synthesis intermediates. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Lerner, EA (reprint author), Bldg 149,St 13, Charlestown, MA 02129 USA. EM ethan.lerner@cbrc2.mgh.harvard.edu NR 9 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2007 VL 127 IS 8 BP 1855 EP 1856 DI 10.1038/sj.jid.5700773 PG 2 WC Dermatology SC Dermatology GA 197XT UT WOS:000248591200013 PM 17632567 ER PT J AU Sun, PZ AF Sun, Phillip Zhe TI Improved diffusion measurement in heterogeneous systems using the magic asymmetric gradient stimulated echo (MAGSTE) technique SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE background gradient; bPGSTE; diffusion; inhomogeneity; MAGSTE; porous media; pulsed field gradient ID TO-VOLUME RATIO; FIELD-GRADIENT; POROUS-MEDIA; NMR-DIFFUSION; RESTRICTED DIFFUSION; SURFACE RELAXIVITY; SEDIMENTARY-ROCKS; MAGNETIC-FIELD; GAS-DIFFUSION; XENON GAS AB A magic asymmetric gradient stimulated echo (MAGSTE) sequence was recently proposed to improve molecular diffusion measurements in the presence of spatially varying background gradients. Its effectiveness has been demonstrated previously with simulated background gradients and in phantoms that contain bulk susceptibility differences. In this study, we investigated the MAGSTE technique in microscopically heterogeneous systems, and compared it with the conventional bipolar pulsed gradient stimulated echo (bPGSTE) sequence. We demonstrated that the MASGTE measurements, compared to the bPGSTE method, varied significantly less when the diffusion encoding/decoding interval (8) was changed. In addition, the MAGSTE technique provided good characterization of the surface area-to-volume ratio for heterogeneous systems investigated in this study. In sum, this study showed that the MAGSTE technique provided diffusion measurements superior to those of the bPGSTE sequence, especially in the presence of severe heterogeneous background gradients. (c) 2007 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. Kennedy Krieger Inst, FM Kirby Res Inst Brain Imaging, Baltimore, MD 21205 USA. RP Sun, PZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU NIBIB NIH HHS [R01 EB002634, R01 EB002634-14]; NINDS NIH HHS [R01 NS038477, R01 NS038477-09] NR 27 TC 11 Z9 12 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 EI 1096-0856 J9 J MAGN RESON JI J. Magn. Reson. PD AUG PY 2007 VL 187 IS 2 BP 177 EP 183 DI 10.1016/j.jmr.2007.04.011 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 196DV UT WOS:000248462800001 PM 17500019 ER PT J AU Sosnovik, DE Dai, G Nahrendorf, M Rosen, BR Seethamraju, R AF Sosnovik, David E. Dai, Guangping Nahrendorf, Matthias Rosen, Bruce R. Seethamraju, Ravi TI Cardiac MRI in mice at 9.4 tesla with a transmit-receive surface coil and a cardiac-tailored intensity-correction algorithm SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; cardiac; mouse; surface coil; sensitivity correction ID MYOCARDIAL-INFARCTION; IN-VIVO; CONTRACTILE DYSFUNCTION; HUMAN BRAIN; MOUSE; ARRAY; IMAGES; HEART; RECONSTRUCTION; NONUNIFORMITY AB Purpose: To evaluate the use of a transmit-receive surface (TRS) coil and a cardiac-tailored intensity-correction algorithm for cardiac MRI in mice at 9.4 Tesla (9.4T). Materials and Methods: Fast low-angle shot (FLASH) clues, with and without delays alternating with nutations for tailored excitation (DANTE) tagging, were acquired in 13 mice. An intensity-correction algorithm was developed to compensate for the sensitivity profile of the surface coil, and was tailored to account for the unique distribution of noise and flow artifacts in cardiac MR images. Results: Image quality was extremely high and allowed fine structures such as trabeculations, valve cusps, and coronary arteries to be clearly visualized. The tag lines created with the surface coil were also sharp and clearly visible. Application of the intensity-correction algorithm improved signal intensity, tissue contrast, and image quality even further. Importantly, the cardiac-tailored properties of the correction algorithm prevented noise and flow artifacts from being significantly amplified. Conclusion: The feasibility and value of cardiac MRI in mice with a TRS coil has been demonstrated. In addition, a cardiac-tailored intensity-correction algorithm has been developed and shown to improve image quality even further. The use of these techniques could produce significant potential benefits over a broad range of scanners, coil configurations, and field strengths. C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02115 USA. USA Inc, Stemens Med Cardiol, Malvern, PA USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.hanard.edu FU NCRR NIH HHS [P41RR14075]; NHLBI NIH HHS [K08-HL079984] NR 22 TC 14 Z9 14 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2007 VL 26 IS 2 BP 279 EP 287 DI 10.1002/jmri.20966 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197SX UT WOS:000248577900007 PM 17654729 ER PT J AU Chenine, AL Shai-Kobiler, E Steele, LN Augostini, P Lee, SJ Ruprecht, RM Secor, WE AF Chenine, Agens-Laurence Shai-Kobiler, Ela Steele, Lisa N. Augostini, Peter Lee, Sandra J. Ruprecht, Ruth M. Secor, W. Evan TI Schistosoma mansoni increases mucosal aids virus transmission and replication in nonhuman primates SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 2007 VL 36 IS 4-5 MA 16 BP 292 EP 292 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700030 ER PT J AU Gauduin, MC Yu, Y Gillis, J Johnson, RP AF Gauduin, Marie-Claire Yu, Yi Gillis, Jacqueline Johnson, R. Paul TI Trafficking of SIV-specific effector memory CD4+T lymphocytes to lymphoid and extralymphoid sites in macaques infected with live attenuated SIV SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, New England Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 52 BP 306 EP 306 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700066 ER PT J AU Tokumoto, Y Hiasa, Y Horiike, N Michitaka, K Matsuura, B Chung, RT Onji, M AF Tokumoto, Yoshio Hiasa, Yoichi Horiike, Norio Michitaka, Kojiro Matsuura, Bunzo Chung, Raymond T. Onji, Morikazu TI Hepatitis C virus expression and interferon antiviral action is dependent on PKR expression SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE small interfering RNA (siRNA); eukaryotic initiation factor-2 alpha(elF2 alpha); BT7-H; Huh-T7 ID PROTEIN-KINASE PKR; CAP-INDEPENDENT TRANSLATION; MONKEY KIDNEY-CELLS; GENE-EXPRESSION; SUBGENOMIC REPLICONS; RNA REPLICATION; A VIRUS; INFECTION; ALPHA; MECHANISM AB Interferon (IFN)-inducible double-stranded RNA-activated protein kinase (PKR) is thought to play a key antiviral role against hepatitis C virus (HCV). However, demonstrating the importance of PKR expression on HCV protein synthesis in the presence or absence of IFN has proven difficult in vivo. In the present experiment, full-length HCV constructs were transiently transfected into two cell lines stably expressing T7 RNA polymerase. HCV expression was monitored under conditions of upregulated or downregulated PKR expression. In addition, IFN was monitored during downregulation of PKR. HCV expression effectively increased PKR expression, as well as that of its regulated proteins. PKR was obviously knocked down by PKR-specific siRNA, which resulted in significantly increased HCV core protein levels. Conversely, over-expression of PKR significantly suppressed HCV core levels in both cell lines. Furthermore, IFN induced high levels of PKR, whereas downregulation of PKR reversed IFN's antiviral effects and increased HCV core levels. Based on these results, it appears that HCV protein expression is directly dependent on PKR expression. PKR is antiviral toward HCV and responsible for IFN's effect against HCV. C1 Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Toon, Ehime 7910295, Japan. Ehime Univ, Dept Endoscop Med, Sch Med, Toon, Ehime, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hiasa, Y (reprint author), Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Toon, Ehime 7910295, Japan. EM hiasa@m.ehime-u.ac.jp FU NIDDK NIH HHS [DK57857] NR 38 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD AUG PY 2007 VL 79 IS 8 BP 1120 EP 1127 DI 10.1002/jmv.20902 PG 8 WC Virology SC Virology GA 184LF UT WOS:000247642200012 PM 17596833 ER PT J AU Tsuang, MT Simpson, JC Koenen, KC Kremen, WS Lyons, MJ AF Tsuang, Ming T. Simpson, John C. Koenen, Karestan C. Kremen, William S. Lyons, Michael J. TI Spiritual well-being and health SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE religion; mental health; spiritual well-being; twins ID ERA TWIN REGISTRY; QUALITY-OF-LIFE; FUNCTIONAL ASSESSMENT; CHRONIC ILLNESS; MENTAL-HEALTH; VET REGISTRY; RELIGION; SCALE; CANCER; CONCEPTUALIZATION AB Data on empirical associations between religious variables and health outcomes are needed to clarify the complex interplay between religion and mental health. The aim of this study was to determine whether associations with health variables are primarily attributable to explicitly religious aspects of spiritual well-being (SWB) or to "existential" aspects that primarily reflect a sense of satisfaction or purpose in life. Three hundred forty-five pairs of twins from the Vietnam Era Twin Registry completed a diagnostic interview and questionnaires containing the 2-factor SWB Scale and general health items. Observed associations between SWB and health outcomes were uniquely explained by the SWB subscale of existential well-being, with much less of a unique explanatory contribution from religious well-being or "spiritual involvement." We concluded that studies of SWB and health should continue to distinguish between explicitly religious variables and others that more closely approximate the psychological construct of personal well-being. C1 Univ Calif San Diego, Ctr Behav Gen, Dept Psychiat, La Jolla, CA 92037 USA. Vet Affairs San Diego Healthcare Syst, Psychiat Serv, San Diego, CA USA. Harvard Univ, Sch Publ Hlth, Harvard Inst Psychiat Epidemiol & Genet, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Society, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Human Dev, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Boston Univ, Ctr Med, Dept Psychiat, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Tsuang, MT (reprint author), Univ Calif San Diego, Ctr Behav Gen, Dept Psychiat, Mail Code 0603,9500 Gilman Dr, La Jolla, CA 92037 USA. EM mtsuang@ucsd.edu RI Lyons, Michael/B-6119-2011; Koenen, Karestan/K-5402-2014 OI Lyons, Michael/0000-0001-6516-9219; Koenen, Karestan/0000-0003-3293-4281 FU NIA NIH HHS [R01 AG018386, R01 AG022381] NR 54 TC 26 Z9 26 U1 1 U2 12 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 AUG PY 2007 VL 195 IS 8 BP 673 EP 680 DI 10.1097/NMD.0b013e31811f4062 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 200AJ UT WOS:000248736000007 PM 17700300 ER PT J AU Khan, M Ansari, MA Hoda, NM Giri, S Singh, AK Singh, I AF Khan, M. Ansari, M. A. Hoda, N. M. Giri, S. Singh, A. K. Singh, I. TI Neuroprotection in a rat model of experimental stroke by hydralazine via neutralization of lipid aldehydes SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, 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 AUG PY 2007 VL 102 SU 1 BP 39 EP 40 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600093 ER PT J AU Kauppinen, TM Alano, CC Chan, WY Gan, L Swanson, RA AF Kauppinen, T. M. Alano, C. C. Chan, W. Y. Gan, L. Swanson, R. A. TI ERK2 and minocycline influence neuronal death and microglial activation by regulating PARP-1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA 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 AUG PY 2007 VL 102 SU 1 BP 86 EP 86 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600201 ER PT J AU Khan, M Singh, J Singh, AV Singh, I AF Khan, M. Singh, J. Singh, A. V. Singh, I. TI Modulation of plasmalogen metabolism by lovastatin: Implications for cerebral adrenoleukodystrophy SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, 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 AUG PY 2007 VL 102 SU 1 BP 147 EP 147 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600353 ER PT J AU Lopez-Meraz, ML Niquet, J Wasterlain, CG AF Lopez-Meraz, M. L. Niquet, J. Wasterlain, C. G. TI Caspase-8 and caspase-3 may contribute to status epilepticus-induced neuronal necrosis in the immature brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 AUG PY 2007 VL 102 SU 1 BP 219 EP 219 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600519 ER PT J AU Conklin, SM Runyan, CA Leonard, S Reddy, RD Yao, JK AF Conklin, S. M. Runyan, C. A. Leonard, S. Reddy, R. D. Yao, J. K. TI Abnormal polyunsaturated fatty acids in postmortem brains of patients with depression SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. MIT, Cambridge, MA 02139 USA. Denver VA Med Ctr, Denver, CO 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 AUG PY 2007 VL 102 SU 1 BP 230 EP 230 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600552 ER PT J AU Hogan, PG Feske, S Gwack, Y Prakriya, M Rao, A AF Hogan, P. G. Feske, S. Gwack, Y. Prakriya, M. Rao, A. TI Role of a Ca2+ entry channel, the CRAC channel, in cell function SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 238 EP 238 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600568 ER PT J AU Messamore, E Yao, JK AF Messamore, E. Yao, J. K. TI Niacin sensitivity and arachidonic acid in schizophrenia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Portland VA Med Ctr, Portland, OR USA. VA Pittsburhg Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 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 AUG PY 2007 VL 102 SU 1 BP 270 EP 270 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600647 ER PT J AU Vandenbark, AA Burrows, GG Offner, H Link, J AF Vandenbark, A. A. Burrows, G. G. Offner, H. Link, J. TI From EAE to MS clinical trial: DR2/MOG-35-55 recombinant T cell receptor ligand (RTL) treats relapse of EAE in DR2 transgenic mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 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 AUG PY 2007 VL 102 SU 1 BP 290 EP 290 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600697 ER PT J AU Balcioglu, A Kim, MO Sharma, N Cha, JH Breakefield, XO Standaert, DG AF Balcioglu, Aygul Kim, Mee-Ohk Sharma, Nutan Cha, Jang-Ho Breakefield, Xandra O. Standaert, David G. TI Dopamine release is impaired in a mouse model of DYT1 dystonia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; DYT1 dystonia; HPLC; in vivo microdialysis; mouse; striatum ID PRIMARY TORSION DYSTONIA; EARLY-ONSET DYSTONIA; MUTATION; GENE; BRAIN; MICE; PROTEIN; MICRODIALYSIS; AMPHETAMINE; RECEPTORS AB Early onset torsion dystonia, the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein torsinA. This form of dystonia is referred to as DYT1. We have used a transgenic mouse model of DYT1 dystonia [human mutant-type (hMT)1 mice] to examine the effect of the mutant human torsinA protein on striatal dopaminergic function. Analysis of striatal tissue dopamine (DA) and metabolites using HPLC revealed no difference between hMT1 mice and their non-transgenic littermates. Pre-synaptic DA transporters were studied using in vitro autoradiography with [H-3]mazindol, a ligand for the membrane DA transporter, and [H-3]dihydrotetrabenazine, a ligand for the vesicular monoamine transporter. No difference in the density of striatal DA transporter or vesicular monoamine transporter binding sites was observed. Post-synaptic receptors were studied using [H-3]SCH-23390, a ligand for D-1 class receptors, [H-3]YM-09151-2 and a ligand for D-2 class receptors. There were again no differences in the density of striatal binding sites for these ligands. Using in vivo microdialysis in awake animals, we studied basal as well as amphetamine-stimulated striatal extracellular DA levels. Basal extracellular DA levels were similar, but the response to amphetamine was markedly attenuated in the hMT1 mice compared with their non-transgenic littermates (253 +/- 71% vs. 561 +/- 132%, p < 0.05, two-way ANOVA). These observations suggest that the mutation in the torsinA protein responsible for DYT1 dystonia may interfere with transport or release of DA, but does not alter pre-synaptic transporters or postsynaptic DA receptors. The defect in DA release as observed may contribute to the abnormalities in motor learning as previously documented in this transgenic mouse model, and may contribute to the clinical symptoms of the human disorder. C1 Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Mol Neurogenet Unit, Dept Neurol & Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. RP Balcioglu, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Room 6101,Bldg 149,13th St, Charlestown, MA 02129 USA. EM abalcioglu@partners.org OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS37409, P01 NS037409] NR 37 TC 68 Z9 68 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 3 BP 783 EP 788 DI 10.1111/j.1471-4159.2007.04590.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 196TD UT WOS:000248504200020 PM 17550429 ER PT J AU Garcia-Alloza, M Borrelli, LA Rozkalne, A Hyman, BT Bacskai, BJ AF Garcia-Alloza, M. Borrelli, L. A. Rozkalne, A. Hyman, B. T. Bacskai, B. J. TI Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer; curcumin; imaging; multiphoton; neuritic dystrophy; senile plaque ID A-BETA PEPTIDE; TRANSGENIC MICE; MULTIPHOTON MICROSCOPY; OXIDATIVE STRESS; DISEASE; MICROGLIA; ABNORMALITIES; DEPOSITION; PROTEIN; BRAIN AB Alzheimer's disease (AD) is characterized by senile plaques and neuroclegeneration although the neurotoxic mechanisms have not been completely elucidated. It is clear that both oxidative stress and inflammation play an important role in the illness. The compound curcumin, with a broad spectrum of anti-oxidant, anti-inflammatory, and anti-fibrilogenic activities may represent a promising approach for preventing or treating AD. Curcumin is a small fluorescent compound that binds to amyloid deposits. In the present work we used in vivo multi-photon microscopy (MPM) to demonstrate that curcumin crosses the blood-brain barrier and labels senile plaques and cerebrovascular amyloid angiopathy (CAA) in APPswe/ PS1dE9 mice. Moreover, systemic treatment of mice with curcumin for 7 days clears and reduces existing plaques, as monitored with longitudinal imaging, suggesting a potent disaggregation effect. Curcumin also led to a limited, but significant reversal of structural changes in dystrophic dendrites, including abnormal curvature and dystrophy size. Together, these data suggest that curcurnin reverses existing amyloid pathology and associated neurotoxicity in a mouse model of AD. This approach could lead to more effective clinical therapies for the prevention of oxidative stress, inflammation and neurotoxicity associated with AD. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, Charlestown, MA USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, Charlestown, MA USA. EM bbacskai@partners.org OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG020570, AG024688, AG08487]; NIBIB NIH HHS [EB000768] NR 46 TC 267 Z9 280 U1 3 U2 27 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 4 BP 1095 EP 1104 DI 10.1111/j.1471-4159.2007.04613.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 202EF UT WOS:000248884100010 PM 17472706 ER PT J AU Elder, GA Cho, JY English, DF Franciosi, S Schmeldler, J Sosa, MAG De Gasperi, R Fisher, EA Mathews, PM Haroutunian, V Buxbaum, JD AF Elder, Gregory A. Cho, Julie Y. English, Daniel F. Franciosi, Sonia Schmeldler, James Sosa, Miguel A. Gama De Gasperi, Rita Fisher, Edward A. Mathews, Paul M. Haroutunian, Vahram Buxbaum, Joseph D. TI Elevated plasma cholestrol does not affect brain A beta in mice lacking the low-density lipoprotein receptor SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; Apolipoprotein E; dietary cholesterol and fat; low-density lipoprotein receptor; null mutation ID TRANSGENIC MOUSE MODEL; DIET-INDUCED HYPERCHOLESTEROLEMIA; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; KNOCKOUT MICE; LEARNING-DEFICITS; PLAQUE-FORMATION; MESSENGER-RNA AB Epidemiological studies support an association between vascular risk factors, including hypercholesterolernia, and Alzheimer's disease (AD). Recently, there has been much interest in the possibility that hypercholesterolernia might directly promote P-amyloid (A beta) production. Indeed, in vitro studies have shown that increasing cellular cholesterol levels enhances AP production. However, studies in AD transgenic mouse models have not consistently found that elevated plasma cholesterol leads to increased AP production or deposition in vivo. In this study, we determined whether elevated peripheral cholesterol influences AP production in mice with a null mutation of the low-density lipoprotein receptor (LDLR). We show that dramatically elevated plasma cholesterol levels, whether induced by high cholesterol, high fat, or high fat/high cholesterol diets, did not affect either levels of brain AP40, A beta 42, or APP, or the A beta 42/40 or APP-CTF/APP ratios, nor substantially alter brain cholesterol levels. ApoE protein levels in brain were, however, elevated, in LDLR-/mice by post-transcriptional mechanisms. Collectively, these studies argue that plasma cholesterol levels do not normally regulate production of brain A beta. 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. CUNY Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Biomath Sci, New York, NY 10029 USA. Vet Affairs Med Ctr, James J Peters Dept, Res & Dev Serv, Bronx, NY USA. CUNY Mt Sinai Sch Med, Lab Mol Neuropsychiat, New York, NY 10029 USA. NYU, Sch Med, Dept Med, Leon H Charney Div,Marc & Ruti Vasc Biol Program, New York, NY USA. Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. RP Buxbaum, JD (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu FU NHLBI NIH HHS [HL084312]; NIA NIH HHS [AG010491, AG002219, AG017617] NR 58 TC 23 Z9 24 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 IS 4 BP 1220 EP 1231 DI 10.1111/j.1471-4159.2007.04614.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 202EF UT WOS:000248884100021 PM 17472705 ER PT J AU Jho, DH Neckrysh, S Hardman, J Charbel, FT Amin-Hanjani, S AF Jho, David H. Neckrysh, Sergey Hardman, Julian Charbel, Fady T. Amin-Hanjani, Sepideh TI Ethylene oxide gas sterilization: a simple technique for storing explanted skull bone - Technical note SO JOURNAL OF NEUROSURGERY LA English DT Article DE decompressive craniectomy; ethylene oxide; skull bone flap; sterilization ID MASSACHUSETTS HOSPITALS; DELAYED CRANIOPLASTY; INFECTION-RATES; FLAPS; CRANIOTOMY; FROZEN; PRESERVATION; STANDARD; SCALP AB The authors evaluated the effectiveness of a simple technique using ethylene oxide (EtO) gas sterilization and room temperature storage of autologous bone grafts for reconstructive cranioplasty following decompressive craniectomy. The authors retrospectively analyzed data in 103 consecutive patients who underwent cranioplasty following decompressive craniectomy for any cause at the University of Illinois at Chicago between 1999 and 2005. Patients with a preexisting intracranial infection prior to craniectomy or lost to follow-up before reconstruction were excluded. Autologous bone grafts were cleansed of soft tissue, hermetically sealed in sterilization pouches for EtO gas sterilization, and stored at room temperature until reconstructive cranioplasty was performed. Cranioplasties were performed an average of 4 months after decompressive craniectomy, and the follow-up after reconstruction averaged 14 months. Excellent aesthetic and functional results after single-stage reconstruction were achieved in 95 patients (92.2%) as confirmed on computed tomography. An infection of the bone flap occurred in eight patients (7.8%), and the skull defects were eventually reconstructed using polymethylmethacrylate with satisfactory results. The mean preservation interval was 3.8 months in patients with uninfected flaps and 6.4 months in those with infected flaps (p = 0.02). A preservation time beyond 10 months was associated with a significantly increased risk of flap infection postcranioplasty (odds ratio [OR] 10.8, p = 0.02). Additionally, patients who had undergone multiple craniotomies demonstrated a trend toward increased infection rates (OR 3.0, p = 0. 13). Data in this analysis support the effectiveness of this method, which can be performed at any institution that provides EtO gas sterilization services. The findings also suggest that bone flaps preserved beyond 10 months using this technique should be discarded or resterilized prior to reconstruction. C1 Univ Illinois, Dept Neurosurg, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Amin-Hanjani, S (reprint author), Univ Illinois, Dept Neurosurg, 912 S Wood St,M-C 799, Chicago, IL 60612 USA. EM hanjani@uic.edu NR 31 TC 17 Z9 18 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2007 VL 107 IS 2 BP 440 EP 445 DI 10.3171/JNS-07/08/0440 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 196XT UT WOS:000248517300030 PM 17695404 ER PT J AU Goody, RJ Beckham, JD Rubtsova, K Tyler, KL AF Goody, Robin J. Beckham, J. David Rubtsova, Kira Tyler, Kenneth L. TI JAK-STAT signaling pathways are activated in the brain following reovirus infection SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE apoptosis; Janus-activated kinase; reovirus; signal transducer and activator of transcription; viral encephalitis ID CENTRAL-NERVOUS-SYSTEM; EPIDERMAL-GROWTH-FACTOR; GENE-EXPRESSION; MONOCLONAL-ANTIBODIES; TARGETED DISRUPTION; INDUCED APOPTOSIS; INTERFERON-GAMMA; INJURY; TRANSCRIPTION; INHIBITION AB Reovirus infection provides a classic experimental model system for studying the pathogenesis of viral infections of the central nervous system (CNS), with apoptosis acting as the major mechanism of cell death. The authors have examined the role of signal transducer and activator of transcription (STAT)1, a component of Janus-activated kinase (JAK)-STAT signaling, a pathway implicated in antiviral responses and pathways regulating apoptosis, following reovirus infection. Infection of primary cortical neuron cultures with reovirus serotype 3 strain Abney (T3A) resulted in phosphorylation of STAT1 at sites critical for transcriptional activity. Activated STAT1 was also detected in the brain of neonatal mice following T3A infection, with a nuclear pattern of expression in areas of virus-induced injury. Activation of STAT proteins is typically mediated by JAKs. The authors observed JAK2 phosphorylation (Tyr 1007/1008) in brain lysates from T3A-infected mice. Inhibition of JAK activity with the inhibitor AG-490 blocked reovirus-induced STAT1 activation in neuronal cultures, indicating reovirus-induced 'TAT activation is JAK dependent. Pretreatment of neuronal cultures with antibody raised against interferon (IFN)-alpha/beta R2 inhibited T3A-induced STAT1 phosphorylation, whereas neither IFN-gamma or IFN-gamma R2 antibody pretreatment had any effect on T3A-induced STAT1 phosphorylation. Mice lacking the STAT1 gene demonstrated increased susceptibility to reovirus infection, with increased mortality and higher viral titers in the brain compared to wild-type animals. The results demonstrate activation of a type I IFN-mediated, JAK-dependent STAT signaling pathway following reovirus infection and suggest that STAT1 is a key component of host defense mechanisms against reovirus infection in the brain. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E Ninth Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [1R01NS051403, 5R01NS050138, R01 NS050138, R01 NS050138-04, R01 NS051403, R01 NS051403-03] NR 35 TC 21 Z9 22 U1 0 U2 0 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 AUG PY 2007 VL 13 IS 4 BP 373 EP 383 DI 10.1080/13550280701344983 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 210AY UT WOS:000249430300009 PM 17849321 ER PT J AU Graham, AL Cobb, NK Raymond, L Sill, S Young, J AF Graham, Amanda L. Cobb, Nathan K. Raymond, Linda Sill, Stewart Young, Joyce TI Effectiveness of an Internet-based worksite smoking cessation intervention at 12 months SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PUBLIC-HEALTH; CLINICAL-TRIALS; PARTICIPATION; PROGRAM; WORKPLACE; RECOMMENDATIONS; ABSTINENCE; DEPENDENCE; PROMOTION; QUALITY AB Objective: To evaluate effectiveness of an Internet-based smoking cessation program as pail of a comprehensive health risk reduction initiative in a large, geographically dispersed employee population. Methods: A financial incentive for participation was offered during 2003 health benefits enrollment. The primary cessation outcome was 7-day point prevalence abstinence at 12 months. Results: A total of 1776 employees used the Internet program. Among those surveyed, the response rate was 32%. Quit rates ranged from 13% using intention to treat analysis (nonresponders counted as smokers) to 43% among survey responders. Higher Web site utilization was associated with better cessation outcomes, even after controlling for baseline motivation. Conclusions: The Internet program was successful at reaching a large number of geographically dispersed employees. The range of quit rates suggests that Internet cessation programs can be effective in promoting cessation and preventing relapse in a worksite setting. C1 Georgetown Univ, Med Ctr, Dept Oncol,Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20007 USA. Massachusetts Gen Hosp, Pulm & CC Unit, Boston, MA 02114 USA. MediFit Corp Serv, Norwalk, CT USA. IBM Corp, Durham, NC USA. RP Graham, AL (reprint author), Georgetown Univ, Med Ctr, Dept Oncol,Lombardi Comprehens Canc Ctr, Canc Control Program, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM alg45@georgetown.edu OI Cobb, Nathan/0000-0003-4210-226X; Graham, Amanda/0000-0003-3036-9653 NR 39 TC 52 Z9 53 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 2007 VL 49 IS 8 BP 821 EP 828 DI 10.1097/JOM.0b013e3180d09e6f PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200OF UT WOS:000248772000001 PM 17693778 ER PT J AU Penrod, JD Cortez, T Luhrs, CA AF Penrod, Joan D. Cortez, Therese Luhrs, Carol A. TI Use of a report card to implement a network-based palliative care program SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY AB Objective: To report on implementation of a Veterans Affairs (VA) network-wide, standardized, high-quality palliative care (PC) program using a Web-based PC Report Card for performance monitoring and improvement. Intervention: The PC director and coordinator and facility directors established interdisciplinary teams at five acute care and three nursing home sites. Teams were trained together and subsequently met quarterly for ongoing training. Additionally, the PC director and coordinator developed and implemented a Web-based PC Report Card on the network Intranet for PC coordinator to report performance data monthly to the PC teams. Results: The number of patients in the network who received PC consults more than doubled in the first 4 years of the PC program. The percentage of deaths with PC consultation prior to death increased from 23% in fiscal year (FY) 2002 to 57% in FY06. Over the same period, the average days between the initial PC consultation and patients' death across all sites increased from 23 days to 106 days. Comment: All the sites established PC teams and the number of consultations showed a sustained increase over baseline in 2002. All sites improved on the key process measures captured by the Report Card. C1 James J Peters Vet Affairs Med Ctr, Program Res Serious Mental & Phys Illness, Bronx, NY USA. Vet Affairs New York Healthcare Syst, Brooklyn, NY USA. RP Penrod, JD (reprint author), James J Peters Vet Affairs Med Ctr, Program Res Serious Mental & Phys Illness, Bronx, NY USA. EM joan.penrod@mssm.edu NR 5 TC 4 Z9 4 U1 1 U2 1 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 AUG PY 2007 VL 10 IS 4 BP 858 EP 860 DI 10.1089/jpm.2007.0026 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 207LD UT WOS:000249251700012 PM 17803403 ER PT J AU Sullivan, AM Lakoma, MD Matsuyama, RK Rosenblatt, L Arnold, RM Block, SD AF Sullivan, Amy M. Lakoma, Matthew D. Matsuyama, Robin K. Rosenblatt, Laurie Arnold, Robert M. Block, Susan D. TI Diagnosing and discussing imminent death in the hospital: A secondary analysis of physician interviews SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE-CARE; PALLIATIVE CARE; COMMUNICATING PROGNOSIS; MEDICAL-EDUCATION; CANCER-PATIENTS; DYING PATIENTS; END; FAMILIES; SKILLS; WANT AB Background: Many reports suggest clinicians are often inadequately prepared to "diagnose dying" or discuss the likelihood of imminent death with patients and families. Objective: To describe whether and when physicians report recognizing and communicating the imminence of death and identify potential barriers and facilitators to recognition and communication about dying in the hospital. Methods: Secondary exploratory analysis of interviews with 196 physicians on the medical teams caring for 70 patients who died in the hospital. Results: Although 38% of physicians were unsure on admission the patient would die during this hospitalization, over the course of hospitalization 86% reported knowing death was imminent. Most reported feeling certain days (57%) or hours (18%) before the patient died. Fewer than half of patients, however, were told of the possibility they might die. Communication was most likely to occur for patients who had at least one member of the medical team who was certain that death was imminent, patients who were lucid during their last days, and younger patients. Only 11% of physicians reported personally speaking with patients about the possibility of dying. Physicians who recognized imminent death early and who spoke with patients about the possibility of dying were more likely to report higher satisfaction with end-of-life care provided to patients. Conclusions: Because more than two thirds of patients were unconscious or in and out of lucidity in the last few days of life, waiting for certainty about prognosis may leave little opportunity to help patients and their families prepare for death. Our results identify opportunities for improvement in communication in the face of uncertainty about the imminence of death. In addition to potential benefits to patients and families, these findings suggest that enhancing communication practices may also benefit physicians through increased satisfaction with care and closer connection with those for whom they provide care. C1 Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Virginia Commonwealth Univ, Dept Social & Behav Sci, Richmond, VA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Sullivan, AM (reprint author), Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. EM amy_sullivan@dfci.harvard.edu FU NINR NIH HHS [IR03NR009528] NR 52 TC 33 Z9 33 U1 2 U2 2 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 AUG PY 2007 VL 10 IS 4 BP 882 EP 893 DI 10.1089/jpm.2007.0189 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 207LD UT WOS:000249251700018 PM 17803409 ER PT J AU Abdel-Karim, IA Sammel, RB Prange, MA AF Abdel-Karim, Isam A. Sammel, Robert B. Prange, Mark A. TI Causes of death at autopsy in an inpatient hospice program SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID 3 MEDICAL ERAS AB Background: Although postmortem examination has been reported in a variety of settings and diseases, the medical literature only makes sparse mention of postmortem findings regarding the manner of death in terminally ill patients receiving palliative care. We sought to identify causes of death in an inpatient hospice program as determined by autopsy. Methods: A retrospective chart review of all deaths from January 1998 through June 2000 of the inpatient hospice unit at Audie L. Murphy Veterans Affairs Hospital in San Antonio, Texas, was conducted. Autopsies were routinely offered to survivors of all deceased patients during this period. Basic demographic and clinical characteristics were collected for all patients, and pathologic reports were reviewed. Results: Forty-eight autopsies were conducted out of 260 deaths in the unit (18%). Patients who had autopsies were similar to nonautopsied patients in age, gender, length of stay, presence of cancer and whether this cancer was treated or not. Nonhispanic white patients were more likely to receive an autopsy and African American patients were less likely to receive one (p = 0.027). Most deaths were directly or indirectly related to the primary diagnosis. Pneumonia was present in 79% of all patients (n = 38), and appeared to be the major cause of death in 44% of patients (n = 21). Other deaths were determined to be due to cancer's direct effects, sepsis, ischemic heart disease, hepatic or renal failure, obstructive uropathy, subdural hemorrhage, pulmonary embolism, hypercalcemia and endocarditis. Conclusion: Pneumonia is the most frequent cause of death in patients in this inpatient hospice program. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX 78284 USA. S Texas Vet Affairs Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Abdel-Karim, IA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. EM isamali@yahoo.com NR 14 TC 9 Z9 9 U1 0 U2 1 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 AUG PY 2007 VL 10 IS 4 BP 894 EP 898 DI 10.1089/jpm.2006.0240 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 207LD UT WOS:000249251700019 PM 17803410 ER PT J AU Smith, AK Buss, MK Giansiracusa, DF Block, SD AF Smith, Alexander K. Buss, Mary K. Giansiracusa, David F. Block, Susan D. TI On being fired: Experiences of the patient-initiated termination in palliative medicine relationship in patient-physician SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; DISCUSSING PROGNOSIS; END; ACCOUNTS; TALKING; DOCTORS; CANCER; WANT AB Background: Being "fired" by a patient is an uncomfortable, distressing, and awkward experience for most clinicians. Palliative care clinicians may be at increased risk of termination of the patient-physician relationship for a variety of reasons. Little has been written about the experience of patient-initiated termination of the patient-physician relationship, and to our knowledge, nothing has been written that is specific to palliative care. Objective: To discuss the experience of termination, offer a framework for learning from and coping with the experience, and make recommendations for how to meet patients' needs after the termination. Design: Case study and conceptual analysis of three cases from the experience of a palliative care fellow. Conclusions: The experience of patient-initiated termination of the patient-physician relationship can raise issues of rejection and self-doubt in the palliative care clinician, but can also provide important opportunities for growth, reflection, and learning. In some cases, re-connecting with the patients' families may be appropriate and beneficial for both the clinician and family. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Brookline, MA 02446 USA. Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Maine Med Ctr, Ctr Pain & Palliat Care, Portland, ME 04102 USA. RP Smith, AK (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St, Brookline, MA 02446 USA. EM asmith7@bidmc.harvard.edu NR 27 TC 8 Z9 8 U1 0 U2 1 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 AUG PY 2007 VL 10 IS 4 BP 938 EP 947 DI 10.1089/jpm.2006.0244 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 207LD UT WOS:000249251700026 PM 17803417 ER PT J AU Diaz, A Danon, M Crawford, J AF Diaz, Alejandro Danon, Marco Crawford, John TI McCune-Albright syndrome and disorders due to activating mutations of GNASI SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Review DE McCune-Albright syndrome; cafe-au-lait spots; polyostotic fibrous dysplasia; G protein; precocious puberty; Cushing's syndrome; acromegaly; gigantism; hyperprolactinemia; aromatase inhibitors; bisphosphonates ID POLYOSTOTIC FIBROUS DYSPLASIA; STIMULATORY G-PROTEIN; INDEPENDENT PRECOCIOUS PUBERTY; HORMONE-RELEASING HORMONE; GS-ALPHA MUTATIONS; TERM FOLLOW-UP; GROWTH-HORMONE; PAMIDRONATE TREATMENT; PITUITARY-ADENOMA; PRIMARY HYPERPARATHYROIDISM AB It has been more than seven decades since Drs. Fuller Albright and Donovan McCune published the first reports on individuals with McCune-Albright syndrome (MAS). Since then, the classic triad of precocious puberty, cafe-aulait spots, and polyostotic bone dysplasia continues to define the syndrome. However, having gathered a better picture of the pathophysiology of MAS, the way this condition is understood has changed. Isolated activating mutations of the a subunit of the G protein (GNAS1) have been found in different tissues, including pituitary adenomas, thyroid adenomas, ovarian cysts, monostotic bone dysplasia, and the adrenal glands, to name a few. For this reason, we have added land disorders due to activating mutations of GNAS1' to the title of this review. We discuss here the clinical consequences of GNAS1 activating mutations in different body systems and organs, the diagnostic approach to MAS, and the current therapeutic recommendations. C1 Miami Childrens Hosp, Miami, FL 33155 USA. Cornell Univ, Weill Med Coll, Div Pediat Endocrinol, New York, NY 10021 USA. Massachusetts Gen Hosp, Harvard Med Sch, Cambridge, MA USA. RP Danon, M (reprint author), Miami Childrens Hosp, 3100 SW 62nd Ave, Miami, FL 33155 USA. EM marco.danon@mch.com NR 180 TC 21 Z9 27 U1 1 U2 1 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD AUG PY 2007 VL 20 IS 8 BP 853 EP 880 PG 28 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 214OE UT WOS:000249747100002 PM 17937059 ER PT J AU Goodson, JM Gunsolley, JC Grossi, SG Bland, PS Otomo-Corgel, J Doherty, F Comiskey, J AF Goodson, J. Max Gunsolley, John C. Grossi, Sara G. Bland, Paul S. Otomo-Corgel, Joan Doherty, Frances Comiskey, Judy TI Minocycline HCl microspheres reduce red-complex bacteria in periodontal disease therapy SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE bacteria; dental scaling; drug delivery systems; microbiology; minocycline; periodontitis ID DNA-DNA HYBRIDIZATION; SUBGINGIVAL MICROBIOTA; CLINICAL-TRIAL; CHECKERBOARD; METRONIDAZOLE; ADJUNCT; PLAQUE AB Background: The objective of this trial was to measure the antimicrobial effects of a minocycline HCl microsphere (MM) local drug-delivery system when used as an adjunct to scaling and root planing (SRP). DNA probe analysis for 40 bacteria was used to evaluate the oral bacteria of 127 subjects with moderate to advanced chronic periodontitis. Methods: Subjects were randomly assigned to either SRP alone (N = 65) or MM + SRP (N = 62). The primary endpoints of this study were changes in numbers and proportions of the red-complex bacteria (RCB) and the sum of Porphyromonas gingivalis, Tannerella forsythia (formally T. forsythensis), and Treponema denticola relative to 40 oral bacteria at each test site from baseline to day 30. Numbers of RCB from the five test sites were averaged to provide a value for each subject. Results: MM + SRP reduced the proportion of RCB by 6.49% and the numbers by 9.4 x 10(5). The reduction in RCB proportions and numbers by SRP alone (5.03% and 5.1 X 10(5), respectively) was significantly less. In addition, MM + SRP reduced probing depth by 1.38 mm (compared to 1.01 mm by SRP alone), bleeding on probing was reduced by 25.2% (compared to 13.8% by SRP alone), and a clinical attachment level gain of 1.16 mm (compared to 0.80 mm by SRP alone) was achieved. Conclusion: These observations support the hypothesis that RCBs are responsible for periodontal disease and that local antimicrobial therapy using MM + SRP effectively reduces numbers of RCBs and their proportions to a greater extent than SRP alone. C1 Forsyth Inst, Dept Clin Res, Boston, MA 02115 USA. Virginia Commonwealth Univ, Dept Periodont, Richmond, VA USA. E Carolina Univ, Brody Sch Med, Greenville, NC USA. Univ Tennessee, Coll Dent, Dept Periodont, Memphis, TN USA. Univ Calif Los Angeles, Sch Dent, Dept Periodont, Greater Los Angeles Vet Affairs Healthcare Syst D, Los Angeles, CA 90024 USA. RP Goodson, JM (reprint author), Forsyth Inst, Dept Clin Res, 140 Fenway, Boston, MA 02115 USA. EM mgoodson@forsyth.org NR 24 TC 13 Z9 17 U1 1 U2 6 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 2007 VL 78 IS 8 BP 1568 EP 1579 DI 10.1902/jop.2007.060488 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 199JL UT WOS:000248691900014 PM 17668977 ER PT J AU Kim, DA Koszeghy, KL Badovinac, RL Kawai, T Hosokawa, I Howell, TH Karimbux, NY AF Kim, David A. Koszeghy, Kristian L. Badovinac, Rachel L. Kawai, Toshihisa Hosokawa, Ikuko Howell, T. Howard Karimbux, Nadeem Y. TI The effect of aspirin on gingival crevicular fluid levels of inflammatory and anti-inflammatory mediators in patients with gingivitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE aspirin; gingival crevicular fluid; gingivitis ID ALVEOLAR BONE LOSS; ADULT PERIODONTITIS; FLURBIPROFEN AB Background: Inflammatory and anti-inflammatory mediators may play a significant role in patients with gingivitis. The purpose of this study was to assess the short-term effects of the systemic administration of two different concentrations of aspirin (81 and 325 mg/day, by mouth) on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of 15-epi-lipoxin A(4) (15-epi-LXA(4)), lipoxin A(4), leukotriene B-4 (LTB4), prostaglandin E-2 (PGE(2)), and interleukin (IL)-6 and -1 beta in a sample of naturally occurring gingivitis patients. Methods: At day 0, after initial screening for entry, baseline periodontal parameters, including bleeding on probing (BOP), periodontal probing depths (PDs), and plaque index (PI) were measured, and GCF was sampled from 12 intrasulcular sites with filter paper strips for the measurement of six types of inflammatory and anti-inflammatory mediators using competitive enzyme immunoassay and enzyme-linked immunosorbent assay (prevalues). Forty-seven subjects were assigned randomly to one of three treatment groups: placebo (15 subjects); aspirin, 81 mg (16 subjects); and aspirin, 325 mg (16 subjects) once daily. On day 7, subjects were recalled for the measurement of periodontal parameters and collection of GCF samples for the measurement of six types of mediators (postvalues). Results: Changes in inflammatory and anti-inflammatory mediator levels were not statistically significant for any of the three treatment groups. However, when pre- and postvalues were compared in the subjects receiving aspirin, 325 mg, there was a negative trend in the relationship between 15-epi-LXA(4) and PGE(2), whereas the relationship between LTB4 and PGE(2) was not as strong. This might indicate that the subjects responding to aspirin-mediated PGE(2) Suppression effects produced higher 15-epi-LXA(4) in GCF than non-responders. No statistically significant differences in PD and PI between pre- and postvalues were found for any of the three treatment groups. However, the results demonstrated a significant increase in BOP when aspirin, 325 mg was compared to placebo (P < 0.001) and aspirin, 81 mg (P=0.001). Conclusions: Aspirin can have an affect on BOP in naturally occurring gingivitis patients. Although most of the inflammatory mediators did not show significantly detectable changes after aspirin treatment for 7 days, the trend of aspirin-associated increases of 15-epi-LXA(4) implied that this recently discovered aspirin-dependent eicosanoid may be associated with the increased incidence of BOP observed in the subjects who received aspirin therapy. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Kim, DA (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM dkim@hsdm.harvard.edu FU NIDCR NIH HHS [5 K08 DE016956-02] NR 17 TC 7 Z9 8 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 2007 VL 78 IS 8 BP 1620 EP 1626 DI 10.1902/jop.2007.070011 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 199JL UT WOS:000248691900019 PM 17668982 ER PT J AU Strack, S Millon, T AF Strack, Stephen Millon, Theodore TI Contributions to the dimensional assessment of personality disorders using million's model and the million clinical multiaxial inventory (MCMI-III) SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID EMPIRICAL-EVALUATION; CONVERGENT VALIDITY; SCALES; POLARITIES AB For over 35 years, Millions (1996) model of personality and the Millon Clinical Multiaxial Inventory (Millon, 1977, 1987, 2006) have been useful resources for clinicians to understand and assess personality disorders (PDs) and clinical syndromes in psychiatric patients. In this article, we highlight significant features of the model and test that have proved valuable to personologists in their quest for a more satisfactory taxonomy of PDs based on continuously distributed traits. We also describe Millon's (1996) prototypal domain approach to personality that combines dimensional and categorical elements for the description of PDs and their normal counterparts. C1 US Dept Vet Affairs, Ctr Ambulatory Care, Los Angeles, CA USA. Inst Adv Studies Personal & Psychopathol, Coral Gables, FL USA. RP Strack, S (reprint author), VA LAACC, Psychol Serv 116B, 351 E Temple St, Los Angeles, CA USA. EM snstrack@aol.com NR 64 TC 22 Z9 29 U1 0 U2 9 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD AUG PY 2007 VL 89 IS 1 BP 56 EP 69 PG 14 WC Psychology, Clinical; Psychology, Social SC Psychology GA 198BZ UT WOS:000248603300006 PM 17604534 ER PT J AU Yehuda, R Golier, JA Tischler, L Harvey, PD Newmark, R Yang, RK Buchsbaum, MS AF Yehuda, Rachel Golier, Julia A. Tischler, Lisa Harvey, Philip D. Newmark, Randall Yang, Ren Kui Buchsbaum, Monte S. TI Hippocampal volume in aging combat veterans with and without post-traumatic stress disorder: Relation to risk and resilience factors SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE hippocampus; memory performance; cortisol; glucocorticoid receptors; post-traumatic stress disorder; risk; resilience ID VEHICLE ACCIDENT VICTIMS; URINARY CORTISOL-LEVELS; CHILDHOOD SEXUAL-ABUSE; HOLOCAUST SURVIVORS; MEMORY PERFORMANCE; N-ACETYLASPARTATE; PYRAMIDAL NEURONS; GENE-EXPRESSION; PTSD SYMPTOMS; TRAUMA AB Objective: To examine whether there are post-traumatic stress disorder (PTSD) related differences in hippocampal volume in middle-aged and elderly veterans and to examine the relationship of neuroendocrine activity, memory performance, and measures of risk and resilience for PTSD to hippocampal volume in this cohort. Methods: Seventeen veterans with chronic PTSD and 16 veterans without chronic PTSD received an MRI scan followed by neuroendocrine assessment (24-h urinary cortisol excretion and the lysozyme IC(50-DEX), a measure of glucocorticoid receptor (GR) responsiveness), and cognitive testing. Results: Veterans with PTSD did not differ from those without PTSD in hippocampal volume, but they did show significantly lower urinary cortisol levels, and poorer memory performance on the Wechsler Logical Memory test and Digit Span test. Smaller left hippocampal volumes were observed in veterans who developed PTSD in response to their first reported traumatic exposure, compared to veterans who had first experienced a traumatic event to which they did not develop PTSD, prior to experiencing a subsequent event that led to PTSD. In contrast, the two neuroendocrine measures were associated with risk factors related to early trauma exposure. Conclusion: Although hippocampal volume was not found to differ between subjects with and without PTSD, smaller hippocampal volumes in PTSD may be associated with specific risk and resilience factors. These may be distinct from vulnerability markers associated with increased responsiveness to glucocorticoids and/or other neuroendocrine measures that have been observed in combat-related PTSD. Published by Elsevier Ltd. C1 Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, New York, NY USA. Bronx Vet Affairs Med Ctr, New York, NY USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, New York, NY USA. EM Rachel.Yehuda@med.va.gov FU NCRR NIH HHS [RR00071] NR 72 TC 47 Z9 49 U1 4 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD AUG PY 2007 VL 41 IS 5 BP 435 EP 445 DI 10.1016/j.jpsychires.2005.12.002 PG 11 WC Psychiatry SC Psychiatry GA 141MW UT WOS:000244583900008 PM 16445942 ER PT J AU Husain, MM Rush, AJ Trivedi, MH McClintock, SM Wisniewski, SR Davis, L Luther, JF Zisook, S Fava, M AF Husain, Mustafa M. Rush, A. John Trivedi, Madhukar H. McClintock, Shawn M. Wisniewski, Stephen R. Davis, Lori Luther, James F. Zisook, Sid Fava, Maurizio TI Pain in depression: STAR*D study findings SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE depression; pain; general medical comorbidities; depression subtypes ID QUALITY-OF-LIFE; SEQUENCED TREATMENT ALTERNATIVES; EPIDEMIOLOGIC CATCHMENT-AREA; PRIMARY-CARE PATIENTS; ILLNESS RATING-SCALE; REPORT QIDS-SR; MAJOR DEPRESSION; SOMATIC SYMPTOMS; QUICK INVENTORY; PSYCHOMETRIC EVALUATION AB Background: Pain complaints commonly accompany major depressive disorder (MDD). However, whether patients with MDD and pain complaints differ from those without pain complaints is not well studied. Objective: The objective of this study was to compare depressed outpatients with and those without current pain complaints in terms of sociodemographic, clinical, and presenting symptom features. Methods: The baseline clinical and sociodemographic data of a large representative outpatient sample with nonpsychotic MDD (n=3745) enrolled in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study were collected. Baseline information on pain complaints was based on Item No. 25 (somatic pain) of the 30-item Inventory of Depressive Symptornatology-Clinician Rating (IDS-C-30). Results: After adjusting for sex, depression severity (IDS-C-30 less Item No. 25), and general medical comorbidities (as measured by the Cumulative Illness Rating Scale total score), we found clinically meaningful differences between patients with and those without pain complaints. Younger, African American, Hispanic, and less educated patients were more likely to report pain complaints. In addition, those with pain complaints were more likely to report anxious features with irritable mood, sympathetic nervous system arousal, and gastrointestinal problems as well as poorer quality of life. Neither a more chronic course of illness nor suicidal ideation was associated with pain. Conclusions: Pain complaints are common among outpatients with MDD and are associated with certain symptom features and poorer quality of life. However, the findings of this study suggest that depression accompanied by pain complaints does not increase the clinical psychiatric burden or chronicity of depression. (c) 2007 Published by Elsevier Inc. C1 Univ Texas, Dept Psychiat, SW Med Ctr, Dallas, TX 75390 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Vet Affairs Med Ctr, Tuscaloosa, AL USA. Univ Alabama, Birmingham, AL USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Husain, MM (reprint author), Univ Texas, Dept Psychiat, SW Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM mustafa.husain@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 73 TC 45 Z9 48 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD AUG PY 2007 VL 63 IS 2 BP 113 EP 122 DI 10.1016/j.jpsychores.2007.02.009 PG 10 WC Psychiatry SC Psychiatry GA 198RD UT WOS:000248644300002 PM 17662746 ER PT J AU Marc, LG Testa, MA Walker, AM Robbins, GK Shafer, RW Anderson, NB Berkman, LF AF Marc, Linda G. Testa, Marcia A. Walker, Alexander M. Robbins, Gregroy K. Shafer, Robert W. Anderson, Norman B. Berkman, Lisa F. CA ACTG Data Anal Concept Sheet Study TI Educational attainment and response to HAART during initial therapy for HIV-1 infection SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Review DE adherence self-efficacy; antiretroviral; educational attainment; HIV/AIDS; socioeconomic status; regimen failure ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRESSFUL LIFE EVENTS; ACTIVE ANTIRETROVIRAL THERAPY; SEQUENTIAL 3-DRUG REGIMENS; SOCIOECONOMIC-STATUS; CLINICAL-TRIALS; SOCIAL-CLASS; DEPRESSIVE SYMPTOMS; GAY MEN; RESPIRATORY-INFECTIONS AB Objective: Previous research has demonstrated an association between educational attainment (EA) and negative physical and psychological outcomes. This study investigated whether EA is associated with regimen failure during initial therapy with highly active antiretroviral treatment (HAART) and whether adherence self-efficacy (ASE), a coping resource, moderates the relationship between EA and regimen failure. Methods: A secondary analysis of AIDS Clinical Trial Group Protocol 384, an international, multicenter, randomized, partially double-blinded trial, included 799 male and 181 female antiretroviral-naive subjects (age, 37.0 +/- 9.5 years). Participants were recruited from 1998 to 1999 and followed for a median of 2.3 years across 81 centers. The dependent variable was "time to first regimen failure." Covariates include baseline HIV-1 log(10) RNA and CD4(+) counts, self-reported adherence, study site, ASE, age, sex, race, treatment assignment, and baseline use of nonantiretroviral medications. Results: ASE significantly moderated the relationship between EA and regimen failure. Results showed that for every 10-unit increase in ASE, individuals with "less than high school" education had a 17% reduction in regimen failure (hazard ratio=0.83; 95% confidence interval=0.70-0.98) when compared to the reference group "college/graduate," even after adjusting for baseline factors known to contribute to regimen failure. The time to first regimen failure was shorter with decreasing EA, trending toward significance (P=.08). Conclusions: There is a social gradient in HAART effectiveness, and ASE reduces the deleterious effects of lower EA on regimen failure. We recommend designing controlled interventions to evaluate the effectiveness of programs that increase ASE prior to initiation with HAART, particularly for those with lower EA. (c) 2007 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Psychiat, White Plains, NY 10605 USA. Cornell HIV Clin Trials Unit, New York, NY USA. Harvard Sch Publ Hlth, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Amer Psychiat Assoc, Washington, DC USA. RP Marc, LG (reprint author), Cornell Univ, Weill Med Coll, Dept Psychiat, 21 Bloomingdale Rd,Unit 2 S, White Plains, NY 10605 USA. EM linda.marc@post.harvard.edu RI Robbins, Gregory/F-7988-2011 FU NIAID NIH HHS [AI25868, AI-69419, AI25924, AI27659, AI38858]; NIMH NIH HHS [MH19132] NR 104 TC 13 Z9 14 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD AUG PY 2007 VL 63 IS 2 BP 207 EP 216 DI 10.1016/j.jpsychores.2007.04.009 PG 10 WC Psychiatry SC Psychiatry GA 198RD UT WOS:000248644300015 PM 17662759 ER PT J AU Schumacher, HR AF Schumacher, H. Ralph, Jr. TI Adel G. Fam MD, FRCPC, MACR October 14, 1936-April 16, 2007 - In tribute SO JOURNAL OF RHEUMATOLOGY LA English DT Biographical-Item C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Univ Penn, Sch Med, Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2007 VL 34 IS 8 BP 1782 EP 1782 PG 1 WC Rheumatology SC Rheumatology GA 200AL UT WOS:000248736200027 ER PT J AU Eberwein, CA Pratt, SR McNeil, MR Fossett, TRD Szuminsky, NJ Doyle, PJ AF Eberwein, Cynthia A. Pratt, Sheila R. McNeil, Malcolm R. Fossett, Tepanta R. D. Szuminsky, Neil J. Doyle, Patrick J. TI Auditory performance characteristics of the computerized revised token test (CRTT) SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE language comprehension; auditory processing; auditory comprehension; auditory processing disorder ID SPEECH-RECOGNITION PERFORMANCE; FREQUENCY COMPRESSION; ELDERLY LISTENERS; WORD-RECOGNITION; COMPREHENSION; HEARING; CHILDREN; TIME; INTELLIGIBILITY; ADULTS AB Purpose: To assess the Computerized Revised Token Test (CRTT) performance of individuals with normal hearing under several intensity conditions and under several spectral and temporal perturbation conditions. Method: Sixty normal-hearing listeners were randomly assigned to 1 of 3 groups. Group 1 provided performance-intensity information about CRTT performance using uncompressed acoustic stimuli. Groups 2 and 3 completed the CRTT using temporally and spectrally compressed and expanded stimuli. CRTT performance functions were plotted for each group. Results: Group 1 required minimal audibility to perform maximally on this task. As expected, Groups 2 and 3 showed significant differences across subtests, regardless of distortion condition. Mean differences in performance between successive conditions for Group 2 increased beyond 40% time compressed. There was 1 significant difference for the time-expanded condition. There were no differences across frequency compressed and expanded conditions. Conclusion: Young listeners require limited signal gain on the CRTT to achieve maximum performance. Time and frequency compression and expansion results were consistent with previous findings with varying types of speech stimuli. The results have implications for administration and interpretation of the CRTT administered to persons from other populations and will help in the development of a normative database for the CRTT. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. Necess Consulting, Mars, PA USA. RP Eberwein, CA (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. RI Pratt, Sheila/H-7139-2013 NR 46 TC 2 Z9 2 U1 0 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD AUG PY 2007 VL 50 IS 4 BP 865 EP 877 DI 10.1044/1092-4388(2007/061) PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 200AQ UT WOS:000248736700006 PM 17675592 ER PT J AU Goss, P von Eichel, L AF Goss, Paul von Eichel, Leonie TI Summary of aromatase inhibitor trials: The past and future SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE aromatase inhibitors; adjuvant endocrine; endocrine resistance ID EARLY BREAST-CANCER; DELAYED ADJUVANT TAMOXIFEN; POSTMENOPAUSAL WOMEN; MEGESTROL-ACETATE; RANDOMIZED-TRIAL; DOUBLE-BLIND; ESTROGEN-RECEPTOR; PHASE-III; ANASTROZOLE ARIMIDEX; OVARIECTOMIZED RATS AB Antagonizing estrogen by inhibition of aromatase has become a mainstay of adjuvant endocrine therapy in women with hormone receptor positive (ER+) breast cancer. Recent trials have shown an incremental gain for the AIs over tamoxifen when given as an up-front alternative to tamoxifen, but additionally added benefit is achieved by giving them in sequence with tamoxifen after either an early switch (2-3 years) or as a late switch (5 years). The true clinical implications of accelerated bone resorption from AIs is becoming better understood and its management defined. AI minimally effect quality of life. The chronic relapsing nature of ER+ breast cancer implies long term therapy will be of benefit in selected patients. Outstanding issues under investigation include optimal duration of endocrine therapy, optimal sequence, optimal agents and whether combining anti-estrogens will yield advantage. The role of AIs is also under investigation in premenopausal women in combination with ovarian function suppression. Identifying prognostic and predictive factors of endocrine therapy is important as is the identification and overcoming of resistance mechanisms. Both tumor and host signatures are being pursued to this end. Optimizing, expanding and extending endocrine therapy is likely to add further to patient outcome. (C) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Klinikum Hamburg Eppendorf, Hamburg, Germany. RP Goss, P (reprint author), Massachusetts Gen Hosp, Ctr Canc, LRH 302,55 Fruit St, Boston, MA 02114 USA. EM pgoss@partners.org NR 57 TC 7 Z9 8 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD AUG-SEP PY 2007 VL 106 IS 1-5 SI SI BP 40 EP 48 DI 10.1016/j.jsbmb.2007.05.023 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 219IO UT WOS:000250078300007 PM 17627816 ER PT J AU Krasner, C AF Krasner, Carolyn TI Aromatase inhibitors in gynecologic cancers SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Aromatase Conference CY SEP 18-20, 2006 CL Baltimore, MD DE aromatase inhibitors; gynecologic cancer ID ENDOMETRIAL STROMAL SARCOMA; PHASE-II TRIAL; EPITHELIAL OVARIAN-CANCER; ONCOLOGY-GROUP; HORMONAL-THERAPY; MEDROXYPROGESTERONE ACETATE; STEROID-RECEPTORS; LUNG-CANCER; CARCINOMA; RECURRENT AB The female genital tract is hormonally responsive, and consequently some tumors, which arise within in it, may be treated at least in part, with hormonal manipulation. The range of responses in clinical trials and case reports will be reviewed. Many of these diseases are too rare for clinical trial testing, and in some cases evidence is anecdotal at best. Recurrences of ovarian cancer have been treated with tamoxifen and megesterol acetate with variable response rates from 0 to 56%. The favorable toxicity profile of aromatase inhibitors led to trials of these agents for the treatment of relapsed epithelial ovarian cancer. These agents have proved tolerable with minor response rates but a significant disease stabilization rate, which may be prolonged in a minority of cases. It is unclear if these responses may be predicted by estrogen receptor expression or aromatase expression. Anastrazole has also been tried in combination with an EGFR receptor-inhibitor, again showing minor responses but possibly an increase in TTT in some patients. Granulosa cell tumors of the ovary are rare, hormonally sensitive tumors, with reported responses to a variety of hormonal manipulations, including aromatase inhibition. In addition, combined endocrine blockade, including aromatase inhibition, has been tried with reports of success. Endometrial cancers, particularly type I lesions, are often treated with hormonal manipulation, most commonly with progestins, but also with antiestrogens such as tamoxifen. A trial of aromatase inhibition in the treatment of recurrent endometrial cancer showed minimal responses. Endometrial stromal sarcoma, an uncommon uterine malignancy, has shown response to hormonal treatments, with multiple case reports of efficacy of aromatase inhibition. Despite the rarity of some of these tumor types, rare tumor study groups, such as within the Gynecologic Oncology Group, should make an effort to prospectively define the utility of these treatments. (C) 2007 Published by Elsevier Ltd. C1 Massachusetts Gen Hosp, Gillette Ctr Womens Oncol, Boston, MA 02114 USA. RP Krasner, C (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Oncol, Boston, MA 02114 USA. NR 28 TC 23 Z9 25 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD AUG-SEP PY 2007 VL 106 IS 1-5 SI SI BP 76 EP 80 DI 10.1016/j.jsbmb.2007.05.026 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 219IO UT WOS:000250078300012 PM 17826626 ER PT J AU Leder, BZ AF Leder, Benjamin Z. TI Testosterone, estradiol and aromatase inhibitor therapy in elderly men SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Aromatase Conference CY SEP 18-20, 2006 CL Baltimore, MD DE aromatase therapy in elderly men ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; ENDOGENOUS SEX-HORMONES; DENSITY-LIPOPROTEIN CHOLESTEROL; PLASMA TOTAL TESTOSTERONE; HEALTH INITIATIVE MEMORY; ISCHEMIC-HEART-DISEASE; OSTEOBLAST-LIKE CELLS; C-REACTIVE PROTEIN; ADULT MALE-MICE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM bzleder@partners.org NR 94 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD AUG-SEP PY 2007 VL 106 IS 1-5 SI SI BP 162 EP 167 DI 10.1016/j.jsbmb.2007.05.018 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 219IO UT WOS:000250078300023 PM 17600698 ER PT J AU Songer, JE Rosowski, JJ AF Songer, Jocelyn E. Rosowski, John J. TI Transmission matrix analysis of the chinchilla middle ear SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID INPUT IMPEDANCE; CAT; MODEL; ADMITTANCE; DEPENDENCE; RESPONSES; COCHLEA; MOTION AB Despite the common use of the chinchilla as an animal model in auditory research, a complete characterization of the chinchilla middle ear using transmission matrix analysis has not been performed. In this paper we describe measurements of middle-ear input admittance and stapes velocity in ears with the middle-ear cavity opened under three conditions: intact tympano-ossicular system and cochlea, after the cochlea has been drained, and after the stapes has been fixed. These measurements, made with stimulus frequencies of 100-8000 Hz, are used to define the transmission matrix parameters of the middle ear and to calculate the cochlear input impedance as well as the middle-ear output impedance. This transmission characterization of the chinchilla middle ear will be useful for modeling auditory sensitivity in the normal and pathological chinchilla ear. (c) 2007 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, MIT, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Songer, JE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM jocelyns@paradoxical.net FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-24] NR 36 TC 19 Z9 19 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 2007 VL 122 IS 2 BP 932 EP 942 DI 10.1121/1.2747157 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 198RB UT WOS:000248644100023 PM 17672642 ER PT J AU Songer, JE Rosowski, JJ AF Songer, Jocelyn E. Rosowski, John J. TI A mechano-acoustic model of the effect of superior canal dehiscence on hearing in chinchilla SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MIDDLE-EAR; VERTIGO; ADMITTANCE AB Superior canal dehiscence (SCD) is a pathological condition of the ear that can cause a conductive hearing loss. The effect of SCD (a hole in the bony wall of the superior semicircular canal) on chinchilla middle- and inner-ear mechanics is analyzed with a circuit model of the dehiscence. The model is used to predict the effect of dehiscence on auditory sensitivity and mechanics. These predictions are compared to previously published measurements of dehiscence related changes in chinchilla cochlear potential, middle-ear input admittance and stapes velocity. The comparisons show that the model predictions are both qualitatively and quantitatively similar to the physiological results for frequencies where physiologic data are available. The similarity supports the third-window hypothesis of the effect of superior canal dehiscence on auditory sensitivity and mechanics and provides the groundwork for the development of a model that predicts the effect of superior canal dehiscence syndrome on auditory sensitivity and mechanics in humans. (c) 2007 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, MIT, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Songer, JE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM jocelyns@paradoxical.net FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-24] NR 14 TC 34 Z9 34 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 2007 VL 122 IS 2 BP 943 EP 951 DI 10.1121/1.2747158 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 198RB UT WOS:000248644100024 PM 17672643 ER PT J AU Born, CT Briggs, SM Ciraulo, DL Frykberg, ER Hammond, JS Hirshberg, A Lhowe, DW O'Neill, PA Mead, J AF Born, Christopher T. Briggs, Susan M. Ciraulo, David L. Frykberg, Eric R. Hammond, Jeffrey S. Hirshberg, Asher Lhowe, David W. O'Neill, Patricia A. Mead, Joann TI Disasters and mass casualties: II. Explosive, biologic, chemical, and nuclear agents SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID PRIMARY BLAST INJURY; CIVILIAN TERRORISM; MANAGEMENT; BIOTERRORISM; OVERPRESSURE; PRINCIPLES; MISSILES; BOMBINGS; EXPOSURE; SURGEON AB Terrorists' use of explosive, biologic, chemical, and nuclear agents constitutes the potential for catastrophic events. Understanding the unique aspects of these agents can help in preparing for such disasters with the intent of mitigating injury and loss of life. Explosive agents continue to be the most common weapons of terrorists and the most prevalent cause of injuries and fatalities. Knowledge of blast pathomechanics and patterns of injury allows for improved diagnostic and treatment strategies. A practical understanding of potential biologic, chemical, and nuclear agents, their attendant clinical symptoms, and recommended management strategies is an important prerequisite for optimal preparation and response to these less frequently used agents of mass casualty. Orthopaedic surgeons should be aware of the principles of management of catastrophic events. Stress is less an issue when one is adequately prepared. Decontamination is essential both to manage victims and prevent further spread of toxic agents to first responders and medical personnel. It is important to assess the risk of potential threats, thereby allowing disaster planning and preparation to be proportional and aligned with the actual casualty event. C1 Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Rhode Isl Hosp, Orthopaed Trauma Serv, Providence, RI USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Maine Med Ctr, Portland, ME 04102 USA. RP Born, CT (reprint author), Univ Orthopaed, Suite 200,2 Dudley St, Providence, RI 02905 USA. NR 72 TC 12 Z9 12 U1 2 U2 5 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD AUG PY 2007 VL 15 IS 8 BP 461 EP 473 PG 13 WC Orthopedics SC Orthopedics GA 198QG UT WOS:000248642000003 PM 17664366 ER PT J AU Wylie-Rosett, J Albright, AA Apovian, C Clark, NG Delahanty, L Franz, MJ Hoogwerf, B Kulkarni, K Lichtenstein, AH Mayer-Davis, E Mooradian, AD Wheeler, M AF Wylie-Rosett, Judith Albright, Ann A. Apovian, Caroline Clark, Nathaniel G. Delahanty, Linda Franz, Marion J. Hoogwerf, Byron Kulkarni, Karmeen Lichtenstein, Alice H. Mayer-Davis, Elizabeth Mooradian, Arshag D. Wheeler, Madelyn TI 2006-2007 American Diabetes Association nutrition recommendations: Issues for practice translation SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID INSULIN-RESISTANCE ATHEROSCLEROSIS; CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; LOW-CARBOHYDRATE DIET; GLYCEMIC INDEX; WEIGHT-LOSS; RANDOMIZED-TRIAL; BARIATRIC SURGERY; OBESE ADULTS C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Ctr Dis Control, Div Diabet Translat, Atlanta, GA USA. Univ Calif San Francisco, Dept Hlth Serv, Calif Diabet Program, San Francisco, CA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Novo Nordisk Inc, Diabet Clin Res & Med Affairs, Princeton, NJ USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Nutr Concepts Franz Inc, Minneapolis, MN USA. Cleveland Clin, Dept Diabet Endocrinol & Metab, Cleveland, OH 44106 USA. Abbott Diabet Care, Sci Affairs, Alameda, CA USA. Jean Mayer USDA Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC USA. Univ Florida, Coll Med, Dept Med, Jacksonville, FL USA. Nutr Comp Concepts, Res Nutr, Zionville, IN USA. RP Wylie-Rosett, J (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jwrosett@aecom.yu.edu OI Apovian, Caroline/0000-0002-8029-1922 NR 45 TC 16 Z9 16 U1 0 U2 4 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 2007 VL 107 IS 8 BP 1296 EP 1304 DI 10.1016/j.jada.2007.05.009 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 197TE UT WOS:000248578600007 PM 17659893 ER PT J AU Li, G Rhew, IC Shofer, JB Kukull, WA Breitner, JCS Peskind, E Bowen, JD McCormick, W Teri, L Crane, PK Larson, EB AF Li, Ge Rhew, Isaac C. Shofer, Jane B. Kukull, Walter A. Breitner, John C. S. Peskind, Elaine Bowen, James D. McCormick, Wayne Teri, Linda Crane, Paul K. Larson, Eric B. TI Age-varying association between blood pressure and risk of dementia in those aged 65 and older: A community-based prospective cohort study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE blood pressure; hypertension; dementia; Alzheimer's disease ID WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; COGNITIVE DECLINE; FOLLOW-UP; APOLIPOPROTEIN-E; HYPOPERFUSION; INDIVIDUALS; PREVALENCE; ROTTERDAM AB Objectives: To assess variation in the association between blood pressure (BP) and risk for dementia across a spectrum of older ages and to examine BP changes before dementia onset. Design: Prospective cohort study. Setting: A large health maintenance organization in Seattle, Washington. Participants: A cohort of 2,356 members of a large health maintenance organization aged 65 and older who were initially without dementia. Measurements: Dementia diagnosis was assessed biennially, and systolic (SBP) and diastolic BP (DBP) were measured at baseline and at four follow-up assessments. Cox proportional hazards models were used to estimate hazard ratios (HRs) for dementia and Alzheimer's disease (AD) associated with baseline BP in different age groups. Results: Within the youngest age group (65-74 at enrollment) a greater risk for dementia was found in participants with high SBP (>= 160 mmHg) (hazard ratio (HR) = 1.60, 95% confidence interval (CI) = 1.01-2.55) or borderline-high DBP (80-89 mmHg) (HR = 1.59, 95% CI = 1.07-2.35) than for those with normal BP (SBP < 140 mmHg and DBP < 80 mmHg). The dementia risk associated with SBP declined with increasing age (SBP-by-age interaction, P = .01). SBP declined similarly with aging in subjects who developed dementia and those who did not. Thus, in this sample, the association between SBP and dementia risk was not dependent on when BP was measured in relation to onset of dementia. Conclusion: High SBP was associated with greater risk of dementia in the young elderly (< 75) but not in older subjects. Adequate control of hypertension in early old age may reduce the risk for dementia. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, Seattle, WA 98108 USA. 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 Med, Seattle, WA 98195 USA. Univ Washington, Dept psychosocial & Community Hlth, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98121 USA. RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way,S-116,6 East, Seattle, WA 98108 USA. EM gli@u.washington.edu RI Crane, Paul/C-8623-2014; OI Kukull, Walter/0000-0001-8761-9014; Crane, Paul/0000-0003-4278-7465 FU NIA NIH HHS [AG06781, AG20020] NR 43 TC 50 Z9 52 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2007 VL 55 IS 8 BP 1161 EP 1167 DI 10.1111/j.1532-5415.2007.01233.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 197HE UT WOS:000248544400001 PM 17661953 ER PT J AU Bates-Jensen, BM McCreath, HE Kono, A Apeles, NCR Alessi, C AF Bates-Jensen, Barbara M. McCreath, Heatber E. Kono, Ayuml Apeles, Neil Christopher R. Alessi, Cathy TI Subepidermal moisture predicts erythema and stage 1 pressure ulcers in nursing home residents: A pilot study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE erythema; Stage 1 pressure ulcers; moisture ID BRADEN SCALE; SORE RISK; SKIN; MULTISITE; CARE AB Objectives: To examine the relationship between a measure of subepidermal moisture (SEM) and visual skin assessment (VSA) of erythema and Stage 1 pressure ulcers (PUs) performed a week later in nursing home (NH) residents. Design: Descriptive, cohort study. Setting: Two NHs. Participants: Thirty-five residents. Methods: Concurrent VSAs and SEM readings were obtained at the sacrum, right and left trochanters, buttocks, and ischial tuberosities weekly for 52 weeks. SEM was measured using a handheld dermal phase meter, with higher readings indicating greater SEM (range 0-999 dermal phase units [DPUs]). VSA was rated as normal, erythema/Stage 1 PU, or Stage 2+PU. SEM was modeled as a predictor of VSA of erythema and PUs 1 week later (controlling for clustering), with concurrent moisture, Braden Scale PU risk status, anatomic site, and ethnicity as covariates. Results: Participants had a mean age of 84.7, 83% were female, and 80% were non-Hispanic white. SEM measures were lowest for normal skin (97 +/- 122 DPU), higher for erythema/Stage 1 PUs (192 188 DPU), and highest for Stage 2+PUs (569 +/- 320 DPU) across all sites (all P<.001). SEM was responsive to changes in VSA, and higher SEM predicted greater likelihood of erythema/Stage 1 PU the next week (odds ratio = 1.26 for every 100-DPU increase in SEM, P =.04). Conclusion: SEM measures are associated with concurrent erythema and PUs and future (1 week later) development of erythema/Stage 1 PUs. SEM may assist in predicting early PU damage, allowing for earlier intervention to prevent skin damage. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Osaka City Univ, Osaka 558, Japan. Valley Presbyterian Hosp, Van Nuys, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sch Nursing, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, 16111 Plummer St,11E, Sepulveda, CA 91343 USA. EM bbatesjensen@sonnet.ucla.edu NR 32 TC 16 Z9 16 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2007 VL 55 IS 8 BP 1199 EP 1205 DI 10.1111/j.1532-5415.2007.01261.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 197HE UT WOS:000248544400006 PM 17661958 ER PT J AU Chodosh, J Mittman, BS Connor, KI Vassar, SD Lee, ML DeMonte, RW Ganiats, TG Heikoff, LE Rubenstein, LZ Della Penna, RD Vickrey, BG AF Chodosh, Joshua Mittman, Brian S. Connor, Karen I. Vassar, Stefanie D. Lee, Martin L. DeMonte, Robert W. Ganiats, Theodore G. Heikoff, Lisa E. Rubenstein, Laurence Z. Della Penna, Richard D. Vickrey, Barbara G. TI Caring for patients with dementia: How good is the quality of care? results from three health systems SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; quality of care; comorbidity; caregiver ID MANAGING ALZHEIMERS-DISEASE; RANDOMIZED CONTROLLED-TRIAL; OLDER PATIENTS; DEPRESSION; GUIDELINES; OUTCOMES; WELL; ASSOCIATION; POPULATION; VALIDATION AB Objectives: To describe the quality of dementia care within one U.S. metropolitan area and to investigate associations between variations in quality and patient, caregiver, and health system characteristics. Design: Observational, cross-sectional. Setting and Participants: Three hundred eighty-seven patient-caregiver pairs from three healthcare organizations Measurements: Using caregiver surveys and medical record abstraction to assess 18 dementia care processes drawn from existing guidelines, the proportion adherent to each care process was calculated, as well as mean percentages of adherence aggregated within four care dimensions: assessment (6 processes), treatment (6 processes), education and support (3 processes), and safety (3 processes). For each dimension, associations between adherence and patient, caregiver, and health system characteristics were investigated using multivariable models. Results: Adherence ranged from 9% to 79% for the 18 individual care processes; 11 processes had less than 40% adherence. Mean percentage adherence across the four care dimensions was 37% for assessment, 33% for treatment, 52% for education and support, and 21% for safety. Higher comorbidity was associated with greater adherence across all four dimensions, whereas greater caregiver knowledge (in particular, one item) was associated with higher care quality in three of four care dimensions. For selected dimensions, greater adherence was also associated with greater dementia severity and with more geriatrics or neurologist visits. Conclusion: In general, dementia care quality has considerable room for improvement. Although greater comorbidity and dementia severity were associated with better quality, caregiver knowledge was the most consistent caregiver characteristic associated with better adherence. These findings offer opportunities for targeting low quality and suggest potential focused interventions. C1 GRECC, Dept Vet Affairs, Los Angeles, CA 90073 USA. Greater Los Angeles Hlth Serv Res & Dev Serv Ctr, Dept Vet Affairs, Sepulveda, CA USA. Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Scripps Clin, San Diego, CA 92103 USA. Kaiser Permanente Med Ctr, San Diego, CA USA. Permanente Federation, Care Management Inst, Oakland, CA USA. RP Chodosh, J (reprint author), GRECC, Dept Vet Affairs, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jChodosh@mednet.ucla.edu OI Mittman, Brian/0000-0003-3589-9178; Penna, Maria Pietronilla/0000-0002-0982-3893; Chodosh, Joshua/0000-0001-7784-4306 NR 43 TC 37 Z9 37 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2007 VL 55 IS 8 BP 1260 EP 1268 DI 10.1111/j.1532-5415.2007.01249.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 197HE UT WOS:000248544400015 PM 17661967 ER PT J AU Dodd, JD Aquino, SL Sharma, A AF Dodd, Jonathan D. Aquino, Suzanne L. Sharma, Amita TI Babesiosis: CT and hematologic findings SO JOURNAL OF THORACIC IMAGING LA English DT Article DE babesiosis/diagnosis; computed tomography; humans ID RESPIRATORY-DISTRESS-SYNDROME AB Babesiosis is a tick-borne illness caused by the protozoan Bahesia microti. Most patients are asymptomatic but the infection may produce a spectrum of symptoms in immunocomprimised patients, especially asplenic patients. These range from mild lever, sweats, fatigue, and myalgias to severe multiorgan failure, including acute respiratory distress syndrome and death. Radiographic appearances include bilateral patchy air space and interstitial opacities. We report the radiographic, high-resolution computed tomography (HRCT), and hematologic appearances in a 63-year-old man presenting with acute babesisois. HRCT images revealed smooth septal thickening and intralobular lines superimposed on ground glass opacities in both upper lobes. Follow-up HRCT after 2 weeks of therapy demonstrated resolution of the pulmonary parenchymal abnormalities. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Dodd, JD (reprint author), St Vincents Univ Hosp, Dept Radiol, Elm Pk, Dublin 4, Ireland. EM jonniedodd@gmail.com 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 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD AUG PY 2007 VL 22 IS 3 BP 271 EP 273 DI 10.1097/RTI.0b013e3180546823 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 205WG UT WOS:000249144700013 PM 17721341 ER PT J AU Preis, O Digumarthy, SR Wright, CD Shepard, JAO AF Preis, Ori Digumarthy, Subba Rao Wright, Cameron Dorrans Shepard, Jo-Anne O'Malley TI Atrioesophageal fistula after catheter pulmonary venous ablation for atrial fibrillation: Imaging features SO JOURNAL OF THORACIC IMAGING LA English DT Editorial Material DE atrioesophageal fistula; pulmonary vein ablation; atrial fibrillation ID RADIOFREQUENCY ABLATION; ESOPHAGUS; ANATOMY AB Atrioesophageal fistula is a rare but highly morbid complication of catheter-mediated pulmonary vein ablation for the treatment of atrial fibrillation. Among patients who do not exsanguinate from upper gastrointestinal tract bleeding, presentation includes sepsis and embolic cerebrovascular disease. We present a case of atrioesophageal fistula after pulmonary venous ablation as a treatment for atrial fibrillation, focusing on the imaging features of this diagnosis. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. RP Preis, O (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Founders 216, Boston, MA 02114 USA. EM opreis@partners.org NR 11 TC 13 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD AUG PY 2007 VL 22 IS 3 BP 283 EP 285 DI 10.1097/RTI.0b013e318054e26f PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 205WG UT WOS:000249144700017 PM 17721345 ER PT J AU Eberhardt, WE Korfee, S Johnson, BE Herbst, RS Natale, RB Kennedy, SJ Langmuir, P AF Eberhardt, Wilfried E. Korfee, Soenke Johnson, Bruce E. Herbst, Roy S. Natale, Ronald B. Kennedy, Sarah J. Langmuir, Peter TI Vandetanib in advanced NSCLC: an ongoing clinical evaluation program SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Hosp Duisburg Essen, Dept Internal Med Canc Res, W German Canc Ctr, Essen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. AstraZeneca, Wilmington, DE USA. 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S467 EP S468 DI 10.1097/01.JTO.0000283414.23120.66 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600498 ER PT J AU Engelman, JA Zejnullahu, K Mitsudomi, T Hyland, C Park, JO Lindeman, N Gale, CM Zhao, XJ Christensen, J Rogers, RM Cappuzzo, F Mok, T Lee, C Bruce, JE Cantley, LC Janne, PA AF Engelman, Jeffrey A. Zejnullahu, Kreshnik Mitsudomi, Tetsuya Hyland, Courtney Park, Joon Oh Lindeman, Neal Gale, Christopher-Michael Zhao Xiaojun Christensen, James Rogers, Rogers M. Cappuzzo, Federico Mok, Tony Lee, Charles Bruce, Johnson E. Cantley, Lewis C. Janne, Pasi A. TI Mechanisms of activating PI3K signaling in lung cancers that become resistant EGFR tyrosine kinase inhibitors SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S396 EP S396 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600349 ER PT J AU Herth, FJ Eberhardt, R Muley, T Krasnik, M Ernst, A AF Herth, Felix J. Eberhardt, Ralf Muley, Thomas Krasnik, Mark Ernst, Armin TI Resistance index through EBUS in enlarged mediastinal lymph nodes - a new technique to evaluate for malignant involvement SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Thoraxklin Heidelberg, Heidelberg, Germany. Dept Thorac Surg, Copenhagen, Denmark. Harvard Univ, Sch Med, BIDMC, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S417 EP S417 DI 10.1097/01.JTO.0000283307.17690.23 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600393 ER PT J AU Herth, FJ Ernst, A Yasufuku, K Annema, J Rintoul, R Krasnik, M AF Herth, Felix J. Ernst, Armin Yasufuku, Kazu Annema, Jouke Rintoul, Robert Krasnik, Mark TI Endobronchial ultrasound with transbronchial needle aspiration for restaging the mediastinum SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Thoraxklin Heidelberg, Heidelberg, Germany. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Chiba Univ, Dept Thorac Surg, Chiba, Japan. Leiden Univ, Leiden, Netherlands. Papworth Hosp, Cambridge CB3 8RE, England. Depp Thoraqc Surg, Copenhagen, Denmark. RI Rintoul, Robert/Q-1727-2015 OI Rintoul, Robert/0000-0003-3875-3780 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S361 EP S362 DI 10.1097/01.JTO.0000283195.56577.b6 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600281 ER PT J AU Jackman, DM Gallegos, RM Giaccone, G Janne, PA Johnson, BE AF Jackman, David M. Gallegos, Ruiz Marielle Giaccone, Giuseppe Janne, Pasi A. Johnson, Bruce E. TI The impact of EGFR and KRAS genotype in chemotherapy-naive patients with advanced non-small cell lung cancer treated with erlotinib SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Natl Canc Inst, Washington, DC 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S395 EP S396 DI 10.1097/01.JTO.0000283262.38218.78 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600348 ER PT J AU Johnson, BE Paz-Ares, L De Brand, F Sebastian, M Stewart, DJ Eberhardt, W Krebs, A Langmuir, P Herbst, RS Heymach, JV AF Johnson, Bruce E. Paz-Ares, Luis De Brand, Filippo Sebastian, Martin Stewart, David J. Eberhardt, Wilfried Krebs, Annetta Langmuir, Peter Herbst, Roy S. Heymach, John, V TI Randomized Phase II study of vandetanib alone or in combination with carboplatin and paclitaxel as 1st-line treatment for advanced NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Doce Octubre Univ Hosp, Madrid, Spain. European Inst Oncol, Milan, Italy. Univ Mainz, Med Klin 3, D-6500 Mainz, Germany. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Duisburg Essen, Univ Klinikum, Essen, Germany. AstraZeneca, Wilmington, DE USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S358 EP S359 DI 10.1097/01.JTO.0000283189.62415.3d PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600275 ER PT J AU Johnson, BE AF Johnson, Bruce E. TI Impact of genomic changes on the treatment of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S276 EP S276 DI 10.1097/01.JTO.0000283051.73085.9d PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600137 ER PT J AU Keith, RL Jackson, MK Meisinger, V Miller, YE Franklin, WA Hirsch, F Kittelson, J Merrick, D Kelly, K Bunn, PA AF Keith, Robert L. Jackson, Mary K. Meisinger, Vicki Miller, York E. Franklin, Wilbur A. Hirsch, Fred Kittelson, John Merrick, Daniel Kelly, Karen Bunn, Paul A. TI Update on the use of oral iloprost for the chemoprevention of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 UCDHSC, Denver VA Med Ctr, Denver, CO USA. Colorado SPORE Lung Canc, Denver, CO USA. Univ Kansas, Kansas City, KS 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S330 EP S331 DI 10.1097/01.JTO.0000283135.30305.c8 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600221 ER PT J AU Koivunen, JP Kim, J Lee, J Meyerson, ML Kwok-Kin, W Richards, WG Sugarbaker, DJ Johnson, BE Janne, PA AF Koivunen, Jussi P. Kim, Jhingook Lee, Jinseon Meyerson, Matthew L. Kwok-Kin, Wong Richards, William G. Sugarbaker, David J. Johnson, Bruce E. Janne, Pasi A. TI Mutations in the LKB1 tumor suppressor are frequently found in tumors from Caucasian NSCLC patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S378 EP S379 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600315 ER PT J AU Lynch, TJ Patel, T Dreisbach, L McCleod, M Heim, WJ Robert, H Eugene, P Virginie, P Weber, MR Woytowitz, D AF Lynch, Thomas J. Patel, Taral Dreisbach, Luke McCleod, Michael Heim, William J. Robert, Hermann Eugene, Paschold Virginie, Pautret Weber, Martin R. Woytowitz, David TI A randomized multicenter phase III study of cetuximab (Erbitux((R))) in combination with taxane/carboplatin versus taxane/carboplatin alone as first-line treatment for patients with advanced/metastatic non-small cell lung cancer (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mid Ohio Oncol Hematol Inc, Columbus, OH USA. Desert Hematol & Oncol Med Grp, Rancho Mirage, CA USA. Florida Canc Specialists, Ft Myers, FL USA. Assoc NE, Hematol & Oncol, Dunmore, PA USA. Wellstar Canc Res Off, Marietta, GA USA. Piedmont Hematol Oncol Assoc, Winston Salem, NC USA. Bristol Myers Squibb Co, Braine lAlleud, Belgium. Bristol Myers Squibb Co, Wallingford, CT USA. NR 0 TC 59 Z9 59 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S340 EP S341 DI 10.1097/01.JTO.0000283155.03863.e7 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600241 ER PT J AU Lynch, TJ AF Lynch, Thomas J. TI How to integrate biomarkers in clinical trials SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract ID CELL LUNG-CANCER C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S296 EP S297 DI 10.1097/01.JTO.0000283074.31443.4f PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600160 ER PT J AU Merrick, DT Buyers, E Miller, YE Keith, RL Kennedy, T Franklin, WA AF Merrick, Daniel T. Buyers, Eliazbeth Miller, York E. Keith, Robert L. Kennedy, Timothy Franklin, Wilbur A. TI Angiogenesis in bronchial dysplasia and angiogenic squamous dysplasia is associated with the development of immature vasculature SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Colorado, HSC, Denver VAMC, Dept Pathol, Denver, CO 80202 USA. Univ Colorado, Denver VAMC, Dept Pulm Med, Denver, CO 80202 USA. St Lukes Hosp, Dept Pulm Med, Denver, CO USA. Univ Colorado, HSC, Dept Pathol, Denver, CO 80202 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S442 EP S442 DI 10.1097/01.JTO.0000283360.45365.fe PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600444 ER PT J AU Merrick, DT Franklin, WA Keith, RL Hirsch, FR Kennedy, T Braudrick, S Miller, YE AF Merrick, Daniel T. Franklin, Wilbur A. Keith, Robert L. Hirsch, Fred R. Kennedy, Timothy Braudrick, Sarah Miller, York E. TI Outcomes in bronchial dysplasia: persistence of lesions and associations with development of invasive non-small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Colorado, Denver VAMC, Dept Pathol, Denver, CO USA. Univ Colorado HSC, Dept Pulm Med, Denver, CO USA. Univ Colorado, Dept Med, Denver, CO USA. St Lukes Hosp, Dept Pulm Med, Denver, CO USA. Univ Colorado, Canc Ctr, Denver, CO 80309 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S331 EP S331 DI 10.1097/01.JTO.0000283136.37929.6b PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600222 ER PT J AU Park, JO Zhao, F Zejnullahu, K Normant, E Engelman, JA Johnson, BE Janne, PA AF Park, Joon Oh Zhao Feng Zejnullahu, Kreshnik Normant, Emmanuel Engelman, Jeffrey A. Johnson, Bruce E. Janne, Pasi A. TI IPI-504, a novel HSP90 inhibitor is effective in EGFR T790M and non-T790M gefitinib-resistant lung cancer cell lines. SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Infin Pharmaceut Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S361 EP S361 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600280 ER PT J AU Plate, JM Iyengar, RM Sutton, P Bonomi, P AF Plate, Janet M. Iyengar, Ravi M. Sutton, Parnetta Bonomi, Philip TI Nrdp1 and ErbB3 expression in non-small cell lung cancer cell lines. SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Cologne, Max Planck Inst Neurol Res, Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Broad Inst, MIT, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S381 EP S381 DI 10.1097/01.JTO.0000283233.61089.02 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600319 ER PT J AU Ramalingam, SS Dahlberg, SE Langer, CJ Gray, R Belani, CP Brahmer, JR Sandler, A Schiller, JH Johnson, DH AF Ramalingam, Suresh S. Dahlberg, Suzanne E. Langer, Corey J. Gray, Robert Belani, Chandra P. Brahmer, Julie R. Sandler, Alan Schiller, Joan H. Johnson, David H. TI Outcomes for elderly advanced stage non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P): Analysis of Eastern Cooperative Oncology Group (ECOG) 4599 study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Johns Hopkins Univ, Baltimore, MD USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. RI Johnson, David/A-7437-2009 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S468 EP S468 DI 10.1097/01.JTO.0000283415.19240.46 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600499 ER PT J AU Shimamura, T Greulich, H Solca, FF Wong, KK AF Shimamura, Takeshi Greulich, Heidi Solca, Flavio F. Wong, Kwok-Kin TI Efficacy of BIBW 2992, a potent irreversible inhibitor of EGFR and HER2 in human NSCLC xenografts and in a transgenic mouse lung-cancer model SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Broad Inst, MIT, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S380 EP S380 DI 10.1097/01.JTO.0000283232.53465.68 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600318 ER PT J AU Thomas, RK Meyerson, M AF Thomas, Roman K. Meyerson, Matthew TI Translational lung cancer genomics SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Univ Cologne, Max Planck Inst Neurol Res, Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Broad Inst, MIT, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S381 EP S382 DI 10.1097/01.JTO.0000283234.99206.70 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600320 ER PT J AU Yonesaka, K Zejnullahu, K Homes, AJ Johnson, BE Janne, PA AF Yonesaka, Kimio Zejnullahu, Kreshnik Homes, Alison J. Johnson, Bruce E. Janne, Pasi A. TI Presence of amphiregulin autocrine-loop predicts in vitro sensitivity of EGFR wild type NSCLC and HNSCC cell lines to gefitinib and cetuximab SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Lowe Ctr Thorac Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2007 VL 2 IS 8 SU S BP S382 EP S382 DI 10.1097/01.JTO.0000283235.99206.39 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 199IE UT WOS:000248688600321 ER PT J AU Velmahos, GC Spaniolas, K Duggan, M Alam, HB Tabbara, M De Moya, M Vosburgh, K AF Velmahos, George C. Spaniolas, Konstantinos Duggan, Michael Alam, Hasan B. Tabbara, Malek De Moya, Marc Vosburgh, Kirby TI Abdominal insufflation for control of bleeding after severe splenic injury SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 28-30, 2006 CL New Orleans, LA SP Amer Assoc Surg Trauma DE exsanguinations; bleeding; spleen; injury; insufflation ID TRAUMA; HEMORRHAGE; MORTALITY; DEATHS; TIME AB Background: To date, there is no rapid method to control intracavitary bleeding without an operation. Over 70% of trauma deaths from uncontrollable internal bleeding occur early after injury before an operation is feasible. Abdominal insufflation (AI) by carbon dioxide has been shown to reduce the rate of bleeding after intra-abdominal injury in pigs. The concept was proven in highly lethal models of severe vascular and liver injuries. Similar injuries in humans would result in immediate exsanguination and low likelihood for any intervention. We hypothesized that AI would similarly reduce bleeding in a model of moderate but persistent bleeding from a splenic injury. This model represents a clinically relevant scenario, of continuous bleeding, which does not kill the patient immediately but may ultimately result in death if not managed early. Methods: A new model of splenic injury was applied on 19 pigs, randomized to standard resuscitation (SR, N = 10) or standard resuscitation with AI to 20 cm H2O (SRAI, N = 9). For 30 minutes, the pigs were bled and the hemodynamics recorded. At 30 minutes, the abdomen was opened and free blood was collected and measured. Outcomes were blood loss, mean arterial pressure, hemoglobin, lactate levels, and arterial blood gases at the end of the experiment. Results: All pigs survived to the end of the experiment. Blood loss was lower (1,114 +/- 486 mL vs. 666 +/- 323 mL, p = 0.03) and final mean arterial pressure higher (64 +/- 12 mm Hg vs. 54 +/- 8 mm Hg, p = 0.04) in SRAI when compared with those in SR animals. Heart rate, arterial blood gases, oxygen saturation, hemoglobin, and lactate levels were similar in the two groups, except there was a more acidotic pH among SRAI animals (7.27 +/- 0.06 vs. 7.47 +/- 0.21, p = 0.02). Conclusions: AI is a novel method to control intra-abdominal bleeding temporarily. With proper portable instruments and first-responder training, this is a technique that can potentially be used in the field to save lives from intra-abdominal exsanguination. C1 Massachusetts Gen Hosp, Div Trauma, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. CIMIT, Boston, MA USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI Tabbara, Malek/0000-0003-1046-7803 NR 17 TC 12 Z9 15 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 AUG PY 2007 VL 63 IS 2 BP 285 EP 288 DI 10.1096/TA.0b013e3180d0a6ea PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 200AC UT WOS:000248735300007 PM 17693825 ER PT J AU Wagner, AW Rizvi, SL Harried, MS AF Wagner, Amy W. Rizvi, Shireen L. Harried, Melanie S. TI Applications of dialectical Behavior therapy to the treatment of complex trauma-related problems: When one case formulation does not fit all SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2006 CL Los Angeles, CA SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; BORDERLINE PERSONALITY-DISORDER; FEMALE ASSAULT VICTIMS; CHILDHOOD SEXUAL-ABUSE; RANDOMIZED-TRIAL; EXPERIENCES; SURVIVORS; EXPOSURE AB In this article, the authors take the perspective that effective treatment of complex trauma-related problems requires, in the absence of empirically supported treatments, a reliance on theory, idiographic assessment, and empirically supported principles of change. Dialectical behavior therapy (DBT; M. M Linehan, 1993) is used to demonstrate the applicability of this approach to the treatment of multiproblem, heterogeneous populations in general Two case studies are presented that highlight the utility of DBT principles to complex trauma-related problems specifically. C1 Portland VA Med Ctr, Portland, OR 97207 USA. New Sch Social Res, Dept Psychol, New York, NY 10011 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Wagner, AW (reprint author), Portland VA Med Ctr, Box 1035, Portland, OR 97207 USA. EM amy.wagner@va.gov NR 23 TC 24 Z9 25 U1 2 U2 15 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 AUG PY 2007 VL 20 IS 4 BP 391 EP 400 DI 10.1002/jts.20268 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 206KX UT WOS:000249183400003 PM 17721961 ER PT J AU Yehuda, R Flory, JD AF Yehuda, Rachel Flory, Janine D. TI Differentiating biological correlates of risk, PTSD, and resilience following trauma exposure SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2006 CL Los Angeles, CA SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; PERIPHERAL MONONUCLEAR LEUKOCYTES; BRAIN; VULNERABILITY; SENSITIVITY; CORTISOL; RECOVERY; SYSTEM; FUTURE; DHEA AB Risk and resilience factors presumably explain the individual differences in the response to adversity. However little is known about how such factors are related. Risk and protective factors may reflect a quantitative difference along a single dimension (e.g., low IQ might be associated with risk and high IQ with resilience); however they may also refer to orthogonal constructs that interact and/or moderate stress effects to increase or diminish the probability of developing trauma-related psychopathology (e.g., good coping could offset low IQ). The authors illustrate experimental strategies for distinguishing between these possibilities for any putative measure relating to symptom development, using a database that includes published and unpublished psychological and biological variables from a relatively homogenous cohort of exposed and nonexposed veterans. C1 Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY, Queens Coll, Dept Psychol, Flushing, NY USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov FU NIMH NIH HHS [R01 MH064675-02, R01 MH64104-01] NR 36 TC 47 Z9 47 U1 2 U2 8 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 AUG PY 2007 VL 20 IS 4 BP 435 EP 447 DI 10.1002/jts.20260 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 206KX UT WOS:000249183400007 PM 17721957 ER PT J AU Schlenger, WE Kulka, RA Fairbank, JA Hough, RL Jordan, BK Marmar, CR Weiss, DS AF Schlenger, William E. Kulka, Richard A. Fairbank, John A. Hough, Richard L. Jordan, B. Kathleen Marmar, Charles R. Weiss, Daniel S. TI The psychological risks of Vietnam: The NVVRS perspective SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2006 CL Los Angeles, CA SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; DIAGNOSTIC INTERVIEW SCHEDULE; PSYCHIATRIC-DIAGNOSIS; WAR; METAANALYSIS; RELIABILITY; VETERANS; VALIDITY; EXPOSURE; TRAUMA AB In recent years, controversy concerning the psychological consequences of service in the Vietnam war has rearisen. In this article, the Co-Principal Investigators of the National Vietnam Veterans Readjustment Study (NVVRS) provide a perspective on new findings reported by B. P Dohrenwend et al. (2006) that addresses criticisms of the NVVRS PTSD (posttraumatic stress disorder) prevalence findings, and on a perspective that was provided by R. J. McNally (2006) in an accompanying commentary. They find that Dohrenwend et al. study, which evaluated empirically a variety of the critics' alternative explanations and found little support for any of them, represents a landmark contribution to the trauma field. However, they found that McNally's commentary misrepresented the history and context of the NVVRS, and then misinterpreted Dohrenwend et al. findings and their importance. C1 Abt Associates Inc, Durham, NC 27703 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. Univ New Mexico, Dept Psychiat, Dept Family & Community Med, Albuquerque, NM 87131 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RTI Int, Res Triangle Pk, NC USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Schlenger, WE (reprint author), Abt Associates Inc, 4620 Creekstone Dr,Suite 190, Durham, NC 27703 USA. EM bill_schlenger@abtassoc.com RI Fairbank, John/F-8972-2013 OI Fairbank, John/0000-0003-2604-7256 NR 34 TC 9 Z9 9 U1 0 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 AUG PY 2007 VL 20 IS 4 BP 467 EP 479 DI 10.1002/jts.20264 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 206KX UT WOS:000249183400009 PM 17721970 ER PT J AU Brailey, K Vasterling, JJ Proctor, SP Constans, JI Friedman, MJ AF Brailey, Kevin Vasterling, Jennifer J. Proctor, Susan P. Constans, Joseph I. Friedman, Matthew J. TI PTSD symptoms, life events, and unit cohesion in US soldiers: Baseline findings from the neurocognition deployment health study SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WAR-ZONE; MILITARY PERSONNEL; VIETNAM VETERANS; SOCIAL SUPPORT; COMBAT; FEMALE; IRAQ; DISINTEGRATION; PREMILITARY AB Relationships among a modifiable situational factor (unit cohesion), Prior stressful life events, and posttraumatic stress disorder (PTSD) symptoms were assessed in 1,579 U.S. Army soldiers with no history of contemporary war zone deployment. It was predicted that unit cohesion would attenuate the dose-response relationship between past stressor exposures and PTSD symptoms at relatively moderate levels of exposure. Consistent with this hypothesis, regression analysis revealed that life experiences and unit cohesion strongly and independenty predicted PTSD symptoms, and that unit cohesion attenuated the impact of life experiences on PTSD. Some military personnel reported significant predeployment, stress-related symptoms. These symptoms may serve as vulnerabilities that could potentially be activated by subsequent war-zone deployment. Higher predeployment unit cohesion levels appear to ameliorate such symptoms, potentially lessening future vulnerability. C1 VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. Tulane Univ, New Orleans, LA 70118 USA. SE Louisiana Vet Hlth Care Syst, New Orleans, LA USA. USA, Environm Med Res Inst, VA Boston HealthCare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Natl Ctr PTSD, White River Jct, VT USA. Dartmouth Coll, Sch Med, Hanover, NH USA. RP Brailey, K (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, Jamaica Plain Campus 150 s Huntington Ave, Boston, MA 02130 USA. EM Kevin.Brailey@va.gov NR 39 TC 86 Z9 87 U1 3 U2 8 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 AUG PY 2007 VL 20 IS 4 BP 495 EP 503 DI 10.1002/its.20234 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 206KX UT WOS:000249183400012 PM 17721953 ER PT J AU Lester, KM Milby, JB Schumacher, JE Vuchinich, R Person, S Clay, OJ AF Lester, Kristin M. Milby, Jesse B. Schumacher, Joseph E. Vuchinich, Rudolph Person, Sharina Clay, Olivio J. TI Impact of Behavioral contingency management intervention on coping Behaviors and PTSD symptom reduction in cocaine-addicted homeless SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE-USE; COMORBIDITY; STRATEGIES; DEPENDENCE; RESPONSES; EFFICACY; THERAPY; STYLE; RATES AB The purpose of this study was to examine changes in posttrauma symptoms among 118 homeless cocaine-dependent adults participating in a randomly controlled trial studying effective treatments for dually diagnosed homeless individuals. Among those with trauma exposure and PTSD symptoms, the group receiving more behaviorally intensive, contingency management treatment had significantly greater reductions in PTSD symptomatology than did the group receiving less-intensive treatment. Regression analyses revealed that greater positive distraction coping and lower negative avoidance coping at baseline, in addition to changes in avoidance coping over the 6-month study period, were significantly related to greater symptom and severity reductions. The study provides some initial evidence of important treatment outcomes other than abstinence in addiction-related interventions. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. RP Lester, KM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM kristin.lester@va.gov FU NIDA NIH HHS [1R01 DA11789-01A1] NR 34 TC 6 Z9 7 U1 1 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 AUG PY 2007 VL 20 IS 4 BP 565 EP 575 DI 10.1002/jts.20239 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 206KX UT WOS:000249183400018 PM 17721968 ER PT J AU Markiewicz, MR Lukose, MA Margarone, JE Barbagli, G Miller, KS Chuang, SK AF Markiewicz, Michael R. Lukose, Melissa A. Margarone, Joseph E., III Barbagli, Guido Miller, Kennon S. Chuang, Sung-Kiang TI The oral mucosa graft: A systematic review SO JOURNAL OF UROLOGY LA English DT Review DE buccal mucosa; hypospadias; epispadias; oral mucosa; urethral stricture ID URETHRAL STRICTURE REPAIR; TERM-FOLLOW-UP; AUTOLOGOUS BUCCAL MUCOSA; ONLAY GRAFT; HYPOSPADIAS REPAIR; PENILE SKIN; ONE-STAGE; BULBAR URETHROPLASTY; ADULT PATIENTS; RECONSTRUCTION AB Purpose: We provide the reader with a critical, nonbiased, systematic review of current and precedent literature regarding the use of oral mucosa in the reconstruction of urethral defects associated with stricture and hypospadias/epispadias. Materials and Methods: We reviewed pertinent English literature from January 1966 through August 1, 2006 via the databases MEDLINE/PubMed, the Cochrane Library, and EMBASE Drugs and Pharmacology regarding the use of oral mucosa graft urethroplasty in the reconstruction of urethral defects associated with stricture and hypospadias/epispadias. Bibliographies of pertinent articles were explored for additional important literature. Results: Data were stratified among studies that only used oral mucosa graft urethroplasty in the reconstruction of urethral defects associated with stricture, and those that used oral mucosa graft urethroplasty in the reconstruction of urethral defects associated with hypospadias/epispadias. Recipient site success in the reconstruction of defects associated with stricture was significantly associated with the location of graft placement (ventral vs dorsal, p < 0.001) when an onlay graft was used. Hypospadias/epispadias recipient site success was significantly associated with the type of graft used (tube vs onlay, p < 0.001), and by the site of oral mucosa harvest (labial vs buccal, p < 0.001). Other perioperative and patient oriented variables were not significantly associated with success at the recipient site. Conclusions: The oral mucosa is a viable source of donor tissue displaying many characteristics of the ideal urethral graft. There are numerous variations of the oral mucosa graft urethroplasty technique. Herein comparisons are made. C1 SUNY Buffalo, Dept Oral & Maxillofacial Surg, Buffalo, NY 14260 USA. SUNY Buffalo, Sch Dent Med, Buffalo, NY 14260 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. Ctr Reconstruct Urethral Surg, Arezzo, Italy. Brown Univ, Sch Med, Dept Surg, Div Urol, Providence, RI 02912 USA. RP Markiewicz, MR (reprint author), 6490 Main St,Suite 3, Williamsville, NY USA. EM michaelmarkewicz@gmail.com NR 64 TC 78 Z9 88 U1 1 U2 9 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 AUG PY 2007 VL 178 IS 2 BP 387 EP 394 DI 10.1016/j.juro.2007.03.094 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 190AH UT WOS:000248029600006 PM 17561150 ER PT J AU Olumi, AF AF Olumi, Aria F. TI The impact factors on prognosis of patients with pT3 upper urinary tract transitional cell carcinoma - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2007 VL 178 IS 2 BP 450 EP 450 DI 10.1016/j.juro.2007.03.296 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 190AH UT WOS:000248029600024 ER PT J AU Dahl, DM AF Dahl, Douglas M. TI Surgical outcomes for men undergoing laparoscopic radical prostatectomy after transurethral resection of the prostate - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Dahl, DM (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 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 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2007 VL 178 IS 2 BP 487 EP 487 DI 10.1016/j.juro.2007.03.272 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 190AH UT WOS:000248029600036 ER PT J AU D'Amico, AV Chen, MH AF D'Amico, Anthony V. Chen, Ming-Hui TI Radical prostatectomy for clinically localized, high risk prostate cancer: Critical analysis of risk assessment methods - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2007 VL 178 IS 2 BP 499 EP 499 DI 10.1016/j.juro.2007.03.328 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 190AH UT WOS:000248029600040 ER PT J AU Barry, MJ AF Barry, Michael J. TI The efficacy of written screening tools in an inner city hospital: Literacy based limitations on patient access to appropriate care - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2007 VL 178 IS 2 BP 629 EP 629 DI 10.1016/j.juro.2007.03.317 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 190AH UT WOS:000248029600077 ER PT J AU Aldaz-Carroll, L Xiao, YH Whitbeck, JC de Leon, MP Lou, H Kim, M Yu, J Reinherz, EL Isaacs, SN Eisenberg, RJ Cohen, GH AF Aldaz-Carroll, Lydia Xiao, Yuhong Whitbeck, J. Charles de Leon, Manuel Ponce Lou, Huan Kim, Mikyung Yu, Jessica Reinherz, Ellis L. Isaacs, Stuart N. Eisenberg, Roselyn J. Cohen, Gary H. TI Major neutralizing sites on vaccinia virus glycoprotein B5 are exposed differently on variola virus ortholog B6 SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR ENVELOPED VIRUS; HERPESVIRUS ENTRY MEDIATOR; OUTER-MEMBRANE PROTEINS; 2 INFECTIOUS FORMS; MONOCLONAL-ANTIBODIES; SMALLPOX VACCINATION; PROTECTS MICE; LOCALIZATION; COMPLEMENT; CHALLENGE AB Immunization against smallpox (variola virus) with Dryvax, a live vaccinia virus (W), was effective, but now safety is a major concern. To overcome this issue, subunit vaccines composed of W envelope proteins from both forms of infectious virions, including the extracellular enveloped virion (EV) protein B5, are being developed. However, since B5 has 23 amino acid differences compared with its B6 variola virus homologue, B6 might be a better choice for such a strategy. Therefore, we compared the properties of both proteins using a panel of monoclonal antibodies (MAbs) to B5 that we had previously characterized and grouped according to structural and functional properties. The B6 gene was obtained from the Centers for Disease Control and Prevention, and the ectodomain was cloned and expressed in baculovirus as previously done with B5, allowing us to compare the antigenic properties of the proteins. Polyclonal antibodies to B5 or B6 cross-reacted with the heterologous protein, and 16 of 26 anti-B5 MAbs cross-reacted with B6. Importantly, 10 anti-B5 MAbs did not cross-react with B6. Of these, three have important anti-VV biologic properties, including their ability to neutralize EV infectivity and block comet formation. Here, we found that one of these three MAbs protected mice from a lethal W challenge by passive immunization. Thus, epitopes that are present on B5 but not on B6 would generate an antibody response that would not recognize B6. Assuming that B6 contains similar variola virus-specific epitopes, our data suggest that a subunit vaccine using the variola virus homologues might exhibit improved protective efficacy against smallpox. C1 Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Aldaz-Carroll, L (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, 240 S 40th St, Philadelphia, PA 19104 USA. EM lyriaaldaz@gmail.com RI Aldaz-Carroll, Lydia/A-6180-2008 FU NIAID NIH HHS [1 UC1-AI062486, AI48487, U01 AI048487, U19 AI057330, U54 AI057168, R21-AI53404, U54-AI57168] NR 28 TC 19 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8131 EP 8139 DI 10.1128/JVI.00374-07 PG 9 WC Virology SC Virology GA 189ZL UT WOS:000248027400032 PM 17522205 ER PT J AU Meier, A Alter, G Frahm, N Sidhu, H Li, B Bayhi, A Teigen, N Streeck, H Stellbrink, HJ Hellman, J van Lunzen, J Altfeld, M AF Meier, Angela Alter, Galit Frahm, Nicole Sidhu, Harlyn Li, Bin Bayhi, Aranya Teigen, Nickolas Streeck, Hendrik Stellbrink, Hans-Juergen Hellman, Judith van Lunzen, Jan Altfeld, Marcus TI MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded toll-like receptor ligands SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PLASMACYTOID-DENDRITIC-CELLS; T-CELL; HIV-1 INFECTION; GASTROINTESTINAL-TRACT; RIG-I; CD4(+); RESPONSES; RNA; TURNOVER AB Immune activation is a major characteristic of human immunodeficiency virus type 1 (HIV-1) infection and a strong prognostic factor for HIV-1 disease progression. The underlying mechanisms leading to immune activation in viremic HIV-1 infection, however, are not fully understood. Here we show that, following the initiation of highly active antiretroviral therapy, the immediate decline of immune activation is closely associated with the reduction of HIV-1 viremia, which suggests a direct contribution of HIV-1 itself to immune activation. To propose a mechanism, we demonstrate that the single-stranded RNA of HIV-1 encodes multiple uridine-rich Toll-like receptor 7/8 (TLR7/8) ligands that induce strong MyD88-dependent plasmacytoid dendritic cell and monocyte activation, as well as accessory cell-dependent T-cell activation. HIV-1-encoded TLR ligands may, therefore, directly contribute to the immune activation observed during viremic HIV-1 infection. These data provide an initial rationale for inhibiting the TLR pathway to directly reduce the chronic immune activation induced by HIV-1 and the associated immune pathogenesis. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. IPM Study Ctr, Hamburg, Germany. Univ Hamburg, Med Ctr Eppendorf, Infect Dis Unit, Hamburg, Germany. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org FU NIAID NIH HHS [R01 AI 067031, R01 AI50429, R01 AI050429, R01 AI067031] NR 44 TC 157 Z9 164 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8180 EP 8191 DI 10.1128/JVI.00421-07 PG 12 WC Virology SC Virology GA 189ZL UT WOS:000248027400037 PM 17507480 ER PT J AU Crawford, H Prado, JG Leslie, A Hue, S Honeyborne, I Reddy, S van der Stok, M Mncube, Z Brander, C Rousseau, C Mullins, JI Kaslow, R Goepfert, P Allen, S Hunter, E Mulenga, J Kiepiela, P Walker, BD Goulder, PJR AF Crawford, Hayley Prado, Julia G. Leslie, Alasdair Hue, Stephane Honeyborne, Isobella Reddy, Sharon van der Stok, Mary Mncube, Zenele Brander, Christian Rousseau, Christine Mullins, James I. Kaslow, Richard Goepfert, Paul Allen, Susan Hunter, Eric Mulenga, Joseph Kiepiela, Photini Walker, Bruce D. Goulder, Philip J. R. TI Compensatory mutation partially restores fitness and delays reversion of escpe mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE ESCAPE; HIV-1 INFECTION; CELL RESPONSES; VIRAL LOAD; IN-VIVO; TRANSMISSION; HLA; AIDS; POLYMORPHISMS; ASSOCIATIONS AB HLA-B*5703 is associated with effective immune control in human immunodeficiency virus type I (HIV-1) infection. Here we describe an escape mutation within the immunodominant HLA-B*5703-restricted epitope in chronic HIV-1 infection, KAFSPEVIPMF (Gag 162-172), and demonstrate that this mutation reduces viral replicative capacity. Reversion of this mutation following transmission to HLA-B*5703-negative recipients was delayed by the compensatory mutation S165N within the same epitope. These data may help explain the observed association between HLA-B*5703 and long-term control of viremia. C1 Univ Oxford, Dept Pediat, Oxford OX1 3SY, England. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, South Africa. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Univ Washington, Dept Microbiol, Sch Med, Seattle, WA 98195 USA. Univ Alabama, Birmingham, AL 35294 USA. ZEHRG, Lusaka, Zambia. Zambia Blood Transfus Serv, Lusaka, Zambia. Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Goulder, PJR (reprint author), Univ Oxford, Dept Pediat, Peter Medawar Bldg Pathogen Res,S Pk Rd, Oxford OX1 3SY, England. EM philip.goulder@ndm.ox.ac.uk OI Hue, Stephane/0000-0002-8580-6905 FU NIAID NIH HHS [2R01-AI-46995, AI-64060, P30 AI027757, R01 AI046995, R01 AI064060, R01 AI064060-03]; PHS HHS [N01-A1-15422] NR 34 TC 160 Z9 164 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 15 BP 8346 EP 8351 DI 10.1128/JVI.00465-07 PG 6 WC Virology SC Virology GA 189ZL UT WOS:000248027400053 PM 17507468 ER PT J AU Brainard, DM Tager, AM Misdraji, J Frahm, N Lichterfeld, M Draenert, R Brander, C Walker, BD Luster, AD AF Brainard, Diana M. Tager, Andrew M. Misdraji, Joseph Frahm, Nicole Lichterfeld, Mathias Draenert, Rika Brander, Christian Walker, Bruce D. Luster, Andrew D. TI Decreased CXCR3(+) CD8 T cells in advanced human immunodeficiency virus infection suggest that a homing defect contributes to cytotoxic T-Lymphocyte dysfunction SO JOURNAL OF VIROLOGY LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; CHEMOKINE RECEPTOR EXPRESSION; PRIMARY IMMUNE-RESPONSE; HIV-INFECTION; ANTIRETROVIRAL THERAPY; ALPHA-CHEMOATTRACTANT; INDUCIBLE PROTEIN-10; VIRAL REPLICATION; TYPE-1 INFECTION; DENDRITIC CELLS AB To exert their cytotoxic function, cytotoxic T-lymphocytes (CTL) must be recruited into infected lymphoid tissue where the majority of human immunodeficiency virus (W replication occurs. Normally, effector T cells exit lymph nodes (LNs) and home to peripheral sites of infection. How HIV-specific CTL migrate into lymphoid tissue from which they are normally excluded is unknown. We investigated which chemokines and receptors mediate this reverse homing and whether impairment of this homing could contribute to CTL dysfunction as HIV infection progresses. Analysis of CTL chemokine receptor expression in the blood and LNs of untreated HIV-infected individuals with stable, chronic infection or advanced disease demonstrated that LNs were enriched for CXCR3(+) CD8 T cells in all subjects, suggesting a key role for this receptor in CTL homing to infected lymphoid tissue. Compared to subjects with chronic infection, however, subjects with advanced disease had fewer CXCR3(+) CD8 T cells in blood and LNs. CXCR3 expression on bulk and HIV-specific CD8 T cells correlated positively with CD4 count and negatively with viral load. In advanced infection, there was an accumulation of HIV-specific CD8 T cells at the effector memory stage; however, decreased numbers of CXCR3(+) CD8 T cells were seen across all maturation subsets. Plasma CXCL9 and CXCL10 were elevated in both infected groups in comparison to the levels in uninfected controls, whereas lower mRNA levels of CXCR3 ligands and CD8 in LNs were seen in advanced infection. These data suggest that both CXCR3+ CD8 T cells and LN CXCR3 ligands decrease as HIV infection progresses, resulting in reduced homing of CTL into LNs and contributing to immune dysfunction. C1 Harvard Univ, Sch Med, Ctr Immunol & Inflammat Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Munich, Med Poliklin, D-8000 Munich, Germany. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM aluster@partners.org OI Brander, Christian/0000-0002-0548-5778 FU NCI NIH HHS [R01 CA 69212, R01 CA069212]; NIAID NIH HHS [K08 AI 058857, K08 AI058857, P30 AI060354] NR 63 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 16 BP 8439 EP 8450 DI 10.1128/JVI.00199-07 PG 12 WC Virology SC Virology GA 198SZ UT WOS:000248649100007 PM 17553894 ER PT J AU Yang, XZ Lipchina, I Lifton, M Wang, LP Sodroski, J AF Yang, Xinzhen Lipchina, Inna Lifton, Michelle Wang, Liping Sodroski, Joseph TI Antibody binding in proximity to the Receptor/Glycoprotein complex leads to a basal level of virus neutralization SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTION; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; AVIAN-LEUKOSIS; CCR5 RECEPTOR; VIRAL ENTRY; IN-VITRO; SUBGROUP; SARCOMA AB Hypothetically, antibodies may neutralize enveloped viruses by diverse mechanisms, such as disruption of receptor binding, interference with conformational changes required for virus entry, steric hindrance, or virus aggregation. Here, we demonstrate that retroviral infection mediated by the avian sarcoma-leukosis virus (ASLV-A) envelope glycoproteins can be neutralized by an antibody directed against a functionally unimportant component of a chimeric receptor protein. Thus, the binding of an antibody in proximity to the retroviral envelope glycoprotein-receptor complex, without binding to the entry machinery itself, results in neutralization. This finding provides additional support for the hypothesis that steric hindrance is sufficient for antibody-mediated neutralization of retroviruses. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Yang, XZ (reprint author), RE 213A,330 Brookline Ave, Boston, MA 02215 USA. EM xyangl@bidmc.harvard.edu FU NIAID NIH HHS [AI 073133, AI 39420, AI 24755, R37 AI024755, U19 AI067854, AI 67854, R01 AI039420, AI 40895, AI 42848, U01 AI067854, P30 AI042848, R01 AI040895, R21 AI064009, R01 AI073133, AI 064009] NR 25 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 16 BP 8809 EP 8813 DI 10.1128/JVI.00394-07 PG 5 WC Virology SC Virology GA 198SZ UT WOS:000248649100043 PM 17537847 ER PT J AU Jackson, ML AF Jackson, Mary Lou TI Communication with patients who have low vision SO JOURNAL OF VISUAL IMPAIRMENT & BLINDNESS LA English DT Article C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Harvard Dept Ophthalmol, Boston, MA 02114 USA. RP Jackson, ML (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Harvard Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Marylou_jackson@meei.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER FOUNDATION BLIND PI NEW YORK PA J VISUAL IMPAIRMENT BLINDNESS 11 PENN PLAZA SUITE 300, NEW YORK, NY 10001 USA SN 0145-482X J9 J VISUAL IMPAIR BLIN JI J. Vis. Impair. Blind. PD AUG PY 2007 VL 101 IS 8 BP 489 EP 493 PG 5 WC Rehabilitation SC Rehabilitation GA 204OK UT WOS:000249053700005 ER PT J AU Keithi-Reddy, SR Patel, TV Armstrong, AW Singh, AK AF Keithi-Reddy, S. R. Patel, T. V. Armstrong, A. W. Singh, A. K. TI Uremic pruritus SO KIDNEY INTERNATIONAL LA English DT Article ID HEMODIALYSIS-PATIENTS; DOUBLE-BLIND; SKIN; NALTREXONE; CROSSOVER; RELIEF; ITCH AB A 51-year-old African American male with diabetes, hypertension, and stage 5 chronic kidney disease presents with intense generalized itching of 1-month duration as well as nausea and vomiting of 3 days duration. He had no skin lesions that preceded the onset of itching. The patient described the itching as predominantly occurring during the day. He denied any occupational exposure. His past medical history was notable also for hepatitis C. His medications included aspirin, neutral protamine hagedorn insulin, calcitriol, calcium acetate, nifedipine, clonidine, lisinopril, and furosemide. He had been on these medications for more than 1 year at varying doses. Social history was significant for occasional tobacco and alcohol use as well as crack-cocaine consumption once every 4-6 weeks. There was no significant family history. Pertinent in the review of systems was the absence of a history of fever, weight loss, fatigue, or malaise. There was no history of jaundice. He denied oral or genital ulcers. Blood pressure at presentation was 158/92mm Hg and heart rate 80 beats/min. He was afebrile and had a normal respiratory rate. The patient had powdery deposits on his face. He was anicteric. He had bilateral pedal pitting edema. Examination of skin revealed generalized xerosis with multiple lichenified patches on the back, chest, abdomen, upper and lower extremities with more than 90% body surface involved. There were multiple excoriated 2-4mm nodules on the lower extremities bilaterally (Figure 1a) and on the back (Figure 1b). There were no burrows or vesicles between his finger or toe web spaces. The oral cavity and genitalia were normal. The rest of the examination was unremarkable. Blood work on admission revealed serum electrolytes within the normal range. Blood urea nitrogen, 93mg/dl (normal range 8-18mg/ dl); serum creatinine, 10.8mg/dl; blood glucose, 155mg/dl; liver function tests including transaminases and bilirubin were within normal limits; serum albumin, 3.6 g/dl (normal range 3-5 g/dl); serum calcium, 7.7mg/dl; serum phosphate, 4.4mg/dl; intactparathyroid hormone (iPTH), 266 pg/ml. White blood cell count was 9.58 x 10(6)/l (normal range 4.5-11 x 10(6)/l), white blood cell count differential: segmented neutrophils 54% (normal range 54 - 62%), lymphocytes 15.9% (normal range 25-33%), and monocytes 5.8% ( normal range 3-7%), eosinophils 24% and less than 5% band forms. Peripheral smear examination revealed anisomicrocytosis with burr cells and spherocytes. Antinuclear antibody was negative. Thyrotropic hormone was 2.38mU/ml. C1 Brigham & Womens Hosp, Div Renal, Dialysis Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Matrix Biol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Dermatol Program, Boston, MA 02114 USA. RP Singh, AK (reprint author), Brigham & Womens Hosp, Div Renal, Dialysis Serv, 75 Francis St, Boston, MA 02115 USA. EM asingh@partners.org NR 20 TC 27 Z9 32 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2007 VL 72 IS 3 BP 373 EP 377 DI 10.1038/sj.ki.5002197 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 195EC UT WOS:000248394300023 PM 17429345 ER PT J AU Noh, H King, GL AF Noh, H. King, G. L. TI The role of protein kinase C activation in diabetic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 5th Hyonam-Kidney-Laboratory-International-Diabetes Symposium CY FEB 02-03, 2007 CL Seoul, SOUTH KOREA SP Hyonam Kidney Lab Int Diabetes DE diabetic nephropathy; diabetic microvascular complications; protein kinase C ID GLOMERULAR MESANGIAL CELLS; ENDOTHELIAL GROWTH-FACTOR; PKC-BETA INHIBITOR; NITRIC-OXIDE; HIGH-GLUCOSE; ALBUMIN PERMEABILITY; OXIDATIVE STRESS; GENE-EXPRESSION; FILTRATION RATE; RATS AB Diabetic nephropathy is the leading cause of end-stage renal disease worldwide and an independent risk factor for all-cause and cardiovascular mortalities in diabetic patients. New insights into the molecular mechanisms that underlie the development and progression of microvascular complications of diabetes including nephropathy are emerging rapidly from experimental and clinical studies. Chronic hyperglycemia is a major initiator of diabetic microvascular complications. Activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway, enhanced polyol pathway, increased oxidative stress, and overproduction of advanced glycation end products have all been proposed as potential cellular mechanisms by which hyperglycemia induces diabetic vascular complications. The DAG-PKC pathway contributes to vascular function in many ways such as the regulation of endothelial permeability, vasoconstriction, extracellular matrix synthesis/turnover, cell growth, angiogenesis, cytokine activation, and leukocyte adhesion. We will briefly review the current knowledge base regarding the pathogenic role for the activation of DAG-PKC pathway in diabetic nephropathy and other microvascular complications of diabetes. The results from animal studies and key clinical studies investigating specific effects of the PKC isoforms on the renal and other vascular tissues to induce diabetic complications are also reviewed. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Room M4504,1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu NR 65 TC 14 Z9 15 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2007 VL 72 SU 106 BP S49 EP S53 DI 10.1038/sj.ki.5002386 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 196TY UT WOS:000248506300008 ER PT J AU Ardisson, L Iafrate, AJ Lewandrowski, K AF Ardisson, Linda Iafrate, A. John Lewandrowski, Kent TI An analysis of reference laboratory testing in a large urban academic medical center: The impact of new molecular diagnostic technologies SO LABMEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ardisson, L (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD AUG PY 2007 VL 38 IS 8 BP 472 EP 475 DI 10.1309/G2MM69T9C4C97WOW PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 195CZ UT WOS:000248391400007 ER PT J AU Vaidimarsdottir, U Kreicbergs, U Hauksdottir, A Hunt, H Onelov, E Henter, JL Steineck, G AF Vaidimarsdottir, Unnur Kreicbergs, Ulrika Hauksdottir, Arna Hunt, Hayley Oneloev, Erik Henter, Jan-Lnge Steineck, Gunnar TI Parents' intellectual and emotional awareness of their child's impending death to cancer: a population-based long-term follow-up study SO LANCET ONCOLOGY LA English DT Article ID NATIONWIDE; CARE; BEREAVEMENT; ANXIETY AB Background We aimed to study care-related determinants of when parents gain awareness of their child's impending death to cancer, and whether the duration of this awareness affects the parents' long-term morbidity. Methods Between August 2001 and October 2001,449 of 561 (80%) parents who had lost a child due to any malignancy in Sweden between Jan 1, 1992, and Dec 31, 1997 (identified on the Swedish Causes of Death Register), answered a 365-item postal questionnaire designed to ascertain when, before the child's actual death, they had become intellectually and emotionally aware of the child's impending death (awareness time). The primary endpoints were intellectual awareness time (defined as time between intellectual realisation that a disease is fatal and the actual time of death) and emotional awareness time (defined as time between emotional realisation that a disease is fatal and the actual time of death). Parents' awareness of less than 24 h was referred to as a short awareness time. Findings 436 parents answered the question about intellectual awareness and 433 parents answered the question about emotional awareness. 112 parents (26%) reported a short intellectual awareness time and 195 parents (45%) reported a short emotional awareness time. The risk of having short intellectual awareness time was increased if parents had absence of information on their child's fatal condition (mothers relative risk [RR] 3.6 [95% CI 2.3-5-5]; fathers 2.9 [1-8-4-5]) and if curative treatment was used towards the end of life (mothers 4.1 [2.6-6.5]; fathers 2.7 [1.7-4.2]). The risk of short emotional awareness time was increased if parents had absence of information indicating the child would die (mothers 1.5 [1.1-2.0]; fathers 1.8 [1.3-2.5]) and absence of talks about death with the other parent (mothers 1.5 [1.1-2.0]; fathers 1.7 [1.2-2.2]). Compared with fathers who had longer emotional awareness time, fathers with short emotional awareness time had an increased risk of depression (adjusted RR 1.8 [1.0-3.3]) and absence from employment due to sick leave or early retirement (RR 8.5 [1.1-67.8]) at follow-up. This difference was not noted for mothers. Interpretation Health-care professionals can influence parents' intellectual and emotional awareness of a child's impending death due to cancer. Short emotional awareness increases the risk of long-term depression in bereaved fathers. C1 Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Karolinska Inst, Dept Pathol & Oncol, Div Clin Canc Epidemiol, Stockholm, Sweden. Astrid Lindgrens Childrens Hosp, Dept Woman & Child Hlth, Childhood Canc Res Unit, Stockholm, Sweden. Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Sahlgrens Acad, Dept Oncol, Gothenburg, Sweden. RP Kreicbergs, U (reprint author), Karolinska Hosp, Div Clin Canc Epidemiol, Z5-U1, S-17176 Stockholm, Sweden. EM Ulrika.Kreicbergs@ki.se OI Steineck, Gunnar/0000-0002-0787-3969 NR 23 TC 9 Z9 10 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2007 VL 8 IS 8 BP 706 EP 714 DI 10.1016/S1470-2045(07)70209-7 PG 9 WC Oncology SC Oncology GA 200TQ UT WOS:000248786100029 PM 17644038 ER PT J AU Akst, LM Broadhurst, MS Burns, JA Zeitels, SM AF Akst, Lee M. Broadhurst, Matthew S. Burns, James A. Zeitels, Steven M. TI Microflap laryngosplasty for treating an anterior-commissure web with papillomatosis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Combined Sections of the Triological-Society CY FEB 14-18, 2007 CL Marco Isl, FL SP Triol Soc ID CLINICAL EXPERIENCE; LASER TREATMENT; SURGERY; DYSPLASIA; CO2-LASER C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabilitat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Loyola Univ, Stritch Sch Med, Dept Otolaryngol, Maywood, IL 60153 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg, 1 Bowdoin Sq 11th Floor, Boston, MA 02114 USA. EM zeitels.steven@mgh.harvard.edu 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 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2007 VL 117 IS 8 BP 1496 EP 1499 DI 10.1097/MLG.0b013e3180645d6b PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 196VR UT WOS:000248510800035 PM 17592395 ER PT J AU Burns, JA Zeitels, SM Akst, LM Broadhurst, MS Hillman, RE Anderson, R AF Burns, James A. Zeitels, Steven M. Akst, Lee M. Broadhurst, Matthew S. Hillman, Robert. E. Anderson, Rox TI 532 nm pulsed potassium-titanyl-phosphate laser treatment of laryngeal papillomatosis under general anesthesia SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Combined Sections of the Triological-Society CY FEB 14-18, 2007 CL Marco Isl, FL SP Triol Soc DE vocal fold; vocal cord; dysphonia; glottic; glottis; hoarseness; laryngoscopy; papillomatosis; potassium-titanyl-phosphate laser; photoangiolysis ID DYE-LASER; GLOTTAL PAPILLOMATOSIS; DYSPLASIA AB Objectives: Angiolytic lasers have been shown to be an effective treatment strategy for laryngeal papillomatosis. These lasers precisely target hemoglobin within the microcirculation of papillary lesions. We have previously demonstrated the advantages of the fiber-based pulsed 532-nm potassium-titanyl-phosphate (KTP) laser in an office setting (with local anesthesia). This investigation provides the first report of the pulsed-KTP laser during microlaryngoscopy under general anesthesia. Study Design: A prospective pilot study was performed in 55 adult patients with laryngeal papillomatosis to determine disease response. Methods: During suspension microlaryngoscopy, a solid-state 532 run pulsed-KTP laser was used (15 ms pulse width, 5.25-7.5 J/pulse maximum output, 2 Hz repetition rate, 0.4 mm fiber, approximately 20-80 J/cm(2) fluence) to treat laryngeal papillomatosis. All patients underwent postoperative videolaryngoscopy to assess disease regression based on a previously used rating scale. Results: Thirty-seven patients underwent 55 procedures during the 18-month study period. Near-term follow-up with an early postoperative evaluation was available in 23 patients (35 procedures). Fourteen patients (20 procedures) were geographically distant and only returned after developing symptoms with significant disease recurrence. Of the 35 procedures in which near-term follow-up was available, 90% or greater disease regression was achieved in 28 of 35 (80%), 75% to 89% disease regression was achieved in 4 of 35 (11%), and 50% to 74% disease regression in 3 of 35 (9%). Anterior-commissure disease was present in 51 of 55 (93%) cases, and no new webbing/synechia occurred. All patients reported that their vocal function improved after treatment. Conclusions: The 532 mn pulsed-KTP laser was effective for treating recurrent respiratory papillomatosis, which was similar to our experience as an office-based procedure. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. Loyola Univ, Stritch Sch Med, Dept Otolaryngol, Maywood, IL 60153 USA. Harvard Univ, Wellman Labs Photomed, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Boston, MA USA. RP Burns, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, 1 Bowdoin Sq 11th Floor, Boston, MA 02114 USA. EM Burns.james@mgh.harvard.edu NR 15 TC 26 Z9 27 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2007 VL 117 IS 8 BP 1500 EP 1504 DI 10.1097/MLG.0b013e318064e869 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 196VR UT WOS:000248510800036 PM 17585283 ER PT J AU Pardanani, A Hood, J Lasho, T Levine, RL Martin, MB Noronha, G Finke, C Mak, CC Mesa, R Zhu, H Soll, R Gilliland, DG Tefferi, A AF Pardanani, A. Hood, J. Lasho, T. Levine, R. L. Martin, M. B. Noronha, G. Finke, C. Mak, C. C. Mesa, R. Zhu, H. Soll, R. Gilliland, D. G. Tefferi, A. TI TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations SO LEUKEMIA LA English DT Article DE myeloproliferative disorder; mutation; JAK2V617F; kinase inhibitor ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACTIVATING MUTATION; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; MYELOID METAPLASIA; MEGAKARYOBLASTIC LEUKEMIA; JAK2; MYELOFIBROSIS; V617F; JAK2(V617F) AB JAK2V617F and MPLW515L/K represent recently identified mutations in myeloproliferative disorders (MPD) that cause dysregulated JAK-STAT signaling, which is implicated in MPD pathogenesis. We developed TG101209, an orally bioavailable small molecule that potently inhibits JAK2 (IC(50) = 6 nM), FLT3 (IC(50) = 25 nM) and RET (IC(50) = 17 nM) kinases, with significantly less activity against other tyrosine kinases including JAK3 (IC(50) = 169 nM). TG101209 inhibited growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC(50) of similar to 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209-induced cell cycle arrest and apoptosis, and inhibited phosphorylation of JAK2V617F, STAT5 and STAT3. Therapeutic efficacy of TG101209 was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. TargeGen Inc, Res & Dev, San Diego, CA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu NR 23 TC 167 Z9 181 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2007 VL 21 IS 8 BP 1658 EP 1668 DI 10.1038/sj.leu.2404750 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 191ZI UT WOS:000248170100008 PM 17541402 ER PT J AU Glodek, AM Le, Y Dykxhoorn, DM Park, SY Mostoslavsky, G Mulligan, R Lieberman, J Beggs, HE Honczarenko, M Silberstein, LE AF Glodek, A. M. Le, Y. Dykxhoorn, D. M. Park, S-Y Mostoslavsky, G. Mulligan, R. Lieberman, J. Beggs, H. E. Honczarenko, M. Silberstein, L. E. TI Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells SO LEUKEMIA LA English DT Article DE CXCL12; FAK; hematopoiesis; lymphopoiesis; chemokines ID PROTEIN-TYROSINE KINASE; CHEMOKINE RECEPTOR CXCR4; BONE-MARROW; PROGENITOR CELLS; B-CELLS; INTEGRIN ACTIVATION; LYMPHOCYTE ADHESION; T-LYMPHOCYTE; STEM-CELLS; FACTOR-I AB Hematopoietic stem/progenitor cells (HSC/P) reside in the bone marrow in distinct anatomic locations (niches) to receive growth, survival and differentiation signals. HSC/P localization and migration between niches depend on cell-cell and cell-matrix interactions, which result from the cooperation of cytokines, chemokines and adhesion molecules. The CXCL12-CXCR4 pathway, in particular, is essential for myelopoiesis and B lymphopoiesis but the molecular mechanisms of CXCL12 action remain unclear. We previously noted a strong correlation between prolonged CXCL12-mediated focal adhesion kinase (FAK) phosphorylation and sustained pro-adhesive responses in progenitor B cells, but not in mature B cells. Although FAK has been well studied in adherent fibroblasts, its function in hematopoietic cells is not defined. We used two independent approaches to reduce FAK expression in (human and mouse) progenitor cells. RNA interference (RNAi)-mediated FAK silencing abolished CXCL12-induced responses in human pro-B leukemia, REH cells. FAK-deficient REH cells also demonstrated reduced CXCL12-induced activation of the GTPase Rap1, suggesting the importance of FAK in CXCL12-mediated integrin activation. Moreover, in FAK(flox/flox) hematopoietic precursor cells, Cre-mediated FAK deletion resulted in impaired CXCL12-induced chemotaxis. These studies suggest that FAK may function as a key intermediary in signaling pathways controlling hematopoietic cell lodgment and lineage development. C1 Childrens Hosp, Dept Pathol, Joint Program Transfus Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR Ctr Biomed Res, Dept Pediat, Boston, MA USA. Childrens Hosp, Div Mol Med, Dept Genet, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Ophthalmol & Physiol, San Francisco, CA 94143 USA. RP Silberstein, LE (reprint author), Dept Pathol, Joint Program Transfus Med, Karp Res Bldg,Room 10217,1 Blackfan Circle, Boston, MA 02115 USA. EM leslie.silberstein@childrens.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NHLBI NIH HHS [T32 HL 066987-06, U24 HL074355-03] NR 51 TC 39 Z9 42 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2007 VL 21 IS 8 BP 1723 EP 1732 DI 10.1038/sj.leu.2404769 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 191ZI UT WOS:000248170100015 PM 17568820 ER PT J AU Sophie, A Andrew, K Lindblad-Toh, K Daly, M Hynes, RO AF Astrof, Sophie Kirb, Andrew Lindblad-Toh, Kerstin Daly, Mark Hynes, Richard O. TI Heart development in fibronectin-null mice is governed by a genetic modifier on chromosome four SO MECHANISMS OF DEVELOPMENT LA English DT Article DE fibronectin; heart development; genetic modifier; mapping ID EMBRYOS LACKING; MYOCARDIAL MIGRATION; TRANSCRIPTION FACTOR; ENDODERM FORMATION; PRECURSOR CELLS; TUBE FORMATION; MOUSE EMBRYO; ZEBRAFISH; MORPHOGENESIS; PROTEIN AB Absence of the fibronectin (FN) gene leads to early embryonic lethality in both 129S4 and C57BL/6J strains due to severe cardiovascular defects. However, heart development is arrested at different stages in these embryos depending on the genetic background. In the majority of 129S4 FN-null embryos, heart progenitors remain at their anterior bilateral positions and fail to fuse at the midline to form a heart tube. However, on the C57BL/6J genetic background, cardiac development progresses further and results in a centrally positioned and looped heart. To find factor(s) involved in embryonic heart formation and governing the extent of heart development in FN-null embryos in 129S4 and C57BL/6J strains, we performed genetic mapping and haplotype analyses. These analyses lead to identification of a significant linkage to a 1-Mbp interval on chromosome four. Microarray analysis and sequencing identified 21 genes in this region, including five that are differentially expressed between the strains, as potential modifiers. Since none of these genes was previously known to play a role in heart development, one or more of them is likely to be a novel modifier affecting cardiac development. Identification of the modifier would significantly enhance our understanding of the molecular underpinning of heart development and disease. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 MIT, Dept Biol, Canc Res Ctr, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. RP Hynes, RO (reprint author), MIT, Dept Biol, Canc Res Ctr, Howard Hughes Med Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rohynes@mit.edu OI Astrof, Sophie/0000-0001-9338-9083 NR 39 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 2007 VL 124 IS 7-8 BP 551 EP 558 DI 10.1016/j.mod.2007.05.004 PG 8 WC Developmental Biology SC Developmental Biology GA 205XB UT WOS:000249146800005 ER PT J AU Saha, S Solotaroff, R Oster, A Bindman, AB AF Saha, Somnath Solotaroff, Rachel Oster, Ady Bindman, Andrew B. TI Are preventable hospitalizations sensitive to changes in access to primary care? The case of the Oregon Health Plan SO MEDICAL CARE LA English DT Article DE preventable hospitalizations; access to care; Medicaid ID UNINSURED PREGNANT-WOMEN; SOCIOECONOMIC-STATUS; MANAGED CARE; IMPACT; MASSACHUSETTS; INSURANCE; PROVIDER; COVERAGE; STATES; RATES AB Objective: To examine whether preventable hospitalization (PH) rates are sensitive to the impact of policies aimed at improving access, such as the Oregon Health Plan (OHP), which expanded Medicaid coverage to all adults with incomes under the federal poverty level. Study Design: We conducted a retrospective, time series analysis of PH rates in Oregon from 1990 to 2000. We calculated hospitalization rates for ambulatory-care sensitive conditions for the Medicaid + uninsured population and compared average annual rates from 1990 to 1993 (pre-OHP implementation) to those from 1995 to 2000 (post-OHP implementation). We compared changes in PH rates over time in the Medicaid + uninsured group to changes in the nonMedicaid insured population. We standardized rates by age and sex and used logistic regression models to compare rates. Results: Contrary to our hypothesis, annual PH rates in the Medicaid + uninsured population increased after the eligibility expansion, from an average of 46.1 to 54.9 per 10,000 persons. This rise was significant compared with the non-Medicaid insured population, who experienced a slight decline in annual PH rates, from 26.9 to 26.1 per 10,000 (P < 0.001, after adjusting for age, sex, and rates of unpreventable hospitalizations). The increase in overall PH rates for the Medicaid + uninsured population can be explained by an increase in PH rates for the newly insured group. Conclusions: Our results suggest that PH rates may vary not only with access to primary care (inversely) but also with access to hospital care (directly). The use of PH rates as a marker of health care access should take into account these dual influences. Limita tions in available data may also contribute to perceived variation in PH rates unrelated to health care access. C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Med, Gen Internal Med Sect, Portland, OR 97207 USA. Charles B Wang Commnity Hlth Ctr, New York, NY USA. Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Saha, S (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Med, Gen Internal Med Sect, P3 HSR&D,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM sahas@ohsu.edu NR 30 TC 32 Z9 32 U1 1 U2 9 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 AUG PY 2007 VL 45 IS 8 BP 712 EP 719 DI 10.1097/MLR.0b013e318053717c PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 197BZ UT WOS:000248529700004 PM 17667304 ER PT J AU Swanson, KA Bastani, R Rubenstein, LV Meredith, LS Ford, DE AF Swanson, Karen A. Bastani, Roshan Rubenstein, Lisa V. Meredith, Lisa S. Ford, Daniel E. TI Effect of mental health care and shared decision making on patient satisfaction in a community sample of patients with depression SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE patient satisfaction; quality of care; gender; shared decision making ID MANAGED CARE; MEDICAL-CARE; QUALITY; GENDER; WOMEN; COMMUNICATION; OUTCOMES AB This study sought to understand if shared decision making and/or receipt of mental health care was associated with patient satisfaction for patients with depression and to determine whether gender modified this relationship. The data are from the Quality Improvement for Depression study, a national collaborative study of 1,481 patients diagnosed with major depression in managed care settings. The cross-sectional analyses were performed using multiple logistic regression on a sample of 1,317 patients who answered both the baseline and month six questionnaires. Shared decision making and receipt of mental health care were both positively associated with patient satisfaction. Gender was not a moderator of this relationship. Health plans may be able to improve patient satisfaction levels by teaching physicians the importance of shared decision making. Contrary to expectations, patient gender made no difference in the effects of quality of care on patient satisfaction. C1 Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles, Ctr Study Hlth Care Provider Behav, Los Angeles, CA USA. RAND Corp, Santa Monica, CA 90406 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Swanson, KA (reprint author), Los Angeles Cty Dept Hlth Serv, Off Ambulatory Care, 313 N Figueroa St,Rm 704, Los Angeles, CA 90012 USA. EM kswanson@ladhs.org FU AHRQ HHS [R03 HS11407-01] NR 39 TC 42 Z9 44 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD AUG PY 2007 VL 64 IS 4 BP 416 EP 430 DI 10.1177/1077558707299479 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 194WE UT WOS:000248373700004 PM 17684110 ER PT J AU Lasser, T Ntziachristos, V AF Lasser, Tobias Ntziachristos, Vasilis TI Optimization of 360 degrees projection fluorescence molecular tomography SO MEDICAL IMAGE ANALYSIS LA English DT Article DE fluorescence molecular tomography; Singular-value analysis ID DIFFUSE OPTICAL TOMOGRAPHY; SINGULAR-VALUE ANALYSIS; BREAST; RECONSTRUCTION; APPROXIMATION; SPECTROSCOPY; GEOMETRIES; SYSTEM; TISSUE; PROBES AB Fluorescence tomography of tissues has been generally limited to systems that require fixed geometries or measurements employing fibers. Certain technological advances however, have more recently allowed the development of complete-projection 360 tomographic approaches using non-contact detection and illumination. Employing multiple illumination projections and CCD cameras as detection devices vastly increases the information content acquired, posing non-trivial computational and experimental requirements. In this paper, we use singular-value analysis to optimize experimental parameters relevant to the design and operation of emerging 360 fluorescence molecular tomography (FMT) methods and systems for small animal imaging. We present the theoretical and experimental methodology, optimization results and their experimental validation. We further discuss how these results can be employed to improve the performance of existing FMT systems and guide the design of new systems. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Munich Technol, Dept Informat, D-85748 Garching, Germany. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lasser, T (reprint author), Univ Munich Technol, Dept Informat, Boltzmannstr 3, D-85748 Garching, Germany. EM lasser@in.tum.de FU NIEHS NIH HHS [R43-ES012360] NR 26 TC 49 Z9 50 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 J9 MED IMAGE ANAL JI Med. Image Anal. PD AUG PY 2007 VL 11 IS 4 BP 389 EP 399 DI 10.1016/j.media.2007.04.003 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 201VQ UT WOS:000248861100006 PM 17524701 ER PT J AU Lu, HM Brett, R Sharp, G Safai, S Jiang, S Flanz, J Kooy, H AF Lu, Hsiao-Ming Brett, Robert Sharp, Gregory Safai, Soiros Jiang, Steve Flanz, Jay Kooy, Hanne TI A respiratory-gated treatment system for proton therapy SO MEDICAL PHYSICS LA English DT Article DE proton gating; time delay ID RADIATION-THERAPY; RADIOTHERAPY; RANGE AB Proton therapy offers the potential for excellent dose conformity and reduction in integral dose. The superior dose distribution is, however, much more sensitive to changes in radiological depths along the beam path than for photon fields. Respiratory motion can cause such changes for treatments sites like lung, liver, and mediastinum and thus affect the proton dose distribution significantly. We have implemented and commissioned a respiratory-gated system for range-modulated treatment fields. The gating system was designed to ensure that each gate always contains complete modulation cycles so that for any beam segment the delivered dose has the planned depth-dose distribution. Measurements have been made to estimate the time delays for the various components of the system. The total delay between the actual motion and the beam on/off control is in the range of 65-195 ms. Time-resolved dose measurements and film tests were also conducted to examine the overall gating effect. (c) 2007 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02214 USA. RP Lu, HM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02214 USA. EM hmlu@partners.org FU NCI NIH HHS [5 P01 CA21239-24] NR 11 TC 22 Z9 23 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2007 VL 34 IS 8 BP 3273 EP 3278 DI 10.1118/1.2756602 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 202IP UT WOS:000248895500019 PM 17879790 ER PT J AU Sisterson, JM Burr, FH AF Sisterson, J. M. Burr, Francis H. TI Status of cross section measurements for neutron-induced reactions needed to understand cosmic ray interactions SO METEORITICS & PLANETARY SCIENCE LA English DT Meeting Abstract CT 70th Annual Meeting of the Meteoritical-Society CY AUG 13-17, 2007 CL Tucson, AZ SP Meteorit Soc, Univ Arizona Lunar & Planetary Lab, Univ Arizona Dept Geosci, Univ Arizona Coll Sci, Life & Planets Astrobiol Ctr, NSF Arizona AMS Lab, SW Meteorite Ctr, Steward Observ, Lunar & Planetary Inst, Natl Aeronaut & Space Adm, Planetary Sci Inst, Barringer Crater Co, Lockheed Martin, Cameca, New Wave, Planetary Studies Fdn, Thermo Finnigan, Univ Arizona Press, Tucson Visitors & Convent Bur, Univ Arizona Dept Phys ID ENERGIES C1 Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. EM jsisterson@partners.org NR 4 TC 0 Z9 0 U1 1 U2 1 PU METEORITICAL SOC PI FAYETTEVILLE PA DEPT CHEMISTRY/BIOCHEMISTRY, UNIV ARKANSAS, FAYETTEVILLE, AR 72701 USA SN 1086-9379 J9 METEORIT PLANET SCI JI Meteorit. Planet. Sci. PD AUG PY 2007 VL 42 SU S BP A142 EP A142 PG 1 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 200HZ UT WOS:000248755800267 ER PT J AU Pumbwe, L Skilbeck, CA Nakano, V Avila-Campos, MJ Piazza, RMF Wexler, HM AF Pumbwe, Lilian Skilbeck, Christopher A. Nakano, Viviane Avila-Campos, Mario J. Piazza, Roxane M. F. Wexler, Hannah M. TI Bile salts enhance bacterial co-aggregation, bacterial-intestinal epithelial cell adhesion, biofilm formation and antimicrobial resistance of Bacteroides fragilis SO MICROBIAL PATHOGENESIS LA English DT Article DE colonization; membrane; signaling; stress; tolerance ID ESCHERICHIA-COLI; VIBRIO-CHOLERAE; SALMONELLA-TYPHIMURIUM; ELECTRON MICROSCOPY; ANAEROBIC-BACTERIA; PROTEOMIC ANALYSIS; DNA INVERSIONS; EFFLUX SYSTEM; EXPRESSION; IDENTIFICATION AB Bacteroides fragilis is the most common anaerobic bacterium isolated from human intestinal tract infections. Before B. fragilis interacts with the intestinal epithelial cells, it is exposed to bile salts at physiological concentrations of 0.1-1.3%. The aim of this study was to determine how pre-treatment with bile salts affected B. fragilis cells and their interaction with intestinal epithelial cells. B. fragilis NCTC9343 was treated with conjugated bile salts (BSC) or non-conjugated bile salts (BSM). Cellular ultrastructure was assessed by electron microscopy, gene expression was quantified by comparative quantitative real-time RT-PCR. Adhesion to the HT-29 human intestinal cell line and to PVC microtitre plates (biofilm formation) was determined. Exposure to 0.15% BSC or BSM resulted in overproduction of fimbria-like appendages and outer membrane vesicles, and increased expression of genes encoding RND-type efflux pumps and the major outer membrane protein, OmpA. Bile salt-treated bacteria had increased resistance to structurally unrelated antimicrobial agents and showed a significant increase in bacterial co-aggregation, adhesion to intestinal epithelial cells and biofilm formation. These data suggest that bile salts could enhance intestinal colonization by B. fragilis via several mechanisms, and could therefore be significant to host-pathogen interactions. Published by Elsevier Ltd. C1 Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Lab Anaeorbios, BR-05508 Sao Paulo, Brazil. Inst Butantan, Bacteriol Lab, Sao Paulo, Brazil. RP Pumbwe, L (reprint author), Wadsworth Anaerobe Lab, Bldg 304,Room E3-224,GLAVAHCS 691-151J, Los Angeles, CA 90073 USA. EM lilskil@ucla.edu RI Nakano, Viviane/D-7955-2012; Avila-Campos, Mario/D-7727-2012; Piazza, Roxane Maria/K-9807-2016 OI Avila-Campos, Mario/0000-0002-2378-7251; NR 44 TC 43 Z9 44 U1 0 U2 16 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD AUG-SEP PY 2007 VL 43 IS 2-3 BP 78 EP 87 DI 10.1016/j.micpath.2007.04.002 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA 195FM UT WOS:000248397900003 PM 17524609 ER PT J AU Washington, DL Kleimann, S Michelini, AN Kleimann, KM Canning, M AF Washington, Donna L. Kleimann, Susan Michelini, Ann N. Kleimann, Kristin M. Canning, Mark TI Women veterans' perceptions and decision-making about veterans affairs health care SO MILITARY MEDICINE LA English DT Article; Proceedings Paper CT National Meeting of the VA-Health-Services-Research-and-Development-Service CY MAR 10, 2004 CL Washington, DC SP VA Hlth Serv Res Dev Serv ID MEDICAL-CENTER; AVAILABILITY AB The increase in women in the military is reshaping the veteran population and Veterans Affairs (VA) health care delivery imperatives. To determine women veterans' perspectives and decision-making about VA health care use, we conducted six focus groups (four VA users and two nonusers) and identified key themes. Barriers to VA use for both VA users and nonusers included lack of information about eligibility and available services. Nonusers often assumed the VA did not provide women's health care. All groups emphasized they required a health care system focused on quality and sensitivity to women's health issues. However, users and nonusers differed in perceptions of VA quality. VA environment and quality concerns led many women to limit their VA use to women's clinics. These qualitative findings provide a context to highlight where interventions and policies suggested by quantitative findings should focus. Dissemination of accurate information about VA eligibility and services, and continued responsiveness to women's perceptions of care are indicated. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Kleimann Commun Grp, Washington, DC 20005 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 11G, Los Angeles, CA 90073 USA. NR 19 TC 25 Z9 25 U1 0 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD AUG PY 2007 VL 172 IS 8 BP 812 EP 817 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 201JW UT WOS:000248828400006 PM 17803071 ER PT J AU Bean-Mayberry, BA Yano, EM Caffrey, CD Altman, L Washington, DL AF Bean-Mayberry, Bevanne A. Yano, Elizabeth M. Caffrey, Cynthia D. Altman, Lisa Washington, Donna L. TI Organizational characteristics associated with the availability of women's health clinics for primary care in the Veterans Health Administration SO MILITARY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Health-Services-Research CY JUN 26-28, 2005 CL Boston, MA SP Amer Acad Hlth Serv Res ID PATCHWORK QUILT AB Objective: Women's health clinics (WHCs) offering integrated primary care (PC) and gender-specific services reduce fragmentation and improve quality of care for women. Our objective was to understand organizational influences on the development of WHCs for PC delivery in Veterans Health Administration (VA) facilities. Methods: We surveyed PC directors at 219 VA facilities about the presence of separate WHCs for PC and evaluated organizational characteristics (e.g., authority, staffing, and resources) associated with their development. Results: One hundred thirty-three VA medical centers (61%) have established WHCs for PC. VA facilities with WHCs for PC were significantly more likely to have PC leadership distinct from subspecialty care (odds ratio = 3.62; 95% confidence interval, 1.45-9.05). Local PC staff mix, team structure, and resource characteristics were not associated with WHCs. Conclusions: With the growth of women in the military and, in turn, in the VA, autonomy of PC leadership may drive VA-based innovations in women's health. C1 VA Greater Los Angeles Hlth Serv Res & Dev, Ctr Excellence, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Off Acad Affiliat, Dept Vet Affairs, Washington, DC 20420 USA. Kaiser Permanente So Calif, Santa Clarita, CA 91355 USA. VA Greater Los Angeles Healthcare Syst, Ambulatory Care Serv Line, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. RP Bean-Mayberry, BA (reprint author), VA Greater Los Angeles Hlth Serv Res & Dev, Ctr Excellence, Ctr Study Healthcare Provider Behav, 16111 Plummer St 152, Sepulveda, CA 91343 USA. NR 19 TC 14 Z9 14 U1 0 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD AUG PY 2007 VL 172 IS 8 BP 824 EP 828 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 201JW UT WOS:000248828400008 PM 17803073 ER PT J AU Li, LJ Zhang, L Zhang, XP Yan, Q Minamishima, YA Olumi, AF Mao, M Bartz, S Kaelin, WG AF Li, Lianjie Zhang, Liang Zhang, Xiaoping Yan, Qin Minamishima, Yoji Andrew Olumi, Aria F. Mao, Mao Bartz, Steven Kaelin, William G., Jr. TI Hypoxia-inducible factor linked to differential kidney cancer risk seen with type 2A and type 2B VHL mutations SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LINDAU TUMOR-SUPPRESSOR; RENAL-CELL-CARCINOMA; GENE-PRODUCT; PROLYL HYDROXYLASE; UBIQUITIN LIGASE; VASCULAR TUMORS; FACTOR-ALPHA; E-CADHERIN; HIF-ALPHA; NUDE-MICE AB Clear cell carcinoma of the kidney is a major cause of mortality in patients with von Hippel-Lindau (VHL) disease, which is caused by germ line mutations that inactivate the VHL tumor suppressor gene. Biallelic VHL inactivation, due to mutations or hypermethylation, is also common in sporadic clear cell renal carcinomas. The VHL gene product, pVHL, is part of a ubiquitin ligase complex that targets the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for destruction under well-oxygenated conditions. All VHL mutations linked to classical VHL disease compromise this pVHL function although some missense mutations result in a low risk of kidney cancer (type 2A VHL disease) while others result in a high risk (type 2B VHL disease). We found that type 2A mutants were less defective than type 2B mutants when reintroduced into VHL-/- renal carcinoma cells with respect to HIF regulation. A stabilized version of HIF2 alpha promoted tumor growth by VHL-/- cells engineered to produce type 2A mutants, while knock-down of HIF2 alpha in cells producing type 2B mutants had the opposite effect. Therefore, quantitative differences with respect to HIF deregulation are sufficient to account for the differential risks of kidney cancer linked to VHL mutations. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02115 USA. Rosetta Inpharmat LLC, Seattle, WA 98109 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 457, Boston, MA 02115 USA. EM William_kaelin@dfci.harvard.edu RI Yan, Qin/E-8893-2012; Minamishima, Yoji/E-5380-2010 OI Yan, Qin/0000-0003-4077-453X; Minamishima, Yoji/0000-0001-7995-9318 NR 79 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2007 VL 27 IS 15 BP 5381 EP 5392 DI 10.1128/MCB.00282-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 192WL UT WOS:000248234000011 PM 17526729 ER PT J AU Pfaff, KL Straub, CT Chiang, K Bear, DM Zhou, Y Zon, LI AF Pfaff, Kathleen L. Straub, Christian T. Chiang, Ken Bear, Daniel M. Zhou, Yi Zon, Leonard I. TI The zebra fish cassiopeia mutant reveals that SIL is required for mitotic spindle organization SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CAUSES GENOME INSTABILITY; INSERTIONAL MUTAGENESIS; CHROMOSOME SEGREGATION; CELL-CYCLE; GENE; CANCER; PHOSPHORYLATION; CHECKPOINT; EXPRESSION; PROTEIN AB A critical step in cell division is formation of the mitotic spindle, which is a bipolar array of microtubules that mediates chromosome separation. Here, we report that the SCL-interrupting locus (SIL), a vertebrate-specific cytosolic protein, is necessary for proper mitotic spindle organization in zebrafish and human cells. A homozygous lethal zebrafish mutant, cassiopeia (csp), was identified by a genetic screen for mitotic mutant. csp mutant embryos have an increased mitotic index, have highly disorganized mitotic spindles, and often lack one or both centrosomes. These phenotypes are caused by a loss-of-function mutation in zebrafish sil. To determine if the requirement for SIL in mitotic spindle organization is conserved in mammals, we generated an antibody against human SIL, which revealed that SIL localizes to the poles of the mitotic spindle during metaphase. Furthermore, short hairpin RNA knockdown of SIL in human cells recapitulates the zebrafish csp mitotic spindle defects. These data, taken together, identify SIL as a novel, vertebrate-specific regulator of mitotic spindle assembly. C1 Childrens Hosp Boston, Dana Farber Canc Res Inst, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp Boston, Dana Farber Canc Res Inst, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp Boston, Dana Farber Canc Res Inst, Stem Cell Program, Karp Family Res Bldg Rm 7211,1 Blackfan Circle, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NCI NIH HHS [5R01 CA103846-02, R01 CA103846] NR 42 TC 52 Z9 53 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2007 VL 27 IS 16 BP 5887 EP 5897 DI 10.1128/MCB.00175-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197AU UT WOS:000248526100023 PM 17576815 ER PT J AU Vidal, M AF Vidal, M. TI Interactome networks SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Vidal, M.] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA USA. [Vidal, M.] Harvard Univ, CCSB, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2007 VL 6 IS 8 SU S MA 5.4 BP 51 EP 51 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 264OX UT WOS:000253299000082 ER PT J AU Orchard, S Salwinski, L Kerrien, S Montecchi-Palazzi, L Oesterheld, M Stumpflen, V Ceol, A Chatr-Aryamontri, A Armstrong, J Woollard, P Salama, JJ Moore, S Wojcik, J Bader, GD Vidal, M Cusick, ME Gerstein, M Gavin, AC Superti-Furga, G Greenblatt, J Bader, J Uetz, P Tyers, M Legrain, P Fields, S Mulder, N Gilson, M Niepmann, M Burgoon, L De Las Rivas, J Prieto, C Perreau, VM Hogue, C Mewes, HW Apweiler, R Xenarios, I Eisenberg, D Cesareni, G Hermjakob, H AF Orchard, Sandra Salwinski, Lukasz Kerrien, Samuel Montecchi-Palazzi, Luisa Oesterheld, Matthias Stuempflen, Volker Ceol, Arnaud Chatr-aryamontri, Andrew Armstrong, John Woollard, Peter Salama, John J. Moore, Susan Wojcik, Jerome Bader, Gary D. Vidal, Marc Cusick, Michael E. Gerstein, Mark Gavin, Anne-Claude Superti-Furga, Giulio Greenblatt, Jack Bader, Joel Uetz, Peter Tyers, Mike Legrain, Pierre Fields, Stan Mulder, Nicola Gilson, Michael Niepmann, Michael Burgoon, Lyle De Las Rivas, Javier Prieto, Carlos Perreau, Victoria M. Hogue, Chris Mewes, Hans-Werner Apweiler, Rolf Xenarios, Ioannis Eisenberg, David Cesareni, Gianni Hermjakob, Henning TI The minimum information required for reporting a molecular interaction experiment (MIMIx) SO NATURE BIOTECHNOLOGY LA English DT Article ID INTERACTION DATABASE; PROTEIN; RESOURCE; UPDATE AB A wealth of molecular interaction data is available in the literature, ranging from large-scale datasets to a single interaction confirmed by several different techniques. These data are all too often reported either as free text or in tables of variable format, and are often missing key pieces of information essential for a full understanding of the experiment. Here we propose MIMIx, the minimum information required for reporting a molecular interaction experiment. Adherence to these reporting guidelines will result in publications of increased clarity and usefulness to the scientific community and will support the rapid, systematic capture of molecular interaction data in public databases, thereby improving access to valuable interaction data. C1 European Bioinformat Inst, European Mol Biol Lab, Cambridge, England. Univ Calif Los Angeles, Inst Genom & Proteom, US Dept Energy, Los Angeles, CA USA. Natl Res Ctr Environm & Hlth, GSF Forschungszentrum Umwelt & Gesundheit, Inst Bioinformat, Neuherberg, Germany. Univ Roma Tor Vergata, Dept Mol Biol, Rome, Italy. GlaxoSmithkline R&D, Stevenage, Herts, England. Natl Univ Singapore, Clin Res Ctr, Singapore 117548, Singapore. Merck Serono Int SA, Geneva, Switzerland. Univ Toronto, Banting & Best Dept Med Res, Toronto, ON, Canada. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 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. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. EMBL, Heidelberg, Germany. Austrian Acad Sci, Ctr Mol Med, CeMM, A-1010 Vienna, Austria. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. Forschungszentrum Karlsruhe, Leopoldshafen, Inst Toxicol & Genet, Karlsruhe, Germany. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Inst Biol & Technol Saclay, Commiss Energie Atom, Gif Sur Yvette, France. Univ Washington, Howard Hughes Med Inst, Dept Genome Sci & Med, Seattle, WA 98195 USA. Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. Univ Maryland, Maryland Biotechnol Inst, Rockville, MD USA. Univ Giessen, D-35390 Giessen, Germany. Toxicogenom Informat & Solut, Lansing, MI USA. Univ Salamanca, Ctr Invest Canc, Canc Res Ctr, E-37008 Salamanca, Spain. Consejo Super Invest Cient, Salamanca, Spain. Univ Melbourne, Ctr Neurosci, Parkville, Vic 3052, Australia. RP Orchard, S (reprint author), European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge, England. EM orchard@ebi.ac.uk RI Bader, Joel/A-1818-2009; Bader, Gary/C-1176-2009; Hogue, Christopher/B-6726-2008; 2007, Secribsal/A-1556-2012; Uetz, Peter/A-7119-2012; Ceol, Arnaud/H-3386-2012; De Las Rivas, Javier/G-5936-2014; Superti-Furga, Giulio/F-4755-2015; Prieto, Carlos/G-2382-2016; OI Bader, Joel/0000-0002-6020-4625; Bader, Gary/0000-0003-0185-8861; Uetz, Peter/0000-0001-6194-4927; Ceol, Arnaud/0000-0001-9533-4246; De Las Rivas, Javier/0000-0002-0984-9946; Superti-Furga, Giulio/0000-0002-0570-1768; Prieto, Carlos/0000-0001-8178-9768; Kerrien, Samuel/0000-0002-3013-0469; Apweiler, Rolf/0000-0001-7078-200X; Gavin, Anne-Claude/0000-0003-4917-2340; Orchard, Sandra/0000-0002-8878-3972; Burgoon, Lyle/0000-0003-4977-5352; Hermjakob, Henning/0000-0001-8479-0262; Xenarios, Ioannis/0000-0002-3413-6841 NR 21 TC 160 Z9 162 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2007 VL 25 IS 8 BP 894 EP 898 DI 10.1038/nbt1324 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 199WL UT WOS:000248725800027 PM 17687370 ER PT J AU Park, IH Daley, GQ AF Park, In-Hyun Daley, George Q. TI Debugging cellular reprogramming SO NATURE CELL BIOLOGY LA English DT Editorial Material ID PLURIPOTENT STEM-CELLS C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Park, IH (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM George.Daley@childrens.harvard.edu NR 9 TC 6 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2007 VL 9 IS 8 BP 871 EP 873 DI 10.1038/ncb0807-871 PG 3 WC Cell Biology SC Cell Biology GA 196MM UT WOS:000248486700005 PM 17671453 ER PT J AU Rhee, J Buchan, T Zukerberg, L Lilien, J Balsamo, J AF Rhee, Jinseol Buchan, Tim Zukerberg, Lawrence Lilien, Jack Balsamo, Janne TI Cables links Robo-bound Abl kinase to N-cadherin-bound beta-catenin to mediate Slit-induced modulation of adhesion and transcription SO NATURE CELL BIOLOGY LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; REPULSIVE AXON GUIDANCE; TYROSINE-KINASE; CELL-ADHESION; C-ABL; PHOSPHORYLATION; ASSOCIATION; RECEPTORS; PROTEINS; COMPLEX AB Binding of the secreted axon guidance cue Slit to its Robo receptor results in inactivation of the neural, calcium-dependent cell cell adhesion molecule N-cadherin, providing a rapid epigenetic mechanism for integrating guidance and adhesion information. This requires the formation of a multimolecular complex containing Robo, Abl tyrosine kinase and N-cadherin. Here we show that on binding of Slit to Robo, the adaptor protein Cables is recruited to Robo-associated Abl and forms a multimeric complex by binding directly to N-cadherin-associated beta-catenin. Complex formation results in Abl-mediated phosphorylation of beta-catenin on tyrosine 489, leading to a decrease in its affinity for N-cadherin, loss of N-cadherin function, and targeting of phospho-Y489-beta-catenin to the nucleus. Nuclear beta-catenin combines with the transcription factor Tcf/Lef and activates transcription. Thus, Slit-induced formation of the Robo-N-cadherin complex results in a rapid loss of cadherin-mediated adhesion and has more lasting effects on gene transcription. C1 Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Lilien, J (reprint author), Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA. EM jack-lilien@uiowa.edu FU NEI NIH HHS [EY13363] NR 40 TC 88 Z9 90 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2007 VL 9 IS 8 BP 883 EP U30 DI 10.1038/ncb1614 PG 20 WC Cell Biology SC Cell Biology GA 196MM UT WOS:000248486700010 PM 17618275 ER PT J AU Yang, M Zhang, Y Pan, J Sun, J Liu, J Libby, P Sukhova, GK Doria, A Katunuma, N Peroni, OD Guerre-Millo, M Kahn, BB Clement, K Shi, GP AF Yang, Min Zhang, Yaou Pan, Jiehong Sun, Jiusong Liu, Jian Libby, Peter Sukhova, Galina K. Doria, Alessandro Katunuma, Nobuhiko Peroni, Odile D. Guerre-Millo, Michele Kahn, Barbara B. Clement, Karine Shi, Guo-Ping TI Cathepsin L activity controls adipogenesis and glucose tolerance SO NATURE CELL BIOLOGY LA English DT Article ID ADIPOCYTE DIFFERENTIATION; INSULIN-RECEPTORS; GENE-EXPRESSION; VASCULAR CELLS; MUSCLE-CELLS; MICE; RESISTANCE; DEGRADATION; INHIBITION; PROTEASES AB Cysteine proteases play an important part in human pathobiology(1). This report shows the participation of cathepsin L (CatL) in adipogenesis and glucose intolerance. In vitro studies demonstrate the role of CatL in the degradation of the matrix protein fibronectin, insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R), essential molecules for adipogenesis and glucose metabolism(2-5). CatL inhibition leads to the reduction of human and murine pre-adipocyte adipogenesis or lipid accumulation, protection of fibronectin from degradation, accumulation of IR and IGF-1R beta-subunits, and an increase in glucose uptake. CatL-deficient mice are lean and have reduced levels of serum glucose and insulin but increased levels of muscle IR beta-subunits, fibronectin and glucose transporter (Glut)-4, although food/water intake and energy expenditure of these mice are no less than their wildtype littermates. Importantly, the pharmacological inhibition of CatL also demonstrates reduced body weight gain and serum insulin levels, and increased glucose tolerance, probably due to increased levels of muscle IR beta-subunits, fibronectin and Glut-4 in both diet-induced obese mice and ob/ob mice. Increased levels of CatL in obese and diabetic patients suggest that this protease is a novel target for these metabolic disorders. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Med Sch, Boston, MA 02115 USA. Nanfang Hosp, Dept Rheumatol, Guangzhou 510515, Peoples R China. Nanfang Med Univ, Guangzhou 510515, Peoples R China. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Tokushima Bunri Univ, Inst Hlth Sci, Tokushima 7708514, Japan. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. INSERM, U872, F-75006 Paris, France. Univ Paris 06, Ctr Rech Cordeliers, UMRS 872, F-75006 Paris, France. Univ Paris 05, UMRS 872, F-75006 Paris, France. Hop La Pitie Salpetriere, AP HP, Nutr Dept, F-75013 Paris, France. RP Shi, GP (reprint author), Brigham & Womens Hosp, Boston, MA 02115 USA. EM gshi@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL60942, HL073168] NR 29 TC 70 Z9 72 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2007 VL 9 IS 8 BP 970 EP U130 PG 14 WC Cell Biology SC Cell Biology GA 196MM UT WOS:000248486700019 PM 17643114 ER PT J AU Welt, CK AF Welt, Corrine K. TI Will leptin become the treatment of choice for functional hypothalamic amenorrhea? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID WOMEN; DEFICIENCY; WEIGHT C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 NR 10 TC 6 Z9 6 U1 0 U2 0 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 AUG PY 2007 VL 3 IS 8 BP 556 EP 557 DI 10.1038/ncpendmet0561 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192RQ UT WOS:000248220400003 PM 17593916 ER PT J AU Kantarci, S Al-Gazali, L Hill, RS Donnai, D Black, GCM Bieth, E Chassaing, N Lacombe, D Devriendt, K Teebi, A Loscertales, M Robson, C Liu, TM MacLaughlin, DT Noonan, KM Russell, MK AWalsh, C Donahoe, PK Pober, BR AF Kantarci, Sibel Al-Gazali, Lihadh Hill, R. Sean Donnai, Dian Black, Graeme C. M. Bieth, Eric Chassaing, Nicolas Lacombe, Didier Devriendt, Koen Teebi, Ahmad Loscertales, Maria Robson, Caroline Liu, Tianming MacLaughlin, David T. Noonan, Kristin M. Russell, Meaghan K. AWalsh, Christopher Donahoe, Patricia K. Pober, Barbara R. TI Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes SO NATURE GENETICS LA English DT Article ID DIAPHRAGMATIC-HERNIA; SONIC HEDGEHOG; ANIMAL-MODEL; DEAFNESS; MICE; HYPERTELORISM; PROTEINURIA; HYPOPLASIA; RETINOL; MYOPIA AB Donnai-Barrow syndrome is associated with agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. By studying multiplex families, we mapped this disorder to chromosome 2q23.3-31.1 and identified LRP2 mutations in six families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome. LRP2 encodes megalin, a multiligand uptake receptor that regulates levels of diverse circulating compounds. This work implicates a pathway with potential pharmacological therapeutic targets. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Pediat, Al Ain, U Arab Emirates. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Univ Manchester, St Marys Hosp, Unit Med Genet, Manchester M13 0JH, Lancs, England. Hop Purpan, F-31059 Toulouse 9, France. CHU Pellegrin, Bordeaux, France. CHU Bordeaux, Hop Pellegrin, Gen Med Serv, Bordeaux, France. Catholic Univ Louvain, Ctr Human Genet, B-3000 Louvain, Belgium. Weill Cornell Med Coll, Dept Pediat, Doha, Qatar. Weill Cornell Med Coll, Dept Med Genet, Doha, Qatar. Hamad Med City, Doha, Qatar. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Ctr Neurodegenerat & Repair, Ctr Bioinformat, Boston, MA 02115 USA. MassGen Hosp Children, Boston, MA 02114 USA. RP Pober, BR (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM bpober@partners.org RI Liu, Tianming/A-2512-2008; Congregado, Miguel/B-9062-2009; OI Congregado, Miguel/0000-0002-2404-0176; Robson, Caroline/0000-0001-5592-249X; Black, Graeme/0000-0001-8727-6592 FU NICHD NIH HHS [R01 HD055150, R01 HD055150-02, R01 HD55150-01]; NINDS NIH HHS [R37 NS035129, R37 NS35129]; Wellcome Trust NR 15 TC 131 Z9 134 U1 1 U2 6 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 AUG PY 2007 VL 39 IS 8 BP 957 EP 959 DI 10.1038/ng2063 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 195XX UT WOS:000248446900009 PM 17632512 ER PT J AU Kuhn, B del Monte, F Hajjar, RJ Chang, YS Lebeche, D Arab, S Keating, MT AF Kuhn, Bernhard del Monte, Federica Hajjar, Roger J. Chang, Yuh-Shin Lebeche, Djamel Arab, Shima Keating, Mark T. TI Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair SO NATURE MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; DNA-SYNTHESIS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; TRANSGENIC MICE; CELL-LINES; IN-VITRO; HEART; KINASE; MYOCYTES AB Adult mammalian hearts respond to injury with scar formation and not with cardiomyocyte proliferation, the cellular basis of regeneration. Although cardiogenic progenitor cells may maintain myocardial turnover, they do not give rise to a robust regenerative response. Here we show that extracellular periostin induced reentry of differentiated mammalian cardiomyocytes into the cell cycle. Periostin stimulated mononucleated cardiomyocytes to go through the full mitotic cell cycle. Periostin activated alpha(V), beta(1), beta(3) and beta(5) integrins located in the cardiomyocyte cell membrane. Activation of phosphatidylinositol-3-OH kinase was required for periostin-induced reentry of cardiomyocytes into the cell cycle and was sufficient for cell-cycle reentry in the absence of periostin. After myocardial infarction, periostin-induced cardiomyocyte cell-cycle reentry and mitosis were associated with improved ventricular remodeling and myocardial function, reduced fibrosis and infarct size, and increased angiogenesis. Thus, periostin and the pathway that it regulates may provide a target for innovative strategies to treat heart failure. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Kuhn, B (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM bernhard.kuhn@cardio.chboston.org; mark.keating@novartis.com FU NHLBI NIH HHS [HL057263, HL071763, HL080498, HL083156, K01 HL076659, K08 HL069842, R01 HL078691] NR 48 TC 315 Z9 332 U1 5 U2 23 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 AUG PY 2007 VL 13 IS 8 BP 962 EP 969 DI 10.1038/nm1619 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 199CU UT WOS:000248674600027 PM 17632525 ER PT J AU Kirsch, DG Dinulescu, DM Miller, JB Grimm, J Santiago, PM Young, NP Nielsen, GP Quade, BJ Chaber, CJ Schultz, CP Takeuchi, O Bronson, RT Crowley, D Korsmeyer, SJ Yoon, SS Hornicek, FJ Weissleder, R Jacks, T AF Kirsch, David G. Dinulescu, Daniela M. Miller, John B. Grimm, Jan Santiago, Philip M. Young, Nathan P. Nielsen, G. Petur Quade, Bradley J. Chaber, Christopher J. Schultz, Christian P. Takeuchi, Osamu Bronson, Roderick T. Crowley, Denise Korsmeyer, Stanley J. Yoon, Sam S. Hornicek, Francis J. Weissleder, Ralph Jacks, Tyler TI A spatially and temporally restricted mouse model of soft tissue sarcoma SO NATURE MEDICINE LA English DT Article ID ONCOGENIC K-RAS; LUNG-CANCER; IN-VIVO; TUMOR SUPPRESSION; MUTANT MICE; P53; APOPTOSIS; GENE; TUMORIGENESIS; DEFICIENCY AB Soft tissue sarcomas are mesenchymal tumors that are fatal in approximately one-third of patients. To explore mechanisms of sarcoma pathogenesis, we have generated a mouse model of soft tissue sarcoma. Intramuscular delivery of an adenovirus expressing Cre recombinase in mice with conditional mutations in Kras and Trp53 was sufficient to initiate high-grade sarcomas with myofibroblastic differentiation. Like human sarcomas, these tumors show a predilection for lung rather than lymph node metastasis. Using this model, we showed that a prototype handheld imaging device can identify residual tumor during intraoperative molecular imaging. Deletion of the Ink4a-Arf locus (Cdkn2a), but not Bak1 and Bax, could substitute for mutation of Trp53 in this model. Deletion of Bak1 and Bax, however, was able to substitute for mutation of Trp53 in the development of sinonasal adenocarcinoma. Therefore, the intrinsic pathway of apoptosis seems sufficient to mediate p53 tumor suppression in an epithelial cancer, but not in this model of soft tissue sarcoma. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Siemens Med Solut Inc, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Sch Med & Vet Med, North Grafton, MA 01536 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tjacks@mit.edu RI Grimm, Jan/B-1937-2008 FU NCI NIH HHS [K08 CA 114176, P30-CA14051, P50 CA86355, R24 CA92782, U54 CA119349] NR 30 TC 135 Z9 137 U1 1 U2 16 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 AUG PY 2007 VL 13 IS 8 BP 992 EP 997 DI 10.1038/nm1602 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 199CU UT WOS:000248674600032 PM 17676052 ER PT J AU Hideshima, T Mitsiades, C Tonon, G Richardson, PG Anderson, KC AF Hideshima, Teru Mitsiades, Constantine Tonon, Giovanni Richardson, Paul G. Anderson, Kenneth C. TI Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets SO NATURE REVIEWS CANCER LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; MEDIATED DRUG-RESISTANCE; NF-KAPPA-B; PROTEASOME INHIBITOR BORTEZOMIB; HISTONE DEACETYLASE INHIBITION; STEM-CELL TRANSPLANTATION; CYCLIN-D DYSREGULATION; IN-SITU HYBRIDIZATION; HIGH-RISK MYELOMA; CLINICAL-IMPLICATIONS AB Multiple myeloma is a plasma cell malignancy characterized by complex heterogeneous cytogenetic abnormalities. The bone marrow microenvironment promotes multiple myeloma cell growth and resistance to conventional therapies. Although multiple myeloma remains incurable, novel targeted agents, used alone or in combination, have shown great promise to overcome conventional drug resistance and improve patient outcome. Recent oncogenomic studies have further advanced our understanding of the molecular pathogenesis of multiple myeloma, providing the framework for new prognostic classification and identifying new therapeutic targets. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 188 TC 437 Z9 454 U1 4 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2007 VL 7 IS 8 BP 585 EP 598 DI 10.1038/nrc2189 PG 14 WC Oncology SC Oncology GA 195DZ UT WOS:000248394000012 PM 17646864 ER PT J AU Pageau, GJ Hall, LL Ganesan, S Livingston, DM Lawrence, JB AF Pageau, Gayle J. Hall, Lisa L. Ganesan, Shridar Livingston, David M. Lawrence, Jeanne B. TI The disappearing Barr body in breast and ovarian cancers SO NATURE REVIEWS CANCER LA English DT Article ID INACTIVE X-CHROMOSOME; MOUSE XIST GENE; DOSAGE COMPENSATION; ESTROGEN-RECEPTOR; DNA METHYLATION; BRCA1; RNA; HETEROCHROMATIN; CELLS; EXPRESSION AB Interest has recently reawakened in whether loss of the heterochromatic X chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and new insights into the mechanisms involved have emerged. Mitotic segregation errors commonly explain the loss of the inactive X chromosome (Xi), but compromise of Xi heterochromatin in some cancers may signal broader deficits of nuclear heterochromatin. The debated link between BRCA1 and Xi might reflect a general relationship between BRCA1 and heterochromatin, which could connect BRCA1 to both epigenetic and genetic instability. We suggest that heterochromatic instability is a common but largely unexplored mechanism, leading to widespread genomic misregulation and the evolution of some cancers. C1 Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Inst Canc, Dept Med, New Brunswick, NJ 08093 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. EM david_livingston@dfci.harvard.edu; Jeanne.Lawrence@umassmed.edu OI Pouliot, Gayle/0000-0001-9730-143X FU NIGMS NIH HHS [R01 GM053234] NR 61 TC 43 Z9 45 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2007 VL 7 IS 8 BP 628 EP 633 DI 10.1038/nrc2172 PG 6 WC Oncology SC Oncology GA 195DZ UT WOS:000248394000016 PM 17611545 ER PT J AU Mathis, D Benoist, C AF Mathis, Diane Benoist, Christophe TI A decade of AIRE SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID CANDIDIASIS-ECTODERMAL DYSTROPHY; AUTOIMMUNE REGULATOR PROTEIN; POLYGLANDULAR SYNDROME TYPE-1; THYMIC EPITHELIAL-CELLS; DISEASE TYPE-I; T-CELLS; NEGATIVE SELECTION; DEFICIENT MICE; TRANSCRIPTION FACTOR; CENTRAL TOLERANCE AB In 1997, the autoimmune regulator (AIRE) gene was identified as the locus underlying susceptibility to the polyendocrine autoimmune disease known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). In the intervening 10 years, it has become increasingly clear that this rare disorder has provided us with an illuminative window on one of the most fundamental processes of the immune system - the establishment and maintenance of self tolerance. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Immunol & Immunogenet,Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Immunol & Immunogenet,Joslin Diabet Ctr, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK59658] NR 55 TC 117 Z9 128 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD AUG PY 2007 VL 7 IS 8 BP 645 EP 650 DI 10.1038/nri2136 PG 6 WC Immunology SC Immunology GA 195EA UT WOS:000248394100016 PM 17641664 ER PT J AU Jain, RK Di Tomaso, E Duda, DG Loeffler, JS Sorensen, AG Batchelor, TT AF Jain, Rakesh K. Di Tomaso, Emmanuelle Duda, Dan G. Loeffler, Jay S. Sorensen, A. Gregory Batchelor, Tracy T. TI Angiogenesis in brain tumours SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RECURRENT MALIGNANT GLIOMA; BLOOD-VESSEL FORMATION; CELL LUNG-CANCER; PHASE-I TRIAL; ANTIANGIOGENIC THERAPY; VASCULAR-PERMEABILITY; RECTAL-CANCER; SOLID TUMORS; BONE-MARROW AB Despite aggressive surgery, radiotherapy and chemotherapy, malignant gliomas remain uniformly fatal. To progress, these tumours stimulate the formation of new blood vessels through processes driven primarily by vascular endothelial growth factor (VEGF). However, the resulting vessels are structurally and functionally abnormal, and contribute to a hostile microenvironment (low oxygen tension and high interstitial fluid pressure) that selects for a more malignant phenotype with increased morbidity and mortality. Emerging preclinical and clinical data indicate that anti-VEGF therapies are potentially effective in glioblastoma-the most frequent primary brain tumour- and can transiently normalize tumour vessels. This creates a window of opportunity for optimally combining chemotherapeutics and radiation. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI leng, xianwei/F-9073-2011 NR 150 TC 590 Z9 605 U1 10 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD AUG PY 2007 VL 8 IS 8 BP 610 EP 622 DI 10.1038/nrn2175 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 192OO UT WOS:000248211800015 PM 17643088 ER PT J AU Sanchez-Pernaute, R Jenkins, BG Choi, JK Chen, YCI Isacson, O AF Sanchez-Pernaute, Rosario Jenkins, Bruce G. Choi, Ji-Kyung Chen, Yin-Ching Iris Isacson, Ole TI In vivo evidence of D-3 dopamine receptor sensitization in parkinsonian primates and rodents with L-DOPA-induced dyskinesias SO NEUROBIOLOGY OF DISEASE LA English DT Article DE dyskinesia; Parkinson's disease; dopamine; dopamine receptor; D-3; striatum; phMR1; primate ID LEVODOPA-INDUCED DYSKINESIA; 6-HYDROXYDOPAMINE-TREATED RATS; EXTRACELLULAR DOPAMINE; ACID DECARBOXYLASE; MESSENGER-RNA; BASAL GANGLIA; DISEASE; BRAIN; EXPRESSION; STRIATUM AB A growing body of evidence indicates a role for D-3 receptors in L-DOPA-induced dyskinesias. This involvement could be amenable to non-invasive in viva analysis using functional neuroimaging. With this goal, we examined the hemodynamic response to the dopamine D-3-preferring agonist 7-hydroxy-NN-di-n-propyl-2 aminotetralin (7-OHDPAT) in naive, parkinsonian and L-DOPA-treated, dyskinetic rodents and primates using pharmacological MRI (phMRI) and relative cerebral blood volume (rCBV) mapping. Administration of 7-OHDPAT induced minor negative changes of rCBV in the basal ganglia in naive and parkinsonian animals. Remarkably, the hemodynamic response was reversed (increased rCBV) in the striatum of parkinsonian animals rendered dyskinetic by repeated L-DOPA treatment. Such increase in rCBV is consistent with D, receptor-like signaling occurring in response to D3 stimulation, demonstrates a dysregulation of dopamine receptor function in dyskinesia and provides a potentially novel means for the characterization and treatment of L-DOPA-induced dyskinesia in patients. (c) 2007 Elsevier Inc. All rights reserved. C1 McLean Hosp, Neurogenerat Labs, Belmont, MA 02478 USA. Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MGH NMR Ctr, Boston, MA 02115 USA. RP Sanchez-Pernaute, R (reprint author), McLean Hosp, Neurogenerat Labs, MRC 130,115 Mill St, Belmont, MA 02478 USA. EM rpernaute@hms.harvard.edu FU NCRR NIH HHS [P51 RR000168, P51 RR000168-466888, P51RR00168]; NIDA NIH HHS [R01 DA016187]; NINDS NIH HHS [P50 NS039793-08, P50 NS039793-07, P50 NS-39793, P50 NS039793] NR 44 TC 29 Z9 29 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2007 VL 27 IS 2 BP 220 EP 227 DI 10.1016/j.nbd.2007.04.016 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 197VK UT WOS:000248584400010 PM 17588764 ER PT J AU Blagoev, KB Mihaila, B Travis, BJ Alexandrov, LB Bishop, AR Ranken, D Posse, S Gasparovic, C Mayer, A Aine, CJ Ulbert, I Morita, M Muller, W Connor, J Halgren, E AF Blagoev, K. B. Mihaila, B. Travis, B. J. Alexandrov, L. B. Bishop, A. R. Ranken, D. Posse, S. Gasparovic, C. Mayer, A. Aine, C. J. Ulbert, I. Morita, M. Muller, W. Connor, J. Halgren, E. TI Modelling the magnetic signature of neuronal tissue SO NEUROIMAGE LA English DT Article DE modelling; neural currents; MRI; MEG; neuroelectrophysiology ID MRI DETECTION; ASSOCIATION CORTEX; CEREBRAL-CORTEX; HUMAN BRAIN; IN-VIVO; CURRENTS; FIELD; POTENTIALS; SLICES; MAGNETOENCEPHALOGRAPHY AB Neuronal communication in the brain involves electrochemical currents, which produce magnetic fields. Stimulus-evoked brain responses lead to changes in these fields and can be studied using magneto- and electro-encephalography (MEG/EEG). In this paper we model the spatiotemporal distribution of the magnetic field of a physiologically idealized but anatomically realistic neuron to assess the possibility of using magnetic resonance imaging (MRI) for directly mapping the neuronal currents in the human brain. Our results show that the magnetic field several centimeters from the centre of the neuron is well approximated by a dipole source, but the field close to the neuron is not, a finding particularly important for understanding the possible contrast mechanism underlying the use of MRI to detect and locate these currents. We discuss the importance of the spatiotemporal characteristics of the magnetic field in cortical tissue for evaluating and optimizing an experiment based on this mechanism and establish an upper bound for the expected MRI signal change due to stimulus-induced cortical response. Our simulations show that the expected change of the signal magnitude is 1.6% and its phase shift is 1 degrees. An unexpected finding of this work is that the cortical orientation with respect to the external magnetic field has little effect on the predicted MRI contrast. This encouraging result shows that magnetic resonance contrast directly based on the neuronal currents present in the cortex is theoretically a feasible imaging technique. MRI contrast generation based on neuronal currents depends on the dendritic architecture and we obtained high-resolution optical images of cortical tissue to discuss the spatial structure of the magnetic field in grey matter. Published by Elsevier Inc. C1 Los Alamos Natl Lab, Theoret Div, Los Alamos, NM 87544 USA. MIND Inst, Albuquerque, NM 87131 USA. Los Alamos Natl Lab, Earth & Environm Sci Div, Los Alamos, NM 87544 USA. Los Alamos Natl Lab, Commun & Comp Network Div, Los Alamos, NM 87544 USA. Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, MGN NMR Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA 02169 USA. Univ New Mexico, Dept Neurosurg, Albuquerque, NM 87131 USA. Univ New Mexico, Brain Imaging Ctr, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP Blagoev, KB (reprint author), Los Alamos Natl Lab, Theoret Div, Los Alamos, NM 87544 USA. EM krastan@lanl.gov RI Ulbert, Istvan/F-2213-2010; Gasparovic, Charles/E-7289-2010; Mihaila, Bogdan/D-8795-2013; Alexandrov, Ludmil/B-6582-2014 OI Mihaila, Bogdan/0000-0002-1489-8814; Alexandrov, Ludmil/0000-0003-3596-4515 FU NINDS NIH HHS [NS44623, R01 NS044623] NR 42 TC 31 Z9 31 U1 0 U2 8 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 AUG 1 PY 2007 VL 37 IS 1 BP 137 EP 148 DI 10.1016/j.neuroimage.2007.04.033 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 197AY UT WOS:000248526700014 PM 17544300 ER PT J AU Dabus, G Moran, CJ Derdeyn, CP Cross, DT AF Dabus, Guilherme Moran, Christopher J. Derdeyn, Colin P. Cross, DeWitte T., III TI Endovascular treatment of vertebral artery-origin and innominate/subclavian disease: Indications and technique SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; POSTERIOR CIRCULATION REGISTRY; INNOMINATE-ARTERY; SUBCLAVIAN ARTERY; STENT PLACEMENT; ATHEROSCLEROTIC DISEASE; FOLLOW-UP; STENOSIS; RESTENOSIS; HYPERPLASIA AB Approximately 20% to 40% of patients who have cerebral vascular disease have a vertebral artery-origin stenosis. Atherosclerotic lesions of vertebral arety origin are a potential cause of posterior circulation ischemia, which can be disabling or deadly. Endovascular treatment of vertebral artery-origin and innominate/subclavian artery stenosis has changed in the last 15 years. Surgery usually is successful technically; however, it is also associated with high rates of procedural and periprocedural complications. New techniques and technologies that can be used in the treatment of such lesions are being developed. in this article, the authors discuss the indications, technical aspects, and long-term results of angioplasty and stenting of these vessels. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol, Boston, MA 02114 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Div Intervent Neuroradiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Dabus, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol, Gray 241,55 Fruit St, Boston, MA 02114 USA. EM gdabus@partners.org OI Derdeyn, Colin/0000-0002-5932-2683 NR 38 TC 5 Z9 10 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2007 VL 17 IS 3 BP 381 EP + DI 10.1016/j.nic.2007.03.005 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 217IM UT WOS:000249941600010 PM 17826639 ER PT J AU Nahas, Z Teneback, C Chae, JH Mu, QW Molnar, C Kozel, FA Walker, J Anderson, B Koola, J Kose, S Lomarev, M Bohning, DE George, MS AF Nahas, Ziad Teneback, Charlotte Chae, Jeong-Ho Mu, Qiwen Molnar, Chris Kozel, Frank A. Walker, John Anderson, Berry Koola, Jejo Kose, Samet Lomarev, Mikhail Bohning, Daryl E. George, Mark S. TI Serial vagus nerve stimulation functional MRI in treatment-resistant depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiat, Amer Coll Neuropsychopharmacol DE vagus nerve stimulation; fMRI; depression; antidepressant ID TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL-BLOOD-FLOW; MAJOR DEPRESSION; SLEEP-DEPRIVATION; PREFRONTAL CORTEX; BRAIN METABOLISM; PARTIAL EPILEPSY; BOLD FMRI; ANTIDEPRESSANT RESPONSE; GLUCOSE-METABOLISM AB Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, doubleblind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS. C1 Inst Psychiat, Mood Disorders Program, Brain Stimulat Lab, Dept Psychiat, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Catholic Univ, Dept Psychiat, Seoul, South Korea. NINDS, Bethesda, MD 20892 USA. Ralph H Johson VA Med Ctr, Dept Psychiat, Charleston, SC USA. RP Nahas, Z (reprint author), Inst Psychiat, Mood Disorders Program, Brain Stimulat Lab, Dept Psychiat, 67 President St,Room 502 N, Charleston, SC 29403 USA. EM nahasz@musc.edu RI Kozel, Frank/I-5366-2012 FU NIMH NIH HHS [MH070615-01A1, R01 MH069896-01, R21 MH065630-01]; NINDS NIH HHS [R01 NS40956-01] NR 67 TC 57 Z9 59 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2007 VL 32 IS 8 BP 1649 EP 1660 DI 10.1038/sj.npp.1301288 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 191QU UT WOS:000248146900001 PM 17203016 ER PT J AU Flanz, JB AF Flanz, Jacob B. TI What's new in particle therapy accelerator technology SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 19th International Conference on Application of Accelerators in Research and Industry CY AUG 20-25, 2006 CL Ft Worth, TX SP Lawrence Berkeley Natl Lab, Lawrence Livemore Natl Lab, Los Alamos Natl Lab, Natl Canc Inst, Oak Ridge Associated Univ, Oak Ridge Natl Lab, Sandia Natl Lab, Univ N Texas, AccSys Technol Inc, Comecer SRL, Natl Electrostat Corp, Synergy Vacuum DE particle therapy; accelerators; beam delivery systems; medical physics AB Recently, particle therapy has entered a new age. The number of facilities opening and under construction is at an all time high. We are now at an interesting time in the cycle of product development and 'consumer' interest, where; on the one hand, the interest in the technique has encouraged some groups who are working on new ideas; but on the other hand, existing product production, to reduce costs and improve procurement, installation and commissioning time tends to reduce the degree of change that can be considered in a system. This paper summarizes some of the current requirements and directions in particle therapy accelerator technology. (c) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Med Ctr, Burr Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. RP Flanz, JB (reprint author), Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. EM flanz@hadron.mgh.harvard.edu NR 8 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD AUG PY 2007 VL 261 IS 1-2 BP 768 EP 772 DI 10.1016/j.nimb.2007.04.247 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 200SW UT WOS:000248784100184 ER PT J AU Sisterson, JM AF Sisterson, Janet M. TI Cross section measurements for neutron-induced reactions off C, Al, SiO2, Si and Au producing relatively short-lived radionuclides at neutron energies between 70 and 160 MeV SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 19th International Conference on Application of Accelerators in Research and Industry CY AUG 20-25, 2006 CL Ft Worth, TX SP Lawrence Berkeley Natl Lab, Lawrence Livemore Natl Lab, Los Alamos Natl Lab, Natl Canc Inst, Oak Ridge Associated Univ, Oak Ridge Natl Lab, Sandia Natl Lab, Univ N Texas, AccSys Technol Inc, Comecer SRL, Natl Electrostat Corp, Synergy Vacuum DE spallation reactions; neutron beams; cross section measurements AB A systematic study was made to measure many cross sections for relevant neutron-induced reactions. This study was motivated by the need to better understand cosmic ray interactions with extraterrestrial materials. The major constituents of meteorites and lunar rocks include oxygen, silicon, and aluminum. The primary aim was to measure cross sections for neutron-induced reactions producing long-lived radionuclides (e.g. C-14) and stable isotopes (e.g. Ne isotopes) but the irradiation conditions allowed cross sections for many reactions producing relatively short-lived radionuclides (e. g. Na-22) to be well measured. Monitor foils used in the irradiations included C, Al, and Au. Quasi-monoenergetic neutron beams were produced by bombarding Be targets with 80, 120 and 160 MeV proton beams at iThe-mba LABS, South Africa. Two identical target stacks were irradiated in beam lines at 0 degrees and 16 degrees to the incident proton beam direction. The yield at an unique neutron energy was obtained by subtracting the yield measured at 16 degrees (after suitable normalization) from that measured at 0 degrees. The cross sections for the following reactions: Al-27(n, x)Na-22,Na-24; C-nat(n,x)Be-7; Au-197(n,x)(194,196) Au; SiO2(n, x)Na-22 and Si-nat(n, x)Na-24 are reported. (c) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Sisterson, JM (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM jsisterson@partners.org NR 10 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD AUG PY 2007 VL 261 IS 1-2 BP 993 EP 995 DI 10.1016/j.nimb.2007.03.030 PG 3 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 200SW UT WOS:000248784100237 ER PT J AU Imam, SZ Indig, FE Cheng, WH Saxena, SP Stevnsner, T Kufe, D Bohr, VA AF Imam, Syed Z. Indig, Fred E. Cheng, Wen-Hsing Saxena, Satya P. Stevnsner, Tinna Kufe, Donald Bohr, Vilhelm A. TI Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-DAMAGE; OXIDATIVE STRESS; APOPTOTIC RESPONSE; INDUCE APOPTOSIS; CELLULAR REPAIR; EXCISION-REPAIR; ACTIVE GENES; 8-HYDROXYADENINE; 8-HYDROXYGUANINE; ACTIVATION AB The Cockayne Syndrome group B (CSB) protein plays important roles in transcription, transcription-coupled nucleotide excision repair and base excision DNA repair. c-Abl kinase also plays a role in DNA repair as a regulator/coordinator of the DNA damage response. This study presents evidence that the N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. The subcellular localization of CSB to the nucleus and nucleolus is altered after phosphorylation by c-Abl. c-Abl-dependent phosphorylation of CSB increased in cells treated with hydrogen peroxide and decreased in cells pre-treated with STI-571, a c-Abl-specific protein kinase inhibitor. Activation of the c-Abl kinase in response to oxidative damage is not observed in CSB null cells. These results suggest that c-Abl and CSB may regulate each other in a reciprocal manner in response to oxidative stress. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NIA, Res Resource Branch, NIH, Baltimore, MD 21224 USA. Univ Aarhus, MBI, Danish Ctr Mol Gerontol, DK-8000 Aarhus, Denmark. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural NIH HHS NR 39 TC 13 Z9 16 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG PY 2007 VL 35 IS 15 BP 4941 EP 4951 DI 10.1093/nar/gkm386 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212QQ UT WOS:000249612300002 PM 17626041 ER PT J AU Schiff, I AF Schiff, Isaac TI The pill and the pendulum SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID ESTROGEN PLUS PROGESTIN; ENDOMETRIAL CARCINOMA; POSTMENOPAUSAL WOMEN; HORMONE-THERAPY; DISEASE; TRIAL; RISK C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Schiff, I (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. EM ischiff@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2007 VL 110 IS 2 BP 228 EP 229 DI 10.1097/01.AOG.0000277651.58940.fa PN 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 193QY UT WOS:000248290500002 PM 17666594 ER PT J AU Willett, CG Duda, DG Czito, BG Bendell, JC Clark, JW Jain, RK AF Willett, Christopher G. Duda, Dan G. Czito, Brian G. Bendell, Johanna C. Clark, Jeffrey W. Jain, Rakesh K. TI Targeted therapy in rectal cancer SO ONCOLOGY-NEW YORK LA English DT Article ID GROWTH-FACTOR-RECEPTOR; PHASE-I TRIAL; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITOR; TOTAL MESORECTAL EXCISION; PREOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; VASCULAR NORMALIZATION; ANTIANGIOGENIC THERAPY; COMBINATION THERAPY AB Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of-cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer. C1 [Willett, Christopher G.; Czito, Brian G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27705 USA. [Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bendell, Johanna C.] Duke Univ, Med Ctr, Div Transplantat & Oncol, Durham, NC USA. [Clark, Jeffrey W.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. RP Willett, CG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27705 USA. EM christopher.willett@duke.edu OI Duda, Dan G./0000-0001-7065-8797 FU NCI NIH HHS [P01 CA080124, R21 CA099237, R21 CA099237-02, P01 CA080124-08] NR 62 TC 17 Z9 17 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD AUG PY 2007 VL 21 IS 9 BP 1055 EP 1065 PG 11 WC Oncology SC Oncology GA 270RP UT WOS:000253738200003 PM 17910311 ER PT J AU Perner, S Mertz, KD Kufer, R Rubin, MA AF Perner, S. Mertz, K. D. Kuefer, R. Rubin, M. A. TI Biomarkers for prostate cancer. Molecular approaches to assess prognosis SO ONKOLOGE LA German DT Article DE prostate cancer; biomarkers; PSA; diagnosis in the early stages; genomics and proteomics ID STEM-CELL ANTIGEN; MEMBRANE ANTIGEN; EXPRESSION; HETEROGENEITY; PROGRESSION; RACEMASE; HETEROZYGOSITY; RECURRENCE; TMPRSS2; FUSION AB Although prostate-specific antigen (PSA) has been shown to be an auxiliary instrument in the management of prostate cancer, there is still an urgent need for better biomarkers. More sensitive and specific biomarkers are needed for a more precise and accurate diagnosis in the early stages of the disease. Furthermore, biomarkers are required for prognostic and predictive purposes. Recent advances in the field of genomics and proteomics have resulted in the identification of promising biomarkers for prostate cancer. This article reviews and discusses several of the most promising candidate biomarkers for prostate cancer. C1 [Perner, S.; Mertz, K. D.; Rubin, M. A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Perner, S.] Univ Ulm Klinikum, Abt Pathol, Ulm, Germany. [Kuefer, R.] Univ Ulm Klinikum, Urol Univ Klin, Ulm, Germany. [Kuefer, R.] Ctr Comprehens Canc, Ulm, Germany. [Rubin, M. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rubin, M. A.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Rubin, M. A.] MIT, Cambridge, MA 02139 USA. RP Rubin, MA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave,EBRC 442A, Boston, MA 02115 USA. EM marubin@partners.org NR 30 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0947-8965 J9 ONKOLOGE JI Onkologe PD AUG PY 2007 VL 13 IS 8 BP 669 EP + DI 10.1007/s00761-007-1225-9 PG 7 WC Oncology SC Oncology GA 281SO UT WOS:000254519400002 ER PT J AU Morales, TI AF Morales, T. I. TI Chondrocyte moves: clever strategies? SO OSTEOARTHRITIS AND CARTILAGE LA English DT Review DE chondrocyte; cartilage; movement; migration; cell process ID HUMAN ARTICULAR-CARTILAGE; SMOOTH MUSCLE ACTIN; LONGITUDINAL BONE-GROWTH; PRIMARY MAMMARY-TUMORS; CELL-MIGRATION; PLASMINOGEN-ACTIVATOR; INTERVERTEBRAL DISC; GENE-EXPRESSION; MATRIX-METALLOPROTEINASE; UROKINASE RECEPTOR AB Goals: To review the literature on chondrocyte movements and to develop plausible hypothesis for further work Design: Chondrocyte movements are herein defined as translocations of the cell body. A brief overview of cell migration in other cell types is presented to set the stage for a discussion of chondrocyte moves; this includes a discussion of the challenges that cells find when moving within tissues. Reports of isolated chondrocyte migration in vitro (isolated cell systems) and ex vivo (cartilage organ cultures) are then summarized, followed by a discussion of recent studies that infer chondrocyte movements in vivo. Results: Investigators from different laboratories have observed chondrocyte motility in vitro. I became interested in the question of whether 49 articular chondrocytes retained their phenotype during their migratory excursions. We devised a simple method to separate migratory and stationary chondrocytes and then showed that migratory chondrocytes synthesized collagen II but not I - consistent with a differentiated phenotype. Our time-lapse video microscopy studies showed that the cells displayed appropriate movement kinetics, albeit with low speed and directionality. Similarly, others have presented data consistent with slow movement of chondrocytes out of cartilage explants. It is important to decipher whether these in vitro movements reflect physiological states and if so, which events are simulated. Examples of in vivo studies that have inferred chondrocyte movements include those describing rotational or gliding movements of chondrocytes in the proliferative zone of the growth plate and its importance in the growth process; and the notion that chondrocytes move from the cartilage endplates to the nucleus pulposus (NP) in the spine of rabbits and rats during development. Such studies are consistent with the hypothesis that chondrocytes exhibit highly controlled and specialized movements during tissue growth and remodeling in vivo. On the other hand, the cartilage explant studies elicit interest in the possibility that matrix injuries resulting in disruption of the collagen network of adult cartilages provide a permissive environment for chondrocyte motility. Conclusions: The case for in vivo chondrocyte motility remains to be proven. However, the in vitro and in vivo data on chondrocyte movements present an argument for further thought and studies in this area. (c) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Morales, TI (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Jackson 1223,55 Fruit St, Boston, MA 02114 USA. EM tmorales@partners.org FU NIAMS NIH HHS [R21 AR047000-01, R21 AR047000-02, R21 AR047000-03] NR 77 TC 56 Z9 56 U1 4 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD AUG PY 2007 VL 15 IS 8 BP 861 EP 871 DI 10.1016/j.joca.2007.02.022 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 207SV UT WOS:000249272300003 PM 17467303 ER PT J AU Li, PMMC Wang, HB Northrop, C Merchant, SN Nadol, JB AF Li, Peter M. M. C. Wang, Haobing Northrop, Clarinda Merchant, Saurnil N. Nadol, Joseph B., Jr. TI Anatomy of the round window and hook region of the cochlea with implications for cochlear implantation and other endocochlear surgical procedures SO OTOLOGY & NEUROTOLOGY LA English DT Article DE cochlear implants; cochlear implantation; round window; three-dimensional imaging; computer generated; surgical procedures; temporal bone; histology ID ELECTRIC ACOUSTIC STIMULATION; HUMAN TEMPORAL BONES; HEARING PRESERVATION; INSERTION; TRAUMA; HISTOPATHOLOGY; ARRAY AB Hypothesis: The goal of this study was to create a three-dimensional model of the anatomy of the hook region to identify the optimal site for cochleostomy in cochlear implant surgery. Background: The anatomy of the hook region is complex, and spatial relationships can be difficult to evaluate using two-dimensional histological slides or cadaveric temporal bones. Methods: The right temporal bone of a 14-year-old adolescent boy was used to create a three-dimensional model. Sections containing the round window membrane (RWM) and surrounding cochlear structures were stained, digitized, and imported into a general purpose three-dimensional rendering and analysis software program (Amira, version 4.1). Three-dimensional models of the RWM, basilar membrane, osseous spiral lamina, spiral ligament, cochlear aqueduct, inferior cochlea vein, scala media, ductus reuniens, scala vestibuli, scala tympani, and surrounding bone were generated. The relationship between these structures and the RWM and adjacentotic capsule was evaluated. Histological sections from a different temporal bone were also analyzed. This temporal bone was sectioned in a plane perpendicular to the axis corresponding to the surgical view of the RWM, seen through the facial recess. Results: The anteroinferior margin of the RWM or adjacent otic capsule was identified as the site for a cochleostomy that will avoid damage to critical cochlear structures and allow implantation directly into the scala tympani. The model can be downloaded from: https://research.meei.harvard.edu/otopatliology/3dmodels. Conclusion: This three-dimensional model has implications for surgical procedures to the inner ear that aim to minimize insertional trauma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. EM Joseph_nadol@meei.harvard.edu FU NIDCD NIH HHS [1U24DC008559, 5 R01DC00152, P30 DC005209, P30 DC05209, R01 DC000152, U24 DC008559, U24 DC008559-01] NR 28 TC 45 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD AUG PY 2007 VL 28 IS 5 BP 641 EP 648 DI 10.1097/mao.0b013e3180577949 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 197LY UT WOS:000248558300009 PM 17667773 ER PT J AU Tournoux, FB Manzke, R Chan, RC Solis, J Chen-Tournoux, AA Gerard, O Nandigam, V Allain, P Reddy, V Ruskin, JN Weyman, AE Picard, MH Singh, JP AF Tournoux, Francois B. Manzke, Robert Chan, Raymond C. Solis, Jorge Chen-Tournoux, Annabel A. Gerard, Olivier Nandigam, Veena Allain, Pascal Reddy, Vivek Ruskin, Jeremy N. Weyman, Arthur E. Picard, Michael H. Singh, Jagmeet P. TI Integrating functional and anatomical information to facilitate cardiac resynchronization therapy SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE CRT; congestive heart failure; computing; echocardiography; new technology AB Multiple imaging modalities are required in patients receiving cardiac resynchronization therapy. We have developed a strategy to integrate echocardiographic and angiographic information to facilitate left ventricle (LV) lead position. Full three-dimensional LV-volumes (3DLVV) and dyssynchrony maps were acquired before and after resynchronization. At the time of device implantation, 3D-rotational coronary venous angiography was performed. 3D-models of the veins were then integrated with the pre- and post-3DLVV In the case displayed, prior to implantation, the lateral wall was delayed compared to the septum. The LV lead was positioned into the vein over the most delayed region, resulting in improved LV synchrony. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab,Cardiol Div, Boston, MA 02114 USA. Philips Res N Amer, Clin Sites Res Program, Boston, MA USA. Philips Med Syst, Suresnes, France. RP Tournoux, FB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab,Cardiol Div, Blake 255,55 Fruit St, Boston, MA 02114 USA. EM ftournoux@gmail.com OI Picard, Michael/0000-0002-9264-3243 NR 0 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD AUG PY 2007 VL 30 IS 8 BP 1021 EP 1022 DI 10.1111/j.1540-8159.2007.00803.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 201AK UT WOS:000248803700015 PM 17669088 ER PT J AU Napadow, V Kettner, N Liu, J Li, M Kwong, KK Vangel, M Maki-Is, N Audette, J Hui, KKS AF Napadow, V. Kettner, N. Liu, J. Li, M. Kwong, K. K. Vangel, M. Maki-Is, N. Audette, J. Hui, K. K. S. TI Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome SO PAIN LA English DT Article DE chronic pain; limbic; brain; complementary and alternative medicine ID POSITRON-EMISSION-TOMOGRAPHY; SYMPATHETIC SKIN-RESPONSE; HUMAN BRAIN; HEALTHY-SUBJECTS; LIMBIC SYSTEM; PAIN; FMRI; ACTIVATION; ANALGESIA; CORTEX AB Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used rMRI to evaluate verum and sham acupuncture stimulation at acupoint LI-4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HQ. CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short-term brain response to acupuncture stimulation, as well as the influence of longer-term acupuncture therapy effects on this short-term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non-specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala, - the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter-digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala. (C) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. Massachusetts Gen Hosp, Dept Neurol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Spaulding Rehabil Hosp, Boston, MA USA. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM vitaly@nmr.mgh.harvard.edu FU NCCIH NIH HHS [K01 AT002166-02, K01 AT002166-01, K01 AT002166-03, K01 AT002166-04, K01-AT002166-01, P01 AT002048, P01-AT002048-02, K01 AT002166]; NCRR NIH HHS [P41 RR014075, P41RR14075] NR 57 TC 90 Z9 97 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD AUG PY 2007 VL 130 IS 3 BP 254 EP 266 DI 10.1016/j.pain.2006.12.003 PG 13 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 196QF UT WOS:000248496400009 PM 17240066 ER PT J AU Tubman, VN Bennett, CM Luo, HY Chui, DHK Heeney, MM AF Tubman, Venee N. Bennett, Carolyn M. Luo, Hong-yuan Chui, David H. K. Heeney, Matthew M. TI Sickle cell disease caused by Hb S/Quebec-CHORI: Treatment with hydroxyurea and response SO PEDIATRIC BLOOD & CANCER LA English DT Article DE abnormal hemoglobins; hemoglobin Quebec-CHORI; hydroxyurea; sickle cell anemia ID HEMOGLOBIN-S; CHILDREN; PREVENTION; EXPERIENCE; ANEMIA; TRAIT AB Sickle hemoglobin (Hb S; beta Glu6Val) is due to an A > T transversion in codon 6 of the beta-globin gene. Other variant hemoglobins mimic Hb A, S, or C on newborn screening and clinical laboratory diagnostic tools, thus making their correct identification potentially difficult. Sickling disorders can result in individuals who are compound heterozygous for beta-globin mutations (e.g., Hb SC, HbSO(Arab)). The authors report a second case of HbS/ Quebec-CHORI, a severe compound heterozygous sickling disorder and their experience managing this patient with hydroxyurea. C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Boston Med Ctr, Hemoglobin Diagnost Reference Lab, Boston, MA USA. Boston Univ, Sch Med, Ctr Excellence Sickle Cell Dis, Dept Med, Boston, MA 02215 USA. RP Heeney, MM (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, Fegan 704,300 Longwood Ave, Boston, MA 02115 USA. EM matthew.heeney@childrens.harvard.edu RI Heeney, Matthew/J-6838-2015 OI Heeney, Matthew/0000-0002-1104-6843 NR 14 TC 2 Z9 2 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD AUG PY 2007 VL 49 IS 2 BP 207 EP 210 DI 10.1002/pbc.21269 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 184BQ UT WOS:000247616500018 PM 17551985 ER PT J AU Chan, YM Laffel, LMB AF Chan, Yee-Ming Laffel, Lori M. B. TI Transition from insulin to glyburide in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11 SO PEDIATRIC DIABETES LA English DT Article DE Kir6.2 channel; neonatal diabetes mellitus; sulfonylurea compounds ID ACTIVATING MUTATIONS; SULFONYLUREA THERAPY; KIR6.2; GENE; GLIBENCLAMIDE AB Initial management of neonatal diabetes mellitus consists of; insulin and adequate calories for growth. Once a genetic diagnosis is made, most patients with neonatal diabetes caused by mutations in the KC2VJ11 gene can be successfully managed with a sulfonylurea agent without the need for insulin. We report on the transition from insulin to glyburide (glibenclamide) therapy in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11. Dosing of glyburide three times daily was critical for her successful transition. C1 Childrens Hosp Boston, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Chan, YM (reprint author), Childrens Hosp Boston, Dept Med, Div Endocrinol, 333 Longwood Ave,6th Floor, Boston, MA 02115 USA. EM yee-ming.chan@childrens.harvard.edu NR 9 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD AUG PY 2007 VL 8 IS 4 BP 235 EP 238 DI 10.1111/j.1399-5448.2007.00231.x PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 196LS UT WOS:000248483900010 PM 17659066 ER PT J AU Pomerantz, B Anupindi, S Wales, PW Doody, DP Masiakos, PT AF Pomerantz, Benjamin Anupindi, Sudha Wales, Paul W. Doody, Daniel P. Masiakos, Peter T. TI Radiographic reduction of intussusception in patients with cystic fibrosis SO PEDIATRIC SURGERY INTERNATIONAL LA English DT Article DE cystic fibrosis; intussusception; reduction ID ABDOMINAL MANIFESTATIONS AB Cystic fibrosis (CF) is a genetic disorder affecting approximately one in 2,500 births in the United States. Nearly 1% of patients with CF will develop intussusception, which is commonly ileocecal and felt to be secondary to inspissated feces. These patients generally present before the age of ten. Once the diagnosis of intussusception is confirmed on ultrasound or CT, surgery has been the mainstay of treatment in this patient group. We propose the use of air and contrast enemas as effective and beneficial non-operative approach in these patients. Clinical and imaging findings in four children with known CF who presented with intestinal intussusception, average age 13.25 +/- 5.3 years (range 8-18 years) were reviewed. Patients were diagnosed using ultrasound (n = 3) or abdominal CT (n = 1). All patients suffered from an ileocolic intussusception. Air and Gastrografin (R) enemas were used in an attempt to reduce the intussusception. There were six separate successful intussusception reductions in four patients. Three patients required multiple attempts (2.3 +/- 0.6). Air enemas were used initially in all cases. Gastrografin (R) was used successfully following the failure of air enema in one patient. One patient suffered three separate intussusceptions over a period of 18 months, which were all successfully reduced using air. There were no complications and the patients tolerated the procedure well. Intussusception is an uncommon but serious complication in children with CF. While surgical reduction has been the mainstay of treatment for these patients, we demonstrated that reduction of an intussusception using air or contrast can be accomplished safely, without anesthesia, and should be the initial treatment option. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Hosp Sick Children, Dept Pediat Surg, Toronto, ON M5G 1X8, Canada. RP Masiakos, PT (reprint author), MassGen Hosp Children, Dept Pediat Surg Serv, 55 Fruit St,WRN 1155, Boston, MA 02114 USA. EM pmasiakos@partners.org NR 9 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-0358 J9 PEDIATR SURG INT JI Pediatr. Surg. Int. PD AUG PY 2007 VL 23 IS 8 BP 763 EP 765 DI 10.1007/s00383-007-1953-3 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 192HJ UT WOS:000248191300007 PM 17594107 ER PT J AU Aarnoudse, AJLHJ Newton-Cheh, C Uitterlinden, AG Stricker, BHC AF Aarnoudse, Albert-Jan L. H. J. Newton-Cheh, Christopher Uitterlinden, Andre G. Stricker, Bruno H. Ch TI Increased QTc shortening to digoxin in common NOS1AP variants SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Insectorate Hlth Care, The Hague, Netherlands. ErasmusMC, Rotterdam, Netherlands. Massachusetts Gen Hosp, Div Carcinogenesis, Boston, MA 02114 USA. Broad Inst, Cambridge, MA USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 050 BP S24 EP S25 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200051 ER PT J AU Chen, SY Maciejewski, M Au, D AF Chen, Shih-Yin Maciejewski, Matthew Au, David TI Health and economic impacts of different approaches to disease management for adults with asthma SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. HSR&D, Durham, NC USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 360 BP S171 EP S171 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200360 ER PT J AU Cotter, D Zhang, Y Thamer, M Kaufman, J Heman, M AF Cotter, Dennis Zhang, Yi Thamer, Mae Kaufman, James Heman, Miguel TI The effect of epoetin dose on haematocrit response: Implications for health policy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Med Technol & Practice Patterns Inst, Bethesda, MD USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Healthcare Syst, Vet Affairs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 069 BP S34 EP S34 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200070 ER PT J AU Fischer, MA Ferris, TG Vogeli, C Stedrnan, M Brookhart, MA Weissman, JS AF Fischer, M. A. Ferris, T. G. Vogeli, C. Stedrnan, M. Brookhart, M. A. Weissman, J. S. TI Impact of e-prescribing on medication use and cost in community-based practices SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 068 BP S33 EP S33 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200069 ER PT J AU Hermos, J Lawler, E Young, M Gagnon, D Fiore, L AF Hermos, John Lawler, Elizabeth Young, Melissa Gagnon, David Fiore, Louis TI Proton pump inhibitor (PPI) use and pneumonia risk in veteran patients with and without co-morbidities SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 BP S231 EP S231 DI 10.1002/pds PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200485 ER PT J AU Kahler, KH Rajan, M Rhoads, GG Safford, MM Demissie, K Lu, SE Pogach, LM AF Kahler, Kristijan H. Rajan, Mangala Rhoads, George G. Safford, Monika M. Demissie, Kitaw Lu, Shou-En Pogach, Leonard M. TI Variation in diabetes drug utilization among medical facilities in the veterans health administration (VHA) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 VA New Jersey Hlth Care Syst, Ctr Hlth Care Knowledge & Management, E Orange, NJ USA. Univ Med & Dent New Jersey, Piscataway, NJ USA. Birmingham VA Med Ctr, Deep S Ctr Effect, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 008 BP S4 EP S4 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200009 ER PT J AU Lawler, EV Gagnon, DR Scranton, RE AF Lawler, Elizabeth V. Gagnon, David R. Scranton, Richard E. TI Daily medication adherence and dose changes on the effectiveness of statin therapy in LDL cholesterol change SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 MAVERIC, VA Boston Healthcare Syst, Jamaica Plain, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 087 BP S42 EP S43 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200088 ER PT J AU Setoguchi, S Mittleman, MA Levin, R Winkelmayer, WC AF Setoguchi, Soko Mittleman, Murray A. Levin, Raisa Winkelmayer, Wolfgang C. TI Improvements in long-term mortality after myocardial infarction can be explained by increased use of cardiovascular drugs after discharge: A 10-year trend analysis among the community dwelling elderly SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoecon, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 037 BP S18 EP S18 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200038 ER PT J AU Tohen, M Kryzhanovskaya, L Carlson, G DelBello, M Wozniak, J Kowatch, R Wagner, K Findling, R Lin, D Robertson-Plouch, C Xu, W Dittmann, R Biederman, J AF Tohen, Mauricio Kryzhanovskaya, Ludmila Carlson, Gabrielle DelBello, Melissa Wozniak, Janet Kowatch, Robert Wagner, Karen Findling, Robert Lin, Daniel Robertson-Plouch, Carol Xu, Wen Dittmann, Ralf Biederman, Joe TI Olanzapine in the treatment of adolescents with bipolar mania; 26-week open-label extension SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Eli Lilly & Co, Indianapolis, IN USA. McLean Hosp, Harvard Med Sch, Belmont, MA USA. SUNY Stony Brook, Sch Med, Stony Brook, NY USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Univ Texas, Med Branch, Galveston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Lilly Deutschland GmbH, Bad Homburg, Germany. Univ Hamburg, Hamburg, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 453 BP S215 EP S215 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200451 ER PT J AU Vander Stichele, RH Avorn, J Ruths, S Elseviers, MM Steinman, M Gurwitz, J AF Vander Stichele, Robert H. Avorn, Jerry Ruths, Sabine Elseviers, Monique M. Steinman, Mike Gurwitz, Jerry TI The quality of pharmaceutical care among institutionalised elderly SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Univ Ghent, Heymans Inst, B-9000 Ghent, Belgium. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol, Cambridge, MA 02138 USA. Univ Bergen, Dept Geriatr, Bergen, Norway. Univ Antwerp, B-2020 Antwerp, Belgium. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. RI Vander Stichele, Robert/K-7203-2015 OI Vander Stichele, Robert/0000-0001-9118-9651 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 160 BP S76 EP S77 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200161 ER PT J AU Narita, M Tsuji, BT Yu, VL AF Narita, Masashi Tsuji, Brian T. Yu, Victor L. TI Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome SO PHARMACOTHERAPY LA English DT Review DE linezolid; adverse effects; peripheral neuropathy; optic neuropathy; lactic acidosis; serotonin syndrome ID MITOCHONDRIAL PROTEIN-SYNTHESIS; REUPTAKE INHIBITORS; DRUG-INTERACTIONS; THERAPY; INFECTIONS AB Linezolid is an oxazolidinone antibacterial agent indicated for serious grampositive infections. Only minor adverse effects were seen in phase III trials. However, more serious adverse effects were reported after commercial release, including cases of lactic acidosis, peripheral and optic neuropathy, and serotonin syndrome. Peripheral and optic neuropathy was usually seen after several months of linezolid therapy (median 5 mo), lactic acidosis after several weeks (median 6 wks), and serotonin syndrome after several days (median 4 days). Death occurred in two of seven reported cases of lactic acidosis, and three of 15 reported cases of serotonin syndrome. Improvement or complete recovery occurred in all cases of optic neuropathy, whereas complete recovery failed to occur in any patient with peripheral neuropathy. Linezolid should be discontinued immediately in patients experiencing these adverse effects. Patients receiving linezolid for more than 28 days should be monitored for signs of peripheral and optic neuropathy C1 Univ Pittsburgh, Infect Dis Sect, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. RP Yu, VL (reprint author), VA Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. NR 38 TC 87 Z9 91 U1 2 U2 5 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2007 VL 27 IS 8 BP 1189 EP 1197 DI 10.1592/phco.27.8.1189 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 195IG UT WOS:000248405100010 PM 17655517 ER PT J AU Cho, US Morrone, S Sablina, AA Arroyo, JD Hahn, WC Xu, WQ AF Cho, Uhn Soo Morrone, Seamus Sablina, Anna A. Arroyo, Jason D. Hahn, William C. Xu, Wenqing TI Structural basis of PP2A inhibition by small t antigen SO PLOS BIOLOGY LA English DT Article ID PROTEIN PHOSPHATASE 2A; HUMAN CELL-TRANSFORMATION; SMALL TUMOR-ANTIGEN; SIMIAN VIRUS-40; SUBUNIT INTERACTION; PPP2R1B GENE; CORE ENZYME; B-SUBUNITS; ZINC IONS; A-SUBUNIT AB The SV40 small t antigen ( ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit. We have determined the crystal structure of full-length ST in complex with PP2A A subunit at 3.1 angstrom resolution. ST consists of an N-terminal J domain and a C-terminal unique domain that contains two zinc-binding motifs. Both the J domain and second zinc-binding motif interact with the intra-HEAT-repeat loops of HEAT repeats 3-7 of the A subunit, which overlaps with the binding site of the PP2A B56 subunit. Intriguingly, the first zinc-binding motif is in a position that may allow it to directly interact with and inhibit the phosphatase activity of the PP2A catalytic C subunit. These observations provide a structural basis for understanding the oncogenic functions of ST. C1 Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Broad Inst Harvard & MIT, Cambridge, MA USA. RP Xu, WQ (reprint author), Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. EM wxu@u.washington.edu OI Xu, Wenqing/0000-0002-2884-3101; Arroyo, Jason/0000-0002-5674-6739 FU NCI NIH HHS [P01 CA050661, P01 CA50661] NR 53 TC 63 Z9 63 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD AUG PY 2007 VL 5 IS 8 BP 1810 EP 1819 AR e202 DI 10.1371/journal.pbio.0050202 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 205OT UT WOS:000249124800017 PM 17608567 ER PT J AU Lee, JM Ivanova, EV Seong, IS Cashorali, T Kohane, I Gusella, JF MacDonald, ME AF Lee, Jong-Min Ivanova, Elena V. Seong, Ihn Sik Cashorali, Tanya Kohane, Isaac Gusella, James F. MacDonald, Marcy E. TI Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism SO PLOS GENETICS LA English DT Article ID STRIATAL CELLS; MUTANT HUNTINGTIN; IN-VITRO; TRANSCRIPTIONAL REPRESSION; 3-NITROPROPIONIC ACID; H-1-NMR SPECTROSCOPY; DISEASE; REPEAT; DEFECTS; PROTEIN AB The Huntington's disease (HD) CAG repeat, encoding a polymorphic glutamine tract in huntingtin, is inversely correlated with cellular energy level, with alleles over; 37 repeats leading to the loss of striatal neurons. This early HD neuronal specificity can be modeled by respiratory chain inhibitor 3-nitropropionic acid ( 3-NP) and, like 3-NP, mutant huntingtin has been proposed to directly influence the mitochondrion, via interaction or decreased PGC-1 alpha expression. We have tested this hypothesis by comparing the gene expression changes due to mutant huntingtin accurately expressed in STHdh (Q111/ Q111) cells with the changes produced by 3-NP treatment of wild-type striatal cells. In general, the HD mutation did not mimic 3-NP, although both produced a state of energy collapse that was mildly alleviated by the PGC-1 alpha-coregulated nuclear respiratory factor 1 ( Nrf-1). Moreover, unlike 3-NP, the HD CAG repeat did not significantly alter mitochondrial pathways in STHdh Q111/ Q111 cells, despite decreased Ppargc1a expression. Instead, the HD mutation enriched for processes linked to huntingtin normal function and Nf-kappa B signaling. Thus, rather than a direct impact on the mitochondrion, the polyglutamine tract may modulate some aspect of huntingtin's activity in extra-mitochondrial energy metabolism. Elucidation of this HD CAG-dependent pathway would spur efforts to achieve energy-based therapeutics in HD. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. Huntingtons Dis Soc Amer Coalit Cure Mitochondria, New York, NY USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM macdonam@helix.mgh.harvard.edu RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NINDS NIH HHS [NS16367, NS32765, P50 NS016367, R01 NS032765]; NLM NIH HHS [U54 LM008748, LM008748] NR 56 TC 48 Z9 48 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2007 VL 3 IS 8 BP 1397 EP 1406 AR e135 DI 10.1371/journal.pgen.0030135 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 214VZ UT WOS:000249767600008 PM 17708681 ER PT J AU Van Stone, WW AF Van Stone, William W. TI Treating health anxiety and fear of death: A practitioner's guide SO PSYCHIATRIC SERVICES LA English DT Book Review C1 [Van Stone, William W.] US Dept Vet Affairs, Vet Affairs Cent Off, Off Mental Hlth Serv, Washington, DC USA. RP Van Stone, WW (reprint author), US Dept Vet Affairs, Vet Affairs Cent Off, Off Mental Hlth Serv, Washington, DC USA. NR 1 TC 0 Z9 0 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG PY 2007 VL 58 IS 8 BP 1129 EP 1130 DI 10.1176/appi.ps.58.8.1129 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 265LN UT WOS:000253360500022 ER PT J AU Young, EA Kornstein, SG Harvey, AT Wisniewski, SR Barkin, J Fava, M Trivedi, MH Rush, AJ AF Young, Elizabeth A. Kornstein, Susan G. Harvey, Anne T. Wisniewski, Stephen R. Barkin, Jennifer Fava, Maurizio Trivedi, Madhukar H. Rush, A. John TI Influences of hormone-based contraception on depressive symptoms in premenopausal women with major depression SO PSYCHONEUROENDOCRINOLOGY LA English DT Article ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; PLACEBO-CONTROLLED TRIAL; ILLNESS RATING-SCALE; REPORT QIDS-SR; ORAL-CONTRACEPTIVES; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; POSTNATAL DEPRESSION; MOOD DISORDERS AB Objective: Hormone-based contraceptives affect mood in healthy women or in women with premenstrual dysphoric disorder (PMDD). No study has yet examined their association with mood in women with major depressive disorder (MDD). The purpose of this study was to determine whether estrogen-progestin combination or progestin-only contraceptives are associated with depression severity, function and quality of life, or general medical or psychiatric comorbidity in women with MDD. Methods: This analysis focused on a large population of female outpatients less than 40 years of age with non-psychotic MDD who were treated in 18 primary and 23 psychiatric care settings across the US, using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Baseline demographic and clinical information was gathered and compared between three groups based on hormonal use: combination (estrogen-progestin)(N = 232), progestin-only (N = 58), and no hormone treatment (N = 948). Results: Caucasians were significantly more likely to use combined hormone contraception. Women on progestin-only had significantly more general medical comorbidities; greater hypersomnia, weight gain and gastrointestinal symptoms; and worse physical functioning than women in either of the other groups. Those on combined hormone contraception were significantly less depressed than those with no hormone treatment by the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated. The combined hormone group also demonstrated better physical functioning and less obsessive-compulsive disorder (COCD) comorbidity than either of the other groups. Conclusions: Synthetic estrogen and progestins may influence depressive and physical symptoms in depressed women. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Michigan, Dept Psychiat, MBNI, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Sch Med, Dept Obstet & Gynecol, Richmond, VA 23298 USA. Via Christi Res Inc, Wichita, KS 67214 USA. Univ Pittsburgh, GSPH, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. RP Young, EA (reprint author), Univ Michigan, Dept Psychiat, MBNI, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM eayoung@umich.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH90003, N01MH90003, K05 MH001931-05] NR 41 TC 32 Z9 35 U1 4 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD AUG PY 2007 VL 32 IS 7 BP 843 EP 853 DI 10.1016/j.psyneuen.2007.05.013 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 211FR UT WOS:000249510200009 PM 17629629 ER PT J AU Andrei, AM Fraguas, R Telles, RMS Alves, TCTF Strunz, CMC Nussbacher, A Rays, J Iosifescu, DV Wajngarten, M AF Andrei, Anna Maria Fraguas, Renerio, Jr. Telles, Renata M. S. Alves, Tania C. T. F. Strunz, Celia M. C. Nussbacher, Amit Rays, Jairo Iosifescu, Dan V. Wajngarten, Mauricio TI Major depressive disorder and inflammatory markers in elderly patients with heart failure SO PSYCHOSOMATICS LA English DT Article ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; CORONARY-ARTERY-DISEASE; ACUTE-PHASE PROTEINS; CARDIAC MYOCYTES; NITRIC-OXIDE; CARDIOVASCULAR EVENTS; CLINICAL DEPRESSION; CIRCULATING LEVELS; IMMUNE ACTIVATION AB The authors evaluated levels of inflammatory markers in 34 chronic heart failure (CHF) outpatients age 65 years and over, with (N = 18) and without (N = 16) major depressive disorder (MDD), and healthy-control subjects (N = 13). Patients with CHF had left-ventricular ejection fractions < 0.40 and were in the New York Heart Association functional class II or III. The authors used the SCID DSM-IV to diagnosis MDD. High-sensitivity C-reactive protein levels were significantly higher in patients with CHF and MDD as compared with healthy-control subjects. No differences regarding tumor necrosis factor(alpha) or interleukin(6) were found among the three groups. C1 Univ Sao Paulo, Sch Med, Inst Heart, BR-05508 Sao Paulo, Brazil. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Inst Psychiat, BR-05508 Sao Paulo, Brazil. RP Fraguas, R (reprint author), Univ Sao Paulo, Sch Med, Inst Heart, BR-05508 Sao Paulo, Brazil. EM rfraguas@partners.org RI Alves, Tania/B-6571-2008; Strunz, Celia /G-5562-2011; Wajngarten, Mauricio/G-3702-2012; Alves, Tania/H-3416-2013; Andrei, Anna Maria/P-5207-2015 OI Alves, Tania/0000-0003-3402-9656; Strunz, Celia /0000-0002-9766-1184; Alves, Tania/0000-0003-3402-9656; NR 63 TC 17 Z9 18 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD AUG PY 2007 VL 48 IS 4 BP 319 EP 324 DI 10.1176/appi.psy.48.4.319 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 184DC UT WOS:000247620300007 PM 17600168 ER PT J AU Fedele, S Fricchione, G Porter, SR Mignogna, MD AF Fedele, S. Fricchione, G. Porter, S. R. Mignogna, M. D. TI Burning mouth syndrome (stomatodynia) SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Editorial Material ID PAIN; GLOSSODYNIA; PERSPECTIVE; MANAGEMENT; CLONAZEPAM C1 UCL, Eastman Dent Inst, Div Maxillofacial Diagnost Med & Surg Sci, Oral Med Unit, London WC1X 8LD, England. Univ Naples Federico 2, Div Oral Med, Dept Odontostomatol & Maxillofacial Sci, Naples, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fedele, S (reprint author), UCL, Eastman Dent Inst, Div Maxillofacial Diagnost Med & Surg Sci, Oral Med Unit, 256 Grays Inn Rd, London WC1X 8LD, England. EM s.fedele@eastman.ucl.ac.uk RI Porter, Stephen/B-3519-2009 NR 32 TC 20 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD AUG PY 2007 VL 100 IS 8 BP 527 EP 530 DI 10.1093/qjmed/hcm049 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 201CQ UT WOS:000248809500007 PM 17601771 ER PT J AU Thrall, JH AF Thrall, James H. TI Teleradiology - Part II. Limitations, risks, and opportunities SO RADIOLOGY LA English DT Editorial Material ID RADIOLOGY 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 6 TC 31 Z9 31 U1 0 U2 2 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 AUG PY 2007 VL 244 IS 2 BP 325 EP 328 DI 10.1148/radiol.2442070676 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 201HF UT WOS:000248821400002 PM 17641358 ER PT J AU Lehman, CD Isaacs, C Schnall, MD Pisano, ED Ascher, SM Weatherall, PT Bluemke, DA Bowen, DJ Marcom, PK Armstrong, DK Domchek, SM Tomlinson, G Skates, SJ Gatsonis, C AF Lehman, Constance D. Isaacs, Claudine Schnall, Mitchell D. Pisano, Etta D. Ascher, Susan M. Weatherall, Paul T. Bluemke, David A. Bowen, Deborah J. Marcom, P. Kelly Armstrong, Deborah K. Domchek, Susan M. Tomlinson, Gail Skates, Steven J. Gatsonis, Constantine TI Cancer yield of mammography, MR, and US in high-risk women: Prospective multi-institution breast cancer screening study SO RADIOLOGY LA English DT Article ID BRCA2 MUTATION CARRIERS; BILATERAL PROPHYLACTIC MASTECTOMY; HIGH FAMILIAL RISK; DENSE BREASTS; OOPHORECTOMY; GENE; SURVEILLANCE; POPULATION; SONOGRAPHY; EFFICACY AB Purpose: To prospectively determine cancer yield, callback and biopsy rates, and positive predictive value (PPV) of mammography, magnetic resonance ( MR) imaging, and ultrasonography (US) in women at high risk for breast cancer. Materials and Methods: The study was approved by the institutional review board and was HIPAA compliant, and informed consent was obtained. We conducted a prospective pilot study of screening mammography, MR, and US in asymptomatic women 25 years of age or older who were genetically at high risk, defined as BRCA1/ BRCA2 carriers or with at least a 20% probability of carrying a BRCA1/ BRCA2 mutation. All imaging modalities were performed within 90 days of each other. Data were analyzed by using exact confidence intervals (CIs) and the McNemar test. Results: A total of 195 women were enrolled in this study over a 6- month period, and 171 completed all study examinations (mammography, US, and MR). Average age of the 171 participants was 46 years +/- 10.2 (standard deviation). Sixteen biopsies were performed and six cancers were detected, for an overall 3.5% cancer yield. MR enabled detection of all six cancers; mammography, two; and US, one. The diagnostic yields for each test were 3.5% for MR, 0.6% for US, and 1.2% for mammography. MR, US, and mammography findings prompted biopsy in 8.2%, 2.3%, and 2.3% of patients, respectively. None of the pairwise comparisons were statistically significant. The PPV of biopsies performed as a result of MR was 43%. Conclusion: Screening MR imaging had a higher biopsy rate but helped detect more cancers than either mammography or US. US had the highest false-negative rate compared with mammography and MR, enabling detection of only one in six cancers in high- risk women. C1 Univ Washington, Med Ctr, Dept Radiol, Seattle Canc Care Alliance, Seattle, WA 98109 USA. Georgetown Univ, Dept Med, Lombardi Comprehens Canc Ctr, Washington, DC USA. Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Ctr Breast Care, Dallas, TX 75235 USA. Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Med Oncol, Baltimore, MD USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Dept Med Oncol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. RP Lehman, CD (reprint author), Univ Washington, Med Ctr, Dept Radiol, Seattle Canc Care Alliance, 825 Eastlake Ave E, Seattle, WA 98109 USA. EM lehman@seattlecca.org OI Bluemke, David/0000-0002-8323-8086 FU NCI NIH HHS [5 U01 CA74696, U01 CA74680, U24 CA78146-01] NR 32 TC 171 Z9 180 U1 1 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 AUG PY 2007 VL 244 IS 2 BP 381 EP 388 DI 10.1148/radiol.2442060461 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 201HF UT WOS:000248821400007 PM 17641362 ER PT J AU Camargo, ECS Furie, KL Singhal, AB Roccatagliata, L Cunnane, ME Halpern, EF Harris, GJ Smith, WS Gonzalez, RG Koroshetz, WJ Lev, MH AF Camargo, Erica C. S. Furie, Karen L. Singhal, Aneesh B. Roccatagliata, Luca Cunnane, Mary E. Halpern, Elkan F. Harris, Gordon J. Smith, Wade S. Gonzalez, Ramon G. Koroshetz, Walter J. Lev, Michael H. TI Acute brain infarct: Detection and delineation with CT angiographic source images versus nonenhanced CT scans SO RADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; DYNAMIC PERFUSION CT; COMPUTED-TOMOGRAPHY; HYPERACUTE STROKE; UNENHANCED CT; THROMBOLYSIS; PREDICTION; VOLUME; EXTENT; SCORE AB Purpose: To retrospectively compare sensitivity and specificity of admission nonenhanced computed tomographic (CT) scans with those of CT angiographic source images in detection of early ischemic changes in middle cerebral artery (MCA) stroke and to retrospectively compare admission nonenhanced CT scans with CT angiographic source images in delineation of final infarct extent, with follow-up images as reference. Materials and Methods: Informed consent and institutional review board approval were received for this HIPAA-compliant study. Nonenhanced scans and angiographic source images obtained within 12 hours of symptom onset in 51 patients suspected of having MCA stroke were reviewed. Two blinded neuroimagers rated presence and extent of hypoattenuation on nonenhanced scans and angiographic source images with Alberta Stroke Programme Early CT Score (ASPECTS). Level of certainty for hypoattenuation detection was assigned a grade with a five- point scale. With receiver operating characteristic (ROC) curve analysis, nonenhanced scans and angiographic source images were compared for stroke detection. For stroke delineation, linear regression coefficients determined correlations of ASPECTS for nonenhanced scans and angiographic source images with ASPECTS for follow-up images. Multiple linear regressions were used to compare these correlations. Results: Follow-up nonenhanced CT scans, diffusion-weighted magnetic resonance (MR) images, or fluid-attenuated inversionrecovery MR images were obtained (mean time to follow-up, 5.4 days); 33 patients had infarction. With level of certainty cutoff score of 4 or greater (probable, definite) for ischemic hypoattenuation, sensitivity for detection of acute stroke was 48% (nonenhanced scans) and 70% ( angiographic source images) (P =.04, ROC analysis); specificity was 100% for both. Linear regression revealed R-2 = 0.42 (P <.001) for correlation between delineation of stroke on nonenhanced scans and on follow-up images evaluated with ASPECTS and 0.73 (P <. 001) for correlation between delineation on angiographic source images and follow- up images evaluated with ASPECTS (P <.001, nonenhanced scans vs angiographic source images). Conclusion: CT angiographic source images, compared with nonenhanced CT scans, are more sensitive in detection of early irreversible ischemia and more accurate for prediction of final infarct volume. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Lev, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,GRB-239, Boston, MA 02114 USA. EM mlev@partners.org FU AHRQ HHS [R01 HS11392] NR 20 TC 73 Z9 74 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2007 VL 244 IS 2 BP 541 EP 548 DI 10.1148/radiol.2442061028 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 201HF UT WOS:000248821400025 PM 17581888 ER PT J AU Singh, AK Sahani, DV Kagay, CR Kalva, SP Joshi, MC Elias, N Kawai, T AF Singh, Anand Kumar Sahani, Dushyant V. Kagay, Christopher R. Kalva, Sanjeeva P. Joshi, Mukta C. Elias, Nahel Kawai, Tatsuo TI Semiautomated MIP images created directly on 16-section multidetector CT console for evaluation of living renal donors SO RADIOLOGY LA English DT Article ID HELICAL CT; ANGIOGRAPHY; NEPHRECTOMY; EXPERIENCE AB Institutional Review Board approval was obtained and informed consent was waived for this HIPAA-compliant study. The aim of this study was to retrospectively compare the accuracy of semiautomated maximum intensity projection (MIP) images created at a 16-section multidetector CT console with three-dimensional (3D)-workstation-generated images for the definition of renal donor anatomy, with intraoperative findings as a reference standard. In examining 40 renal donors ( 21 men and 19 women; age range, 24-56 years; mean age, 40.4 years), the sensitivity and accuracy for mapping donor anatomy by two readers were greater than 95%, interobserver agreement was excellent ( k = 0.89 - 1.00). The 95% confidence interval for sensitivity was also calculated. Simple MIPs compared well with 3D-workstation images. MIPs from a predesigned protocol on the scanner console were generated more quickly than similar images from 3D workstations; postprocessing demands (eg, for renal donors) can be quickly fulfilled at the scanner console itself. The average time to generate simple MIPs at the console was 3.4 minutes ( range, 1.7-4.4 minutes), and 22.3 minutes ( range, 15 - 30 minutes) to create images at the 3D workstation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. GE Healthcare, Dept FCT Engn, Belmont, MA USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 18 TC 8 Z9 11 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2007 VL 244 IS 2 BP 583 EP 590 DI 10.1148/radiol.2442060909 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 201HF UT WOS:000248821400030 PM 17641376 ER PT J AU Munroe, CA Sirdofsky, MD Kuru, T Anderson, ED AF Munroe, Craig A. Sirdofsky, Michael D. Kuru, Tunay Anderson, Eric D. TI End-of-life decision making in 42 patients with amyotrophic lateral sclerosis SO RESPIRATORY CARE LA English DT Article DE amyotrophic lateral sclerosis; end-of-life; do-not resuscitate; do-not-intubate; DNR; DNI; pulmonary functions testing; bulbar dysfunction ID CARE; ALS; ATTITUDES AB OBJECTIVE: To determine when end-of-life issues were discussed with patients afflicted with amyotrophic lateral sclerosis (ALS). METHODS: This was a retrospective analysis of ALS patients referred to the neuromuscular clinic at Georgetown University Hospital. Patients were seen by a pulmonologist and a neurologist at the initial diagnosis or referral, and every 2-3 months thereafter. End-of-life discussions were addressed at each visit. Other variables recorded included the amount of time afflicted with ALS, serial pulmonary function test results, and the subjective level of bulbar dysfunction. RESULTS: We saw 43 patients (age range 39-94 y) between June 1999 and September 2004. One patient was on a ventilator at the initial visit, and was therefore excluded from the study. Discussion about the patients' end-of-life care preferences were initiated at the first pulmonary visit with 40 patients. With 2 patients, end-of-life decisions were discussed at the second office visit. Twenty-five patients chose do-not-resuscitate and do-not-intubate (DNR/DNI) orders after the initial end-of-life discussion with the pulmonologist. Five other patients chose DNR/DNI orders during subsequent clinic visits. Four patients were still undecided at their last clinic visit. Six patients were lost to follow-up before a decision was made. Two patients requested full ventilatory support. Both the forced vital capacity and the level of bulbar dysfunction were not statistically different between the patients who chose DNR/DNI and the patients who were either undecided or requested full ventilatory support. CONCLUSIONS: Decisions about end-of-life care are often delayed in patients with ALS. These patients' final decisions seem to be independent of their level of respiratory insufficiency or bulbar function, and most related to the physician addressing endof-life care decisions in a timely manner. C1 Georgetown Univ, Dept Pulm Crit Care & Sleep Med, Washington, DC USA. Georgetown Univ, Dept Neurol, Washington, DC USA. RP Munroe, CA (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM camunroe@partners.org NR 8 TC 18 Z9 18 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 RESP CARE JI Respir. Care PD AUG PY 2007 VL 52 IS 8 BP 996 EP 999 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 198EB UT WOS:000248608700005 PM 17650354 ER PT J AU Ramnath, VR Clark, S Camargo, CA AF Ramnath, Venktesh R. Clark, Sunday Camargo, Carlos A., Jr. TI Multicenter study of clinical features of sudden-onset versus slower-onset asthma exacerbations requiring hospitalization SO RESPIRATORY CARE LA English DT Article DE sudden-onset asthma; emergency department; intensive care unit; intubation ID VOCAL-CORD DYSFUNCTION; NEAR-FATAL ASTHMA; EMERGENCY-DEPARTMENT; BETA(2)-ADRENERGIC RECEPTOR; DISTINCT ENTITY; ADULTS; SALMETEROL; CARE; ADMISSION; ALBUTEROL AB Background: Asthma exacerbations differ in their speed of symptom onset. Objective: To characterize and compare demographic factors, clinical risk factors, and clinical outcomes among hospitalized patients who presented with sudden-onset (<= 3 h) versus slower-onset asthma exacerbations, across a wide age range. Methods: We reviewed the medical records of a random sample of 1,294 patients, ages 2-54 years, admitted in 30 United States hospitals, for acute asthma from January 1999 to May 2000. Results: Data on duration of symptoms were available for 1,260 (97%) of the patients. Seventy-two patients (6%) had sudden-onset exacerbations. Sudden-onset patients were older than slower-onset patients (30 y vs 19 y, p = 0.03) but did not differ by other sociodemographic characteristics. Markers of chronic asthma severity were similar between the groups. The sudden-onset patients were more likely to present to the emergency department between midnight and 8:00 AM, to require intubation, and to be admitted to the intensive care unit (all p < 0.01). The higher risk of intensive care unit admission remained significant even after adjustment for 6 potential confounders (odds ratio 2.5, 95% confidence interval 1.3-4.9). However, hospital stay was shorter in the sudden-onset patients (2.0 d vs 2.7 d, p = 0.01). There was no difference in peak expiratory flow at hospital discharge. Conclusions: The sudden-onset patients were older and they more commonly presented to the emergency department between midnight and 8:00 AM with severe exacerbations that required intubation and intensive care unit admission. However, the sudden-onset group was discharged from the hospital earlier. C1 Massachusetts Gen Hosp, Dept Emergency Med, Emergency Med Network Coordinating Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Emergency Med Network Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 44 TC 10 Z9 10 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD AUG PY 2007 VL 52 IS 8 BP 1013 EP 1020 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 198EB UT WOS:000248608700008 PM 17650357 ER PT J AU Shaner, A Miller, G Mintz, J AF Shaner, Andrew Miller, Geoffrey Mintz, Jim TI Evidence of a latitudinal gradient in the age at onset of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; latitudinal gradient; age at onset; evolution; sexual selection; migration; fitness indicator ID LEK PARADOX; METAANALYSIS; DISORDERS; EVOLUTION; PSYCHOSIS; MENARCHE; DISEASE; PUBERTY; FITNESS; BIRTH AB Variation in the age at onset of a multifactorial disease often reflects variation in cause. Here we show a linear latitudinal gradient in the mean age at onset of schizophrenia in 13 northern hemisphere cities, ranging from 25 years old in Cali, Columbia (at 4 degrees north) to 35 years old in Moscow, Russia (at 56 degrees north). To our knowledge, this striking association has not been previously reported. We consider several explanations, including the effects of pathogen stress, natural selection, sexual selection, migration, life-history profiles, or some combination of these factors, and we propose a test of competing causal hypotheses. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. RP Shaner, A (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Andrew.Shaner@med.va.gov; gfmiller@unm.edu; JMintz@ucla.edu RI Miller, Geoffrey/C-4145-2008 NR 38 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2007 VL 94 IS 1-3 BP 58 EP 63 DI 10.1016/j.schres.2007.04.001 PG 6 WC Psychiatry SC Psychiatry GA 198OX UT WOS:000248638500008 PM 17509836 ER PT J AU Fan, XD Henderson, DC Chiang, E Briggs, LBN Freudenreich, O Evins, AE Cather, C Goff, DC AF Fan, Xiaoduo Henderson, David C. Chiang, Elaine Briggs, Leah B. Narney Freudenreich, Oliver Evins, A. Eden Cather, Corinne Goff, Donald C. TI Sexual functioning, psychopathology and quality of life in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; sexual functioning; quality of life ID ANTIPSYCHOTIC MEDICATION; ERECTILE DYSFUNCTION; QUESTIONNAIRE CSFQ; CONSTRUCT-VALIDITY; RATING-SCALE; RELIABILITY; CLOZAPINE AB Objective: The present study was to characterize relationships among sexual functioning, schizophrenia symptoms and quality of life measures. In addition, sexual functioning was compared among patients treated with different antipsychotic agents. Methods: Outpatient subjects were assessed using the Positive and Negative Symptom Scale (PANSS), the Changes in Sexual Functioning Questionnaire (CSFQ) and the Hamilton Rating Scale for Depression (HAMD). Quality of life was assessed using two different instruments: observer-rated Heinrich's Quality of Life Scale (QLS) and self-rated The Behavior and Symptom Identification Scale (BASIS). Results: One hundred twenty-four patients with schizophrenia or schizoaffective disorder were enrolled in the study. Eight-six patients (69%) completed at least part of the CSFQ assessment, which generated at least one valid subscale score. High rates of sexual impairment were found in both male and female patients (65%-94% across different subscales). For males, higher scores on the PANSS-positive subscale were associated with a lower frequency of sexual activity (p=0.04). For females, higher scores on the PANSS-positive subscale and PANSS-general psychopathology subscale were significantly associated with more difficulty in both sexual arousal and orgasm (p's < 0.05). For both males and females, there were no significant relationships between any CSFQ subscale measures and the quality of life measures (p's > 0.05). No significant differences were found among three antipsychotic treatment groups (clozapine, olanzapine or typical agents) on any CSFQ subscale measures or quality of life measures after controlling for PANSS total scores (p's > 0.05). Conclusions: Effective treatment strategies still need to be developed to address sexual dysfunction and quality of life in patients with schizophrenia. (C) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Worcester Acad, Worcester, MA USA. RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xfan@partners.org FU NIMH NIH HHS [MH02025] NR 34 TC 23 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2007 VL 94 IS 1-3 BP 119 EP 127 DI 10.1016/j.schres.2007.04.033 PG 9 WC Psychiatry SC Psychiatry GA 198OX UT WOS:000248638500016 PM 17590315 ER PT J AU Wisco, JJ Kuperberg, G Manoach, D Quinn, BT Busa, E Fischl, B Heckers, S Sorensen, AG AF Wisco, Jonathan J. Kuperberg, Gina Manoach, Dara Quinn, Brian T. Busa, Evelina Fischl, Bruce Heckers, Stephan Sorensen, A. Gregory TI Abnormal cortical folding patterns within Broca's area in schizophrenia: Evidence from structural MRI SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; MRI; cortical folding; Broca's area; language ID DORSOLATERAL PREFRONTAL CORTEX; AUDITORY VERBAL HALLUCINATIONS; WORKING-MEMORY; THOUGHT-DISORDER; 1ST-EPISODE SCHIZOPHRENIA; CEREBRAL-CORTEX; FUNCTIONAL MRI; TEMPORAL-LOBE; COORDINATE SYSTEM; NEGATIVE-SYMPTOMS AB We compared cortical folding patterns between patients with schizophrenia and demographically-matched healthy controls in prefrontal and temporal regions of interest. Using the Freesurfer (http://surfer.nmr.mgh.harvard.edu) cortical surface-based reconstruction methodology, we indirectly ascertained cortical displacement and convolution, together, by measuring the degree of metric distortion required to optimally register cortical folding patterns to an average template. An area within the pars triangularis of the left inferior frontal gyrus (Broca's area) showed significantly reduced metric distortion in the patient group relative to the control group (p=0.0352). We discuss these findings in relation to the neurodevelopmental hypothesis and language dysfunction in schizophrenia. (c) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. MIT, HST, MIT, Cambridge, MA 02139 USA. MIT, CSAIL, Inst Technol, Cambridge, MA 02139 USA. RP Wisco, JJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 10833 Le Conte Ave,Room 52-060, Los Angeles, CA 90095 USA. EM jjwisco@mednet.ucla.edu; kuperber@nmr.mgh.harvard.edu; dara@nmr.mgh.harvard.edu; btquinn@nmr.mgh.harvard.edu; evelina@nmr.mgh.harvard.edu; fischl@nmr.mgh.harvard.edu; stephan.heckers@Vanderbilt.Edu; sorensen@nmr.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NCI NIH HHS [5T32 CA09502, T32 CA009502, T32 CA009502-19]; NCRR NIH HHS [P41 RR014075, P41 RR014075-08, P41-RR14075, R01 RR016594, R01 RR016594-01A1, R01 RR16594-01A1, U24 RR021382, U24 RR021382-03]; NIBIB NIH HHS [R01 EB001550, U54 EB005149]; NIMH NIH HHS [R01 MH067720, R01 MH067720-03, R01 MH071635]; NINDS NIH HHS [R01 NS052585, R01 NS052585-01, R01 NS052585-01A1] NR 93 TC 46 Z9 47 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2007 VL 94 IS 1-3 BP 317 EP 327 DI 10.1016/j.schres.2007.03.031 PG 11 WC Psychiatry SC Psychiatry GA 198OX UT WOS:000248638500039 PM 17490861 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, Kai W. TI The structure and function of antigen receptors SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kai-wucherpfennig@dfci.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD AUG PY 2007 VL 19 IS 4 BP 215 EP 215 DI 10.1016/j.simm.2007.04.004 PG 1 WC Immunology SC Immunology GA 199VD UT WOS:000248722400001 ER PT J AU Wucherpfennig, KW Allen, PM Celada, F Cohen, IR De Boer, R Garcia, KC Goldstein, B Greenspan, R Hafler, D Hodgkin, P Huseby, ES Krakauer, DC Nemazee, D Perelson, AS Pinilla, C Strong, RK Sercarz, EE AF Wucherpfennig, Kai W. Allen, Paul M. Celada, Franco Cohen, Irun R. De Boer, Rob Garcia, K. Christopher Goldstein, Byron Greenspan, Ralph Hafler, David Hodgkin, Philip Huseby, Erik S. Krakauer, David C. Nemazee, David Perelson, Alan S. Pinilla, Clemencia Strong, Roland K. Sercarz, Eli E. TI Polyspecificity of T cell and B cell receptor recognition SO SEMINARS IN IMMUNOLOGY LA English DT Review DE T cell receptor; peptide; MHC; polyspecificity; recognition ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; CROSS-REACTIVITY; PEPTIDE-MHC; STRUCTURAL REQUIREMENTS; DEGENERATE RECOGNITION; ANTIGENIC PEPTIDE; SELF; SPECIFICITY; AUTOIMMUNITY AB A recent workshop discussed the recognition of multiple distinct ligands by individual T cell and B cell receptors and the implications of this discovery for lymphocyte biology. The workshop recommends general use of the term polyspecificity because it emphasizes two fundamental aspects, the inherent specificity of receptor recognition and the ability to recognize multiple ligands. Many different examples of polyspecificity and the structural mechanisms were discussed, and the group concluded that polyspecificity is a general, inherent feature of TCR and antibody recognition. This review summarizes the relevance of polyspecificity for lymphocyte development, activation and disease processes. (c) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Univ Utrecht, Dept Theoret Biol, Utrecht, Netherlands. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Biol Struct, Stanford, CA 94305 USA. Los Alamos Natl Lab, Theoret & Phys Biol Grp, Los Alamos, NM 87545 USA. Inst Neurosci, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. Natl Jewish Med & Res Ctr, Howard Hughes Med Inst, Denver, CO 80206 USA. Natl Jewish Med & Res Ctr, Dept Integrat Immunol, Denver, CO 80206 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Los Alamos Natl Lab, Dept Theoret Biol & Biophys, Los Alamos, NM 87545 USA. Torrey Pines Inst Mol Studies, Dept Immunochem, San Diego, CA 92121 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Torrey Pines Inst Mol Studies, Div Immune Regulat, San Diego, CA 92121 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu RI Cohen, Irun/B-3542-2009; De Boer, Rob/B-6050-2011 OI De Boer, Rob/0000-0002-2130-691X FU NIAID NIH HHS [R01 AI064177, P01 AI045757, P01 AI045757-09, R01 AI033608, R01 AI064177-03, R13 AI068354, R13 AI068354-01]; NIGMS NIH HHS [R01 GM044809] NR 46 TC 91 Z9 93 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD AUG PY 2007 VL 19 IS 4 BP 216 EP 224 DI 10.1016/j.simm.2007.02.012 PG 9 WC Immunology SC Immunology GA 199VD UT WOS:000248722400002 PM 17398114 ER PT J AU Grabowski, EF Buonanno, FS Krishnamoorthy, K AF Grabowski, Eric F. Buonanno, Ferdinando S. Krishnamoorthy, Kalpathy TI Prothrombotic risk factors in the evaluation and management of perinatal stroke SO SEMINARS IN PERINATOLOGY LA English DT Review DE perinatal stroke; prothrombotic risk factors; thrombophilia; maternal preeclampsia; placental pathology; diagnostic imaging; anticoagulation ID FACTOR-V-LEIDEN; PROTEIN-S DEFICIENCY; ISCHEMIC-STROKE; CHILDHOOD STROKE; METHYLENETETRAHYDROFOLATE REDUCTASE; SEVERE PREECLAMPSIA; PEDIATRIC STROKE; CHILDREN; THROMBOSIS; INFANTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Hematol Oncol, Yawkey 8B,55 Fruit St, Boston, MA 02114 USA. EM Grabowski.Eric@MGH.Harvard.edu NR 45 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD AUG PY 2007 VL 31 IS 4 BP 243 EP 249 DI 10.1053/j.semperi.2007.06.001 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 212SH UT WOS:000249616600010 PM 17825681 ER PT J AU Singh, AK Gonzalez-Torrez, P Kaewlai, R Tabatabaei, S Harisinghani, MG AF Singh, Ajay K. Gonzalez-Torrez, Pedro Kaewlai, Rathachai Tabatabaei, Shahin Harisinghani, Mukesh G. TI Imaging of penile neoplasm SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CANCER; HISTOPATHOLOGY; EXPERIENCE C1 Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), 10 Museum Way 524, Boston, MA 02141 USA. EM mghpartners@yahoo.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 26 TC 10 Z9 11 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 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD AUG PY 2007 VL 28 IS 4 BP 287 EP 296 DI 10.1053/j.sult.2007.05.005 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 201EP UT WOS:000248814600006 PM 17874652 ER PT J AU Fan, J Li, YH Vodovotz, Y Billiar, TR Wilson, MA AF Fan, Jie Li, Yuehua Vodovotz, Yoram Billiar, Timothy R. Wilson, Mark A. TI Neutrophil NAD(P)H oxidase is required for hemorrhagic shock-enhanced TLR2 up-regulation in alveolar macrophages in response to LPS SO SHOCK LA English DT Article DE acute lung injury; innate immunity; IRAK4 ID FACTOR-KAPPA-B; NADPH OXIDASE; ENDOTHELIAL-CELLS; ORGAN INJURY; EXPRESSION; LUNG; LIPOPOLYSACCHARIDE; ACTIVATION; INFLAMMATION; THIOREDOXIN AB Alveolar macrophages (AMs) play an important role in the development of posttrauma lung inflammation through initiating polymorphonuclear neutrophil (PMN) migration by direct interactions with PMN, which is in turn mediated by the expression of chemokines and cytokines. We have recently reported that hemorrhagic shock-activated PMN sensitize AM to bacteria LPS for the up-regulation of Toll-like receptor (TLR)2; in turn, this TLR2 up-regulation results in the amplification of expression of cytokines and chemokines in the AM in response to the bacterial products LPS and peptidoglycan, associated with enhanced PMN sequestration in the lung. We sought to address the mechanism underlying the augmentation of TLR2 in AM by shock-activated PMN. We found that hemorrhagic shock/resuscitation (shock) followed by a low dose of i.t. LPS markedly increased TLR2 mRNA expression in AM in wild-type (WT) mice. In contrast, in mice lacking the gp91(phox) subunit of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase (gp91(Phox-/-)) or in neutropenic WT mice, the increase in TLR2 mRNA was attenuated. Coculture of AM with PMN derived from WT-shocked mice caused a significantly higher level of TLR2 expression in the AM in response to LPS. However, this increase in TLR2 expression was less evident when the AMs were cocultured with PMN derived from gp91(Phox-/-) mice subjected to shock. The antioxidant polyethylene glycol catalase markedly decreased MyD88-dependent activation of IL-1 receptor associated kinase 4 and TLR2 expression in the AM in response to LPS. Thus, PMN nicotinamide adenine dinucleotide phosphate (reduced form) oxidase sensitizes hemorrhagic shock-primed AM to LPS, at least in part via enhancing IL-1 receptor associated kinase 4 activity. C1 VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15260 USA. RP Fan, J (reprint author), VA Pittsburgh Healthcare Syst, Dept Surg, CHERP Bldg 28 151C-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM jif7@pitt.edu FU NHLBI NIH HHS [R01 HL 079669]; NIGMS NIH HHS [P50 GM 53789] NR 29 TC 18 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD AUG PY 2007 VL 28 IS 2 BP 213 EP 218 DI 10.1097/shk.0b013e318033ec9d PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 193SV UT WOS:000248295800014 PM 17515854 ER PT J AU Sundaram, M Rosenthal, DI AF Sundaram, M. Rosenthal, D. I. TI Change of European editor SO SKELETAL RADIOLOGY LA English DT Biographical-Item C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sundaram, M (reprint author), Cleveland Clin Fdn, Diagnost Radiol A21,9500 Euclid Ave, Cleveland, OH 44195 USA. EM sundarm@ccf.org; dirosenthal@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2007 VL 36 IS 8 BP 709 EP 709 DI 10.1007/s00256-007-0345-z PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 181YV UT WOS:000247473200001 PM 17569042 ER PT J AU Kattapuram, TM Ozhathil, DK Hornicek, FJ Gebhardt, MC Mankin, HJ Rosenberg, AE Kattapuram, SV AF Kattapuram, Taj M. Ozhathil, Deepak K. Hornicek, Francis J. Gebhardt, Mark C. Mankin, Henry J. Rosenberg, Andrew E. Kattapuram, Susan V. TI Imaging of pseudoneoplastic masses associated with allografts SO SKELETAL RADIOLOGY LA English DT Article DE allografts; pseudoneoplasms; musculoskeletal tumors; imaging ID BONE ALLOGRAFTS; MUSCULOSKELETAL TUMORS; FOLLOW-UP; OSTEOSARCOMA; MANAGEMENT; FRACTURES AB Objective The objective of this study is to describe the imaging features of non-neoplastic masses suspected of being tumor recurrences adjacent to allografts. The allografts were utilized for the treatment of various musculoskeletal tumors. Materials and methods We reviewed the medical records and imaging studies of 56 patients who were suspected of having recurrent tumors following surgical resection and allograft replacement treatment for a variety of musculoskeletal neoplasms. The imaging modalities included radiographs, CT, and MRI. Results There were 47 cases of recurrent tumors. All tumor recurrences were in the soft tissues of the surgical bed (41 patients), or in the native bone adjacent to the host/allograft junction (6 patients). None of the recurrences originated in the allografts. Nine patients suspected of having recurrences were discovered to have non-neoplastic masses. Five of these were very closely related to the allograft, wrapping around parts of the allograft, and the other 4 were in the surgical bed, 2 of which were abscesses and two were seromas. Conclusion Most masses arising in the vicinity of allografts implanted following resection of musculoskeletal tumors represent recurrent neoplasms. A minority are reactive processes or abscesses or fluid collections. These "pseudoneoplasms," specifically those closely related to the allografts, have specific imaging characteristics that help distinguish them from recurrent tumors. C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthoped, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kattapuram, SV (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Yawkey 6036,55 Fruit St, Boston, MA 02114 USA. EM skattapuram@partners.org NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2007 VL 36 IS 8 BP 747 EP 753 DI 10.1007/s00256-007-0292-8 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 181YV UT WOS:000247473200006 PM 17415562 ER PT J AU Merkin, SS Roux, AVD Coresh, J Fried, LF Jackson, SA Powe, NR AF Merkin, Sharon Stein Roux, Ana V. Diez Coresh, Josef Fried, Linda F. Jackson, Sharon A. Powe, Neil R. TI Individual and neighborhood socioeconomic status and progressive chronic kidney disease in an elderly population: The Cardiovascular Health Study SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE socioeconomic; kidney disease; neighborhood; elderly; USA ID STAGE RENAL-DISEASE; RISK-FACTORS; ATHEROSCLEROSIS RISK; UNITED-STATES; MORTALITY SELECTION; EXPLANATORY FACTORS; MULTILEVEL ANALYSIS; PHYSICAL-ACTIVITY; SERUM CREATININE; ALAMEDA COUNTY AB Few studies have focused on the association between socioeconomic status (SES) and progressive chronic kidney disease (pCKD) in an elderly population. We conducted a cohort study of 4735 Cardiovascular Health Study participants, ages 65 and older and living in 4 US communities, to examine the independent risk of pCKD associated with income, education and living in a low SES area. pCKD was defined as creatinine elevation >= 0.4 mg/dL (35 mu mol/L) over a 4-7 year follow-up or CKD hospitalization. Area SES was characterized using measures of income, wealth, education and occupation for 1990 (corresponding to time of enrollment) US Census block groups of residence. Age and study site-adjusted incidence rates (per 1000 person years) of pCKD by quartiles of area-level SES score, income and education showed decreasing rates with increasing SES. Cox proportional hazards models showed that living in the lowest SES area quartile, as opposed to the highest, was associated with 50% greater risk of pCKD, after adjusting for age, gender, study site, baseline creatinine, and individual-level SES. This increased risk and trend persisted after adjusting for lifestyle risk factors, diabetes and hypertension. We found no significant independent associations between pCKD and individual-level income or education (after adjusting for all other SES factors). As such, living in a low SES area is associated with greater risk of pCKD in an elderly US population. (c) 2007 Elsevier Ltd. All rights reserved. C1 Welch Ctr Prevent Epidemiol & Clin Res, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Univ Michigan, Sch Publ Hlth, Dearborn, MI 48128 USA. Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. RP Merkin, SS (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Div Geriatr, Los Angeles, CA 90024 USA. EM smerkin@mednet.ucla.edu FU NIDDK NIH HHS [K24 DK002643, K24 DK02643]; NIMHD NIH HHS [P60 MD000206, P60 MD00206] NR 59 TC 68 Z9 68 U1 9 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD AUG PY 2007 VL 65 IS 4 BP 809 EP 821 DI 10.1016/j.socscimed.2007.04.011 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 203EA UT WOS:000248956700015 PM 17499411 ER PT J AU Rich, DQ Gaziano, JM Kurth, T AF Rich, David Q. Gaziano, J. Michael Kurth, Tobias TI Geographic patterns in overall and specific cardiovascular disease incidence in apparently healthy men in the United States SO STROKE LA English DT Article DE cardiovascular disease; epidemiology; ischemic stroke; myocardial infarction ID NUTRITION EXAMINATION SURVEY; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH; PHYSICIANS HEALTH; STROKE MORTALITY; SELENIUM LEVELS; SERUM SELENIUM; BETA-CAROTENE; RISK; REGION AB Background and Purpose - Residence in the Southeastern United States (US) has been linked to increased stroke incidence and mortality. However, data on regional variability in overall cardiovascular disease (CVD) and specific coronary heart disease incidence are sparse. Methods - We assessed the risk of major CVD (nonfatal stroke, nonfatal myocardial infarction, or death from CVD) and specific CVD associated with region of residence (Northeast, Southeast, Midwest, and West) in 17 927 apparently healthy male participants of the Physicians' Health Study. Subjects were aged 40 to 84, most were white (93%), and had no previous CVD at baseline. We used residence in the Northeast as the reference group and proportional hazards models to adjust for potential confounding. Results - We found no difference in risk of major CVD between regions of residence. Further, we found no consistent association between myocardial infarction and CVD death and region of residence. In contrast, we found a significantly increased risk of total stroke (HR, 1.22; 95% CI, 1.02 to 1.47) associated with residence in the Southeast compared with the Northeast. This relative risk was further increased for ischemic stroke (HR, 1.30; 95% CI, 1.06 to 1.58). We saw no difference in risk of any outcome when categorizing state of residence into tertiles based on mean winter temperature, mean summer temperature, or into 2 groups based on latitude. Conclusions - In this homogenous and well-characterized cohort of US male physicians, we found greater incidence of ischemic stroke, but not other vascular events among those living in the Southeastern US, compared with other regions. C1 Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02120 USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Epidemiol, Piscataway, NJ 08854 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Kurth, T (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA 34944, CA 40360, R01 CA097193]; NHLBI NIH HHS [HL 26490, HL 34595] NR 23 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2007 VL 38 IS 8 BP 2221 EP 2227 DI 10.1161/STROKEAHA.107.483719 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 196AY UT WOS:000248455100007 PM 17600228 ER PT J AU Ng, YS Stein, J Ning, M Black-Schaffer, RM AF Ng, Yee Sien Stein, Joel Ning, MingMing Black-Schaffer, Randie M. TI Comparison of clinical characteristics and functional outcomes of ischemic stroke in different vascular territories SO STROKE LA English DT Article DE cerebral infarct; functional outcomes; rehabilitation; vascular territory ID CEREBRAL-ARTERY TERRITORY; LENGTH-OF-STAY; RESOURCE USE; HUMAN BRAIN; REHABILITATION; REGISTRY; INFARCTION; RECOVERY; PATTERNS; PROGNOSIS AB Background and Purpose - We aim to compare demographics and functional outcomes of patients with stroke in a variety of vascular territories who underwent inpatient rehabilitation. Such comparative data are important in functional prognostication, rehabilitation, and healthcare planning, but literature is scarce and isolated. Methods - Using data collected prospectively over a 9-year period, we studied 2213 individuals who sustained first-ever ischemic strokes and were admitted to an inpatient stroke rehabilitation program. Strokes were divided into anterior cerebral artery, middle cerebral artery (MCA), posterior cerebral artery, brain stem, cerebellar, small-vessel strokes, and strokes occurring in more than one vascular territory. The main functional outcome measure was the Functional Independence Measure (FIM). Repeated-measures analysis of covariance with post hoc analyses was used to compare functional outcomes of the stroke groups. Results - The most common stroke groups were MCA stroke (50.8%) and small-vessel stroke (12.8%). After adjustments for age, gender, risk factors, and admission year, the stroke groups can be arranged from most to least severe disability on admission: strokes in more than one vascular territory, MCA, anterior cerebral artery, posterior cerebral artery, brain stem, cerebellar, and small-vessel strokes. The sequence was similar on discharge, except cerebellar strokes had the least disability rather than small-vessel strokes. Hemispheric (more than one vascular territory, MCA, anterior cerebral artery, posterior cerebral artery) strokes collectively have significantly lower admission and discharge total and cognitive FIM scores compared with the other stroke groups. MCA stroke had the lowest FIM efficiency and cerebellar stroke the highest. Regardless, patients with stroke made significant (P < 0.001) and approximately equal (P < 0.535) functional gains in all groups. Higher admission motor and cognitive FIM scores, longer rehabilitation stay, younger patients, lower number of medical complications, and a year of admission after 2000 were associated with higher discharge total FIM scores on multiple regression analysis. Conclusions - Patients with stroke made significant functional gains and should be offered rehabilitation regardless of stroke vascular territory. The initial functional status at admission, rather than the stroke subgroup, better predicts discharge functional outcomes postrehabilitation. C1 Singapore Gen Hosp, Dept Rehabil Med, Singapore 169608, Singapore. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Ng, YS (reprint author), Singapore Gen Hosp, Dept Rehabil Med, Outram Rd, Singapore 169608, Singapore. EM ng.yee.sien@sgh.com.sg FU NINDS NIH HHS [K23-NS051588, R21-NS052498] NR 24 TC 49 Z9 53 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2007 VL 38 IS 8 BP 2309 EP 2314 DI 10.1161/STROKEAHA.106.475483 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 196AY UT WOS:000248455100022 PM 17615368 ER PT J AU Zhang, F Wang, SP Signore, AP Chen, J AF Zhang, Feng Wang, Suping Signore, Armando P. Chen, Jun TI Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia SO STROKE LA English DT Article DE brain ischemia; extracellular signal-related kinase 1/2; leptin; oxygen-glucose deprivation ID ERYTHROPOIETIN PROTECTS; IN-VIVO; BRAIN; ACTIVATION; APOPTOSIS; PATHWAY; CONTRIBUTES; RECEPTOR; NEURONS; KINASE AB Background and Purpose - Leptin is the major adipose hormone that regulates body weight and energy expenditure by activating leptin receptors in the hypothalamus. Leptin receptors are also present in other cell types, and a potent antiapoptotic effect for leptin has recently been reported. We investigated whether leptin was neuroprotective against ischemic brain injury. Methods - In vitro ischemic injury was induced in rat primary neuronal culture by oxygen-glucose deprivation for 90 minutes. In vivo ischemic brain injury was induced by middle cerebral artery occlusion in mice for 60 minutes. Results - Leptin receptors were detected in cultured rat cortical neurons, as well as in the mouse cortex, striatum, and hippocampus. In vitro results showed that leptin, 50 to 100 mu g/mL, protected primary cortical neurons against death induced by oxygen-glucose deprivation in a concentration-dependent manner. In vivo studies in the mouse brain demonstrated that the intraperitoneal administration of leptin, 2 to 8 mg/kg, dose-dependently reduced infarct volume induced by middle cerebral artery occlusion. Leptin was effective when injected 5 minutes before or 30 to 90 minutes after reperfusion, but not 2 hours after reperfusion. Leptin improved animal body weight recovery and behavioral parameters after cerebral ischemia. Leptin enhanced the phosphorylation of extracellular signal - related kinase 1/2. Both extracellular signal - related kinase 1/2 activation and neuroprotection were abolished by the administration of PD98059 in vitro and in vivo. Conclusions - Leptin is neuroprotective against ischemic neuronal injury. Our findings suggest that leptin is a legitimate candidate for the treatment of ischemic stroke. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu OI Zhang, Feng/0000-0001-7275-9989 FU NINDS NIH HHS [NS43802, NS36736, NS45048] NR 22 TC 98 Z9 106 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2007 VL 38 IS 8 BP 2329 EP 2336 DI 10.1161/STROKEAHA.107.482786 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 196AY UT WOS:000248455100025 PM 17600230 ER PT J AU Hodin, RA AF Hodin, Richard A. TI Gnothi se auton: SUS presidential address SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Gray 504, Boston, MA USA. EM rhodin@partners.org NR 1 TC 1 Z9 1 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 AUG PY 2007 VL 142 IS 2 BP 127 EP 135 DI 10.1016/j.surg.2007.04.006 PG 9 WC Surgery SC Surgery GA 198QE UT WOS:000248641800001 PM 17689676 ER PT J AU Ryon, M Pai, RD Sauer, JS Rattner, DW Thompson, CC AF Ryon, M. Pai, R. D. Sauer, J. S. Rattner, D. W. Thompson, C. C. TI Evaluating an optimal gastric closure method for transgastric surgery (vol 21, pg 677, 2007) SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Correction DE NOTES; transluminal; translumenal; transcolonic; transvaginal; access; transvisceral C1 Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. LSI Solut, Victor, NY 14564 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Dept Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM ccthompson@partners.org NR 1 TC 0 Z9 0 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 AUG PY 2007 VL 21 IS 8 BP 1472 EP 1472 DI 10.1007/s00464-007-9465-8 PG 1 WC Surgery SC Surgery GA 200BA UT WOS:000248737700046 ER PT J AU DeLaney, TF AF DeLaney, Thomas F. TI Clinical proton radiation therapy research at the Francis H. Burr Proton Therapy Center SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article; Proceedings Paper CT Symposium on Developing and Understanding a Hospital-based Proton Facility - Bringing Physics into Medicine CY OCT 18-20, 2006 CL Indian Wells, CA DE proton radiation therapy; clinical operations AB The Francis H. Burr Proton Therapy Center has a 230 MeV cyclotron from which proton beams are directed to two isocentric gantries, a stereotactic intracranial beam line, and an eye line. Because of improved physical dose distribution, proton radiotherapy allows dose escalation to improve local tumor control in anatomic sites and histologies where local control is suboptimal with photons. The improved dose localization also reduces normal-tissue doses with an anticipated reduction in acute and late toxicity. Clinical treatment protocols, developed to exploit the dosimetric advantages of protons over photons, have been grouped into two broad categories. In the first, dose is escalated for anatomic sites where local control with conventional radiation doses has been suboptimal. In the second, normal-tissue sparing with protons is designed to minimize acute and late toxicity. Treatment of patients on clinical research protocols has been encouraged. Patient treatments began on the first gantry in November 2001; on the eye line in April 2002; on the second gantry in May 2002; and on the stereotactic intracranial line in August 2006. The facility currently treats 60 patients per day, including up to six children daily under anesthesia. Dose-escalation studies have been completed for early stage prostate cancer (in conjunction with Loma Linda University) and sarcomas of the cervical spine/base of skull and thoracolumbosacral spine. Protocols are in progress or development for carcinoma of the nasopharynx, paranasal sinus carcinoma, non-small-cell lung carcinoma, locally advanced carcinoma of the prostate, hepatocellular carcinoma, and pancreatic cancer. Studies evaluating the use of protons for morbidity reduction include protocols for craniospinal irradiation in conjunction with systemic chemotherapy for medulloblastorna, retinoblastoma, pediatric rhabdomyosarcoma, other pediatric sarcomas, and accelerated, hypofractionated partial breast irradiation for T1NO breast carcinomas. For pediatric patients, protons have also been accepted as an alternative to photons for children enrolled in Children's Oncology Group (COG) protocols. Treatment of patients on these studies has often required the development of new treatment techniques (i.e., matching abutting fields for craniospinal irradiation), respiratory gating, and development of appropriate clinical infrastructure support (i.e., increase in availability of pediatric anesthesia) to allow appropriate treatment, In addition, a clinical research infrastructure for protocol development and data management is required. Results to date indicate that proton radiation therapy offers several potential treatment advantages to patients that can be studied in the setting of clinical trials. Patients' willingness to enter these clinical trials seems to be quite high; accrual to selected studies has been favorable. C1 Massachusetts Gen Hosp, Div Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Div Radiat Oncol, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org NR 7 TC 13 Z9 13 U1 0 U2 8 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD AUG PY 2007 VL 6 IS 4 SU S BP 61 EP 66 PG 6 WC Oncology SC Oncology GA 207VT UT WOS:000249279900010 PM 17668954 ER PT J AU Edd, JF Davalos, RV AF Edd, Jon F. Davalos, Rafael V. TI Mathematical Modeling of irreversible Electroporation for treatment planning SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE tumor ablation; complete regression; electric pulses; electropermeabilization; pulsed electric fields (PEFs); and cancer therapy ID ELECTRICAL-IMPEDANCE TOMOGRAPHY; IN-VIVO ELECTROPORATION; TISSUE ELECTROPORATION; THEORETICAL-ANALYSIS; FIELD DISTRIBUTION; SINGLE-CELL; ELECTROCHEMOTHERAPY; ABLATION; PULSES; MECHANISMS AB Irreversible Electroporation (IRE) is a new drug-free method to ablate undesirable tissue of particular use in cancer therapy. IRE achieves cell death within the targeted tissue through a series of electric pulses that elevate the transmembrane potentials to an extent that permanently damages the lipid bilayers throughout the treated region. Although the IRE procedure is easy to perform, treatment planning is complicated by the fact that the electric field distribution within the tissue, the greatest single factor controlling the extents of IRE, depends non-trivially on the electrode configuration, pulse parameters and any tissue heterogeneities. To address this difficulty, we instruct on how to properly model IRE and discuss the benefit of modeling in designing treatment protocols. The necessary theoretical basis is introduced and discussed through the detailed analysis of two classic dual-electrode configurations from electrochemotherapy: coaxial disk electrodes and parallel needle electrodes. Dimensionless figures for these cases are also provided that allow cell constants, treated areas, and the details of heating to be determined for a wide range of conditions, for uniform tissues, simply by plugging in the appropriate physical property values and pulse parameters such as electrode spacing, size, and pulse amplitude. Complexities, such as heterogeneous tissues and changes in conductivity due to electroporation, are also discussed. The synthesis of these details can be used directly by surgeons in treatment planning. Irreversible electroporation is a promising new technique to treat cancer in a targeted manner without the use of drugs; however, it does require a detailed understanding of how electric currents flow within biological tissues. By providing the understanding and tools necessary to design an IRE protocol, this study seeks to facilitate the translation of this new and exciting cancer therapy into clinical practice. C1 Wake Forest Univ, Virginia Tech, Sch Biomed Engn & Sci, Blacksburg, VA 24061 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Davalos, RV (reprint author), Wake Forest Univ, Virginia Tech, Sch Biomed Engn & Sci, Blacksburg, VA 24061 USA. EM davalos@vt.edu RI Davalos, Rafael/F-9012-2011; Sano, Michael/E-1715-2011 NR 47 TC 86 Z9 88 U1 1 U2 14 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD AUG PY 2007 VL 6 IS 4 BP 275 EP 286 PG 12 WC Oncology SC Oncology GA 204VV UT WOS:000249073000003 PM 17668934 ER PT J AU Venegas, J AF Venegas, Jose TI Linking ventilation heterogeneity and airway hyperresponsiveness in asthma SO THORAX LA English DT Editorial Material ID NITRIC-OXIDE; INDUCED BRONCHOCONSTRICTION; COMPUTED-TOMOGRAPHY; BRONCHOMOTOR TONE; CLOSURE; METHACHOLINE; TECHNEGAS; PATTERN AB Heterogeneity indices derived from the multiple breath nitrogen washout technique are strongly associated with AHR in asthma. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Venegas, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM jvenegas@partners.org FU NHLBI NIH HHS [R01 HL068011] NR 23 TC 10 Z9 10 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD AUG PY 2007 VL 62 IS 8 BP 653 EP 654 DI 10.1136/thx.2007.073239 PG 2 WC Respiratory System SC Respiratory System GA 199IQ UT WOS:000248689800001 PM 17687092 ER PT J AU Zhai, R Gong, MN Zhou, W Thompson, TB Kraft, P Su, L Christiani, DC AF Zhai, R. Gong, M. N. Zhou, W. Thompson, T. B. Kraft, P. Su, L. Christiani, D. C. TI Genotypes and haplotypes of the VEGF gene are associated with higher mortality and lower VEGF plasma levels in patients with ARDS SO THORAX LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; EPITHELIAL-CELLS; PULMONARY-EDEMA; POLYMORPHISMS; RISK; CANCER; SURVIVAL AB Background: Endothelial injury is an important prognostic factor in acute respiratory distress syndrome (ARDS). Vascular endothelial growth factor (VEGF) plays a critical role in endothelial destruction and angiogenesis. Genetic variations of the VEGF gene have been associated with VEGF production. A study was undertaken to investigate the impact of VEGF gene polymorphisms on the clinical outcomes of ARDS. Methods: Three VEGF polymorphisms (-460C/T, +405C/G and -936C/T) were determined in 1253 patients in an intensive care unit with risk factors for ARDS, 394 of whom developed ARDS. Patients were followed for assessment of 60 day survival. Plasma VEGF levels were measured in 71 patients with ARDS. Results: The +936TT (OR 4.29, 95% CI 1.12 to 16.40, p = 0.03) and +936CT+TT (OR 1.98, 95% CI 1.14 to 3.42, p = 0.01) genotypes were significantly associated with increased mortality from ARDS. Plasma VEGF levels in patients with ARDS with the +936CT+TT genotype were significantly lower than in subjects with the +936CC genotype (median 49 (IQR 16-98) pg/ml vs 112 (IQR 47-162) pg/ml, p = 0.02). At the haplotype level, haplotype TCT (-460T+405C+936T) was significantly associated with a higher rate of mortality (OR 2.89, 95% CI 1.30 to 6.43, p = 0.009) and haplotype CGT (-460C+405G+936T) was associated less strongly with increased mortality (OR 1.90, 95% CI 0.94 to 3.83, p = 0.07) in patients with ARDS. Lower plasma VEGF levels were correlated with the probability of haplotype CGT (coefficient = 20.26, p, 0.05), but the same trend of correlation was not significant to haplotype TCT. Conclusions: VEGF polymorphisms may contribute to the prognosis and inter-individual variations in circulating VEGF levels in patients with ARDS. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu FU NHLBI NIH HHS [K23 HL067197, HL60710, R01 HL060710, K23 HL67197]; NIEHS NIH HHS [ES00002, P30 ES000002] NR 33 TC 53 Z9 57 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD AUG PY 2007 VL 62 IS 8 BP 718 EP 722 DI 10.1136/thx.2006.069393 PG 5 WC Respiratory System SC Respiratory System GA 199IQ UT WOS:000248689800016 PM 17289863 ER PT J AU Goerge, T Kleineruschkamp, F Barg, A Schnaeker, EM Huck, V Schneider, MF Steinhoff, M Schneiderl, S AF Goerge, Tobias Kleinerueschkamp, Felix Barg, Alexej Schnaeker, Eva-Maria Huck, Volker Schneider, Matthias F. Steinhoff, Martin Schneiderl, StefanW. TI Microfluidic reveals generation of platelet-strings on tumor-activated endothelium SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE von Willebrand factor; platelet physiology; cancer; imaging ID VON-WILLEBRAND-FACTOR; CANCER; RECEPTOR AB Neoplastic diseases are often associated with thromboembolic events, however the precise mechanism underlying this observation is a matter of ongoing investigation. It is known that matrixmetalloproteinase- I (MMP-I) canonically activates the thrombin receptor (PAR-I) and we recently reported that highly metastatic tumor cells of melanoma and colon cancer are secreting matrixmetalloproteinase-I. This tumor-derived MMPI was shown to be a major activator of endothelial PAR-I, thus leading to endothelial cell activation. As tumor-induced thrombosis is a characteristic of metastazing tumors, we investigated whether tumor-derived supernatant (TUSN) from melanoma and colon cancer may induce adhesion of circulating platelets,an initial step in thrombus formation. A time-course study revealed that TU-SN induces a rapid secretion of von Willebrand factor (VWF) within minutes. Using a novel microfluidic device we analyzed platelet-enclothelial interactions in a closed circuit. Immunofluorescence imaging showed that TU-SN rapidly induces platelet-string formation via secreted VWF. We demonstrated that tumor-derived supernatant is a potent agonist inducing platelet adhesion under flow conditions. C1 Univ Munster, Dept Dermatol, D-4400 Munster, Germany. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Augsburg, Dept Biophys, D-8900 Augsburg, Germany. RP Goerge, T (reprint author), Univ Klinikum Munster, Dept Dermatol, Von Esmarchstr 58, D-48149 Munster, Germany. EM Tobias.Goerge@ukmuenster.de; sschnei@mednet.uni-muenster.de RI Steinhoff, Martin/F-6312-2013; OI Steinhoff, Martin/0000-0002-7090-2187 NR 14 TC 28 Z9 29 U1 0 U2 7 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 2007 VL 98 IS 2 BP 283 EP 286 DI 10.1160/TH07-03-0163 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 201BZ UT WOS:000248807800005 PM 17721608 ER PT J AU Borenstein, JT Weinberg, EJ Orrick, BK Sundback, C Kaazempur-Mofrad, MR Vacanti, JP AF Borenstein, Jeffrey T. Weinberg, Eli J. Orrick, Brian K. Sundback, Cathryn Kaazempur-Mofrad, Mohammad R. Vacanti, Joseph P. TI Microfabrication of three-dimensional engineered scaffolds SO TISSUE ENGINEERING LA English DT Review ID BIODEGRADABLE POLYMER; PEPTIDE SCAFFOLDS; PROGENITOR CELLS; TISSUE; FABRICATION; SURFACES; MICROFLUIDICS; TECHNOLOGY; MICROSCALE; CHANNELS AB One of the principal challenges facing the field of tissue engineering over the past 2 decades has been the requirement for large- scale engineered constructs comprising precisely organized cellular microenvironments. For vital organ assist and replacement devices, microfluidic- based systems such as the microcirculation, biliary, or renal filtration and resorption systems and other functional elements containing multiple cell types must be generated to provide for viable engineered tissues and clinical benefit. Over the last several years, microfabrication technology has emerged as a versatile and powerful approach for generating precisely engineered scaffolds for engineered tissues. Fabrication process tools such as photolithography, etching, molding, and lamination have been established for applications involving a range of biocompatible and biodegradable polymeric scaffolding materials. Computational fluid dynamic designs have been used to generate scaffold designs suitable for microvasculature and a number of organ-specific constructs; these designs have been translated into 3-dimensional scaffolding using microfabrication processes. Here a brief overview of the fundamental microfabrication technologies used for tissue engineering will be presented, along with a summary of progress in a number of applications, including the liver and kidney. C1 Charles Stark Draper Lab Inc, Ctr Biomed Engn, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. BioEngine Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. RP Borenstein, JT (reprint author), Charles Stark Draper Lab Inc, Ctr Biomed Engn, Mail Stop 37,555 Technol Sq, Cambridge, MA 02139 USA. EM jborenstein@draper.com NR 46 TC 129 Z9 131 U1 7 U2 51 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 AUG PY 2007 VL 13 IS 8 BP 1837 EP 1844 DI 10.1089/ten.2006.0156 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 200CT UT WOS:000248742200005 PM 17590149 ER PT J AU Ibusuki, S Halbesma, GJ Randolph, MA Redmond, RW Kochevar, IE Gill, TJ AF Ibusuki, Shinichi Halbesma, Gerrit J. Randolph, Mark A. Redmond, Robert W. Kochevar, Irene E. Gill, Thomas J. TI Photochemically cross-linked collagen gels as three-dimensional scaffolds for tissue engineering SO TISSUE ENGINEERING LA English DT Article ID MONOLAYER-CULTURE; ENDOTHELIAL-CELLS; LINKING; RIBOFLAVIN; CARTILAGE; MEMBRANES; INCISIONS; MODEL; UVA AB Collagen gels have many favorable attributes for tissue engineering, but the gels undergo dramatic contraction when cells are added because of the weak noncovalent bonds that form during spontaneous gelation. We hypothesized that photochemically cross- linking collagen gels would make suitable scaffolds for tissue engineering with favorable cell viability and minimal gel contraction. Rose Bengal and riboflavin were chosen as candidate photo- initiators for gel cross- linking using 532- and 458- nm- light wavelengths, respectively. Chondrocyte viability was measured after initial gelation for several concentrations of initiators. Cell viability and gel contraction were then measured using chondrocytes and fibroblasts over 7 days of culture. Rose Bengal used at concentrations necessary for gelation resulted in little or no cell viability. Short- term viability results showed that 0.25- or 0.5- mM concentrations of riboflavin, and 40 s of illumination permitted more than 90% cell viability. Using riboflavin concentrations of 0.25 or 0.5mM, long- term chondrocyte viability was 113.1 +/- 11.6% and 25.4 +/- 2.7%, respectively, at day 7. Although non- cross- linked chondrocyte constructs contracted to 59.9 +/- 11.8% of their original diameter and fibroblasts contracted to 24.9 +/- 5.0% of their original diameter by day 7, the cross- linked constructs retained 88.8 +/- 7.4% and 85.5 +/- 5.0% of the original diameter, respectively. In conclusion, by photochemically cross- linking collagen gels using riboflavin and visible light, stable gel scaffolds with favorable cell survival can be produced. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, WAC453,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org NR 23 TC 52 Z9 54 U1 6 U2 21 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 AUG PY 2007 VL 13 IS 8 BP 1995 EP 2001 DI 10.1089/ten.2006.0153 PG 7 WC Cell & Tissue Engineering SC Cell Biology GA 200CT UT WOS:000248742200015 PM 17518705 ER PT J AU Tolboom, H Pouw, R Uygun, K Tanimura, Y Izamis, ML Berthiaume, F Yarmush, ML AF Tolboom, Herman Pouw, Roos Uygun, Korkut Tanimura, Yoko Izamis, Maria-Louisa Berthiaume, Francois Yarmush, Martin L. TI A model for normothermic preservation of the rat liver SO TISSUE ENGINEERING LA English DT Article ID HEART-BEATING DONOR; COLD-STORAGE; MACHINE PERFUSION; DAMAGED KIDNEYS; ISCHEMIC-INJURY; WARM PERFUSION; EX-VIVO; TRANSPLANTATION; OXYGEN; SYSTEM AB YCurrent techniques for the preservation of donor livers typically rely on cold temperatures (similar to 0 - 4 degrees C) to slow down metabolic processes. Recently, normothermic extracorporeal liver perfusion ( NELP) has regained interest as a potentially promising approach for long- term liver preservation. Unlike cold- storage techniques, NELP attempts to maintain the liver in a near physiological environment, thus enabling normal metabolic and tissue repair processes to take place, which may help in the recovery of ischemically damaged and fatty donor livers, both of which represent significant untapped sources of donor livers. However, NELP is technically more complex than cold- storage techniques, and the lack of standardized small animal models limits its development. Here we describe a rat NELP system that is simple and costeffective to run. We show that rat livers that underwent NELP for 6 h could be routinely transplanted into syngeneic recipient rats with excellent 1- month survival. During perfusion, the release of cytosolic enzymes, bile and urea production, and oxygen uptake rate could be readily monitored, thus providing a comprehensive picture of hepatic function before transplantation. This system will help in the optimization of NELP in several ways, such as for the improvement of perfusion conditions and the development of quantitative metabolic criteria for hepatic viability. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org OI Pouw, Roos/0000-0002-4707-1186 FU NIDDK NIH HHS [R01 DK43371] NR 32 TC 22 Z9 23 U1 0 U2 3 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 AUG PY 2007 VL 13 IS 8 BP 2143 EP 2151 DI 10.1089/ten.2007.0101 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 200CT UT WOS:000248742200029 PM 17596120 ER PT J AU Dzik, S AF Dzik, Sunny TI Radio frequency identification for prevention of bedside errors SO TRANSFUSION LA English DT Article; Proceedings Paper CT 2nd Joint Conference of Americas Blood Centers/European-Blood-Alliance CY NOV 13-14, 2006 CL London, ENGLAND SP European Blood Alliance C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 20 Z9 21 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2007 VL 47 IS 2 SU S BP 125S EP 129S DI 10.1111/j.1537-2995.2007.01367.x PG 5 WC Hematology SC Hematology GA 199HD UT WOS:000248685900008 PM 17651335 ER PT J AU Dzik, S AF Dzik, Sunny TI Use of a computer-assisted system for blood utilization review SO TRANSFUSION LA English DT Article; Proceedings Paper CT 2nd Joint Conference of Americas Blood Centers/European-Blood-Alliance CY NOV 13-14, 2006 CL London, ENGLAND SP European Blood Alliance C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Dzik, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 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 AUG PY 2007 VL 47 IS 2 SU S BP 142S EP 144S DI 10.1111/j.1537-2995.2007.01371.x PG 3 WC Hematology SC Hematology GA 199HD UT WOS:000248685900012 PM 17651338 ER PT J AU Hu, H Djuretic, I Sundrud, MS Rao, A AF Hu, Hui Djuretic, Ivana Sundrud, Mark S. Rao, Anjana TI Transcriptional partners in regulatory T cells: Foxp3, Runx and NFAT SO TRENDS IN IMMUNOLOGY LA English DT Article ID DIFFERENTIATION; TOLERANCE; PROTEINS; PROMOTER; MICE AB A general theme in gene regulation is that transcription factors never function alone. Recent studies have emphasized this concept for regulatory T cells, a unique lineage of CD4(+) T cells that exert active immune suppression and are essential to maintaining self-tolerance. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM arao@ebr.med.har-vard.edu NR 28 TC 35 Z9 38 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD AUG PY 2007 VL 28 IS 8 BP 329 EP 332 DI 10.1016/j.it.2007.06.006 PG 4 WC Immunology SC Immunology GA 202DZ UT WOS:000248883500001 PM 17618833 ER PT J AU Goldfeld, A Ellner, JJ AF Goldfeld, Anne Ellner, Jerrold J. TI Pathogenesis and management of HIV/TB co-infection in Asia SO TUBERCULOSIS LA English DT Article; Proceedings Paper CT 10th International Conference on Emerging Infectious Diseases in the Pacific Rim CY DEC 07-10, 2004 CL kyoto, JAPAN SP US-Japan Cooperat Med Sci Program DE TB-HIV; atypical forms; Vietnam; integrated control and research programs in Cambodia ID ACTIVE ANTIRETROVIRAL THERAPY; ISONIAZID PREVENTIVE THERAPY; PULMONARY TUBERCULOSIS; INFECTED PATIENTS; CAMBODIA; RIFAMPICIN; EFFICACY; AFRICA; COHORT; CELLS AB HIV infection increases the risk of reactivation of latent tuberculosis (TB), progression of a new infection or re-infection to active disease, and acceleration of the natural course of the disease with a more rapid spread of strains, including those that are drug resistant, in the community. TB also accelerates the course of HIV-induced disease by activating viral replication and accentuating the decline in CD4 T cell counts. In this chapter, TB-HIV coinfection is discussed in the context of the situation in Vietnam, particularly Ho Chi Minh City, the creation of a well-integrated TB control and research programs in Cambodia, and the broad principles of the co-management of TB/HIV particularly in the context of the associated atypical forms of pulmonary TB (PTB), increased non-PTB and the frequency of acid fast smear negative cases. (c) 2007 Published by Elsevier Ltd. C1 CBR Inst, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Ellner, JJ (reprint author), CBR Inst, Cambridge, MA USA. EM jerroldellner@yahoo.com NR 30 TC 13 Z9 14 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD AUG PY 2007 VL 87 SU 1 BP S26 EP S30 DI 10.1016/j.tube.2007.05.003 PG 5 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 216OR UT WOS:000249888400007 PM 17606407 ER PT J AU Nguyen, PL Chen, MH Renshaw, AA Sussman, B D'Amico, AV AF Nguyen, Paul L. Chen, Ming-Hui Renshaw, Andrew A. Sussman, Brenda D'Amico, Anthony V. TI Effect of definition of preradiotherapy prostate-specific antigen velocity on its association with prostate cancer-specific mortality and all-cause mortality SO UROLOGY LA English DT Article ID PREOPERATIVE PSA VELOCITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; DOUBLING TIME; RISK; SURVIVAL; PREDICTORS; DEATH AB OBJECTIVES An increasing prostate-specific antigen (PSA) velocity (PSAV) is associated with a shorter time to prostate cancer-specific mortality (PCSM) after definitive local therapy. This study examined the effect on this association when the PSAV was estimated using all PSA values (PSAV-all) instead of the PSA values within 18 months before diagnosis (PSAV-18). METHODS We studied 358 men (median age 71.2) with clinically localized prostate cancer treated with external beam radiotherapy to a dose of 70.35 Gy from 1989 to 2002. The median follow-up was 4.0 years. The Cox and Gray's multivariate regression analyses were used to evaluate the association between PSAV and the interval to PSA recurrence, all-cause mortality, and PCSM, adjusting for known prognostic factors. RESULTS The median PSAV-18 and PSAV-all was 1.50 ng/mL/yr (interquartile range 0.74 to 3.82) and 1.20 ng/mL/yr (interquartile range 0.69 to 3.34), respecrively. Of the 358 men, 226 (63%) had only two PSA values; therefore, the estimation of their PSAV was the same, irrespective of the method used. Remarkably, despite the identical estimates for PSAV in 63% of the men in this study, after adjusting for known prognostic factors, the hazard ratios describing the significant associations with the interval to PSA recurrence, PCSN4, and all-cause mortality increased and the associated P values decreased using PSAV-18 compared with PSAV-all. CONCLUSIONS The results of this study have shown that the PSAV estimated using the pretreatment PSA values obtained approximately 18 months before diagnosis compared with using all previous PSA values provides a stronger association with the interval to PSA recurrence, PCSM, and all-cause mortality after RT. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Miami Baptist Hosp, Dept Pathol, Miami, FL USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 15 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 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2007 VL 70 IS 2 BP 288 EP 293 DI 10.1016/j.urology.2007.03.061 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 211WV UT WOS:000249554900019 PM 17826491 ER PT J AU Smith, MR Cook, RJ Coleman, R Brown, J Lipton, A Major, P Hei, YJ Saad, F AF Smith, Matthew R. Cook, Richard J. Coleman, Robert Brown, Janet Lipton, Allan Major, Pierre Hei, Yong Jiang Saad, Fred TI Predictors of skeletal complications in men with hormone-refractory metastatic prostate cancer SO UROLOGY LA English DT Article ID BONE TURNOVER; ZOLEDRONIC ACID; SURVIVAL; MARKERS; CARCINOMA; DISEASE; PAIN AB OBJECTIVES Skeletal complications are a major cause of morbidity in men with hormone-refractory metastatic prostate cancer. These analyses were designed to identify the variables associated with a greater risk of skeletal complications. METHODS The 643 subjects in this report were participants in a randomized placebo-controlted trial to evaluate the effects of zoledronic acid on the incidence of skeletal-related events. All subjects had bone metastases and disease progression despite medical or surgical castration. The relationships between the baseline covariates and the time to the first skeletal-related event were assessed by Cox proportional hazard analyses. The serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide level was assessed as a representative specific marker of osteoblastic and osteoclastic activity, respectively. The other covariates included in the model were age, cancer duration, Eastern Cooperative Oncology Group performance status, analgesic use, and prostate-specific antigen, hemoglobin, and lactate dehydrogenase levels. RESULTS Elevated BAP levels were consistently associated with a greater risk of adverse skeletal outcomes. Elevated BAP was significantly associated with a shorter time to the first sketetal-related event on multivariate analyses of the entire study population (relative risk 1.84, 95% confidence interval 1.40 to 2.43; P < 0.001) and in subset analyses of the placebo and zoledronic acid groups. Elevated BAP levels were also consistently associated with adverse skeletal outcomes on multivariate analyses of the time to radiotherapy and pathologic fracture, the most common types of sketetal-retated events in the study population. No other baseline variable was consistently associated with the risk of adverse skeletal outcomes. CONCLUSIONS The results of our study have shown that elevated serum BAP levels are associated with a greater risk of adverse skeletal outcomes in men with hormone- refractory prostate cancer and bone metastases. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. Weston Park Hosp, Acad Unit Clin Oncon, Sheffield, S Yorkshire, England. Penn State Univ Hosp, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. McMaster Univ, Hamilton Reg Canc Ctr, Hamilton, ON, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. Nova Pharmaceut Corp, E Hanover, NJ USA. Univ Montreal, Hop Notre Dame, Ctr Hosp, Montreal, PQ, Canada. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990, K24 CA121990-02] NR 19 TC 38 Z9 38 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 AUG PY 2007 VL 70 IS 2 BP 315 EP 319 DI 10.1016/j.urology.2007.03.071 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 211WV UT WOS:000249554900024 PM 17826496 ER PT J AU Alexander, BM Chen, MH Carroll, P D'Amico, AV AF Alexander, Brian M. Chen, Ming-Hui Carroll, Peter D'Amico, Anthony V. TI Prostate-specific antigen level at initiation of hormonal therapy after prostate-specific antigen failure following prostatectomy or radiotherapy and therapeutic response SO UROLOGY LA English DT Article ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; MITOXANTRONE; PREDNISONE; DOCETAXEL AB OBJECTIVES To determine the pretreatment factors associated with an undetectable prostate -specific antigen (PSA) nadir after 8 months of androgen suppression therapy (AST). METHODS The study cohort comprised 137 men with an increasing PSA level after surgery or radiotherapy performed for localized prostate cancer who had undergone AST. Cox regression multivariate analyses were used to identify the factors associated with a PSA nadir of 0.2 ng/mL or less 8 months after AST initiation. RESULTS The PSA level at the initiation of AST was associated with a PSA nadir of 0.2 ng/mL or less after 8 months of AST, as both a continuous variable (adjusted odds ratio [OR] 0.44, P = 0.0001) and a categorical variable, with PSA greater than 10 ng/mL (OR 0.16, P = 0.007). The percentage of patients with a PSA nadir of 0.2 ng/mL or less was 86%, 72%, 75%, 67%, and 25% for men with a PSA level at the initiation of AST of 4 ng/mL or less, greater than 4 to 10 ng/mL, greater than 10 to 20 ng/mL, greater than 20 to 50 ng/mL, and greater than 50 ng/mL, respectively. CONCLUSIONS An elevated PSA level before the initiation of AST was significantly associated with a decreased chance of a PSA nadir of 0.2 ng/mL or less after 8 months of AST. Given the association between the PSA nadir after AST and prostate-cancer specific mortality, men with increasing PSA levels could be considered for Phase 11 and III clinical trials evaluating the effect of adding novel systemic therapies to AST on the interval to prostate-cancer specific mortality. C1 Harvard Radiat Oncol Program, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Alexander, BM (reprint author), Harvard Radiat Oncol Program, 375 Longwood Ave, Boston, MA 02115 USA. EM bmalexandeir@partners.org NR 13 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 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2007 VL 70 IS 2 BP 320 EP 323 DI 10.1016/j.urology.2007.03.074 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 211WV UT WOS:000249554900025 PM 17826497 ER PT J AU Etit, D Pilch, BZ Osgood, R Faquin, WC AF Etit, Demet Pilch, Ben Z. Osgood, Rebecca Faquin, William C. TI Fine-needle aspiration biopsy findings in sclerosing polycystic adenosis of the parotid gland SO VIRCHOWS ARCHIV LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 AUG PY 2007 VL 451 IS 2 BP 283 EP 284 PG 2 WC Pathology SC Pathology GA 210KH UT WOS:000249454600514 ER PT J AU Micev, M Todorovic, V Drndarevic, N Micev, MC Mitrovic, O Krsmanovic, M Pesko, P Heinrich, M AF Micev, Marjan Todorovic, Vera Drndarevic, Neda Micev, Milena Cosic Mitrovic, Olivera Krsmanovic, Mila Pesko, Predrag Heinrich, Michael TI Prognostic implications of immunoexpression of cell cycle regulatory proteins in gastrointestinal stromal tumours SO VIRCHOWS ARCHIV LA English DT Meeting Abstract C1 Clin Ctr Serbia, Inst Digest Dis, Belgrade, Serbia. Univ Belgrade, Med Res Inst, Belgrade, Serbia. Oregon Hlth & Sci Univ, Dept Med, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 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 AUG PY 2007 VL 451 IS 2 MA PP2-85 BP 315 EP 315 PG 1 WC Pathology SC Pathology GA 210KH UT WOS:000249454600613 ER PT J AU Amstalden, E Preffer, F Rosenberg, A AF Amstalden, Eliane Preffer, Frederic Rosenberg, Andrew TI Fibromatosis-primary and first recurrent tumors. A flow cytometric and clinical analysis in search to predictors of outcome SO VIRCHOWS ARCHIV LA English DT Meeting Abstract C1 Univ Estadual Campinas, Campinas, SP, Brazil. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD AUG PY 2007 VL 451 IS 2 BP 476 EP 476 PG 1 WC Pathology SC Pathology GA 210KH UT WOS:000249454601117 ER EF