FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ketas, TJ Kuhmann, SE Palmer, A Zurita, J He, WJ Ahuja, SK Klasse, PJ Moore, JP AF Ketas, Thomas J. Kuhmann, Shawn E. Palmer, Ashley Zurita, Juan He, Weijing Ahuja, Sunil K. Klasse, Per Johan Moore, John P. TI Cell surface expression of CCR5 and other host factors influence the inhibition of HIV-1 infection of human lymphocytes by CCR5 ligands SO VIROLOGY LA English DT Article DE CCR5 inhibitor; viral entry; IC50; receptor density ID HUMAN-IMMUNODEFICIENCY-VIRUS; SMALL-MOLECULE INHIBITORS; SHORT-TERM MONOTHERAPY; ENTRY INHIBITORS; ANTIVIRAL ACTIVITY; TYPE-1 INFECTION; DISEASE PROGRESSION; CORECEPTOR USAGE; RECEPTOR DENSITY; TROPIC HIV-1 AB Several CCR5 ligands, including small molecules and monoclonal antibodies (MAbs), are being developed as therapies for infection with strains of human immunodeficiency virus type I (HIV-1) that use CCR5 for entry (R5 viruses). The efficacy of such therapies could be influenced by inter-individual differences in host factors, such as CCR5 expression levels. To study this, we used peripheral blood mononuclear cells (PBMCs) from humans and rhesus macaques. The half-maximal inhibitory concentrations (IC50) of the small-molecule CCR5 ligands CMPD 167, UK427,857 and SCH-D, and of the PRO 140 MAb, differ by > 2 logs in a donor-dependent manner. We studied this variation by using flow cytometry to measure CCR5 expression on PBMCs from six of the human donors: the IC50 values of both SCH-D and PRO 140 correlated with CCR5 expression (R-2=0.64 and 0.99, respectively). We also determined the efficacy of the CCR5 ligands against HIV-1 infection of HeLa-derived cell lines that express CD4 at the same level but vary 2-fold in CCR5 expression (JC.48 and JC.53 cells). The moderately greater CCR5 expression on the JC.53 than the JC.48 cells was associated with proportionately higher median IC50 values for a] I four CCR5 ligands but not for a soluble CD4-based inhibitor or a non-nucleoside reverse transcriptase inhibitor. We conclude that differences in CCR5 expression on human PBMCs, which can be affected by CCL3L1 gene dose, may influence the antiviral potency of CCR5 ligands in vitro, but other host factors are also likely to be involved. These host factors may affect the clinical activity of CCR5 inhibitors, including their use as topical microbicides to prevent HIV-1 transmission. (c) 2007 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Univ Texas, Hlth Sci Ctr San Antonio, Vet Adm Res Ctr AIDS & HIV I Infect, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78285 USA. RP Moore, JP (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave,Box 62, New York, NY 10021 USA. EM jpm2003@mail.med.cornell.edu FU NIAID NIH HHS [AI46326, AI65413, AI66329, R01 AI041420, R01 AI041420-12, R01 AI046326, R21 AI046326, R37 AI046326, U19 AI065413, U19 AI065413-02, U19 AI066329, AI41420] NR 55 TC 46 Z9 46 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 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 2007 VL 364 IS 2 BP 281 EP 290 DI 10.1016/j.virol.2007.02.022 PG 10 WC Virology SC Virology GA 181FW UT WOS:000247423500004 PM 17428518 ER PT J AU Dore, GJ Torriani, FJ Rodriguez-Torres, M Brau, N Sulkowski, M Lamoglia, RS Tural, C Clumeck, N Nelson, MR Mendes-Correa, MC Godofsky, EW Dieterich, DT Yetzer, E Lissen, E Cooper, DA AF Dore, Gregory J. Torriani, Francesca J. Rodriguez-Torres, Maribel Brau, Norber Sulkowski, Mark Sola Lamoglia, Ricard Tural, Cristina Clumeck, Nathan Nelson, Mark R. Mendes-Correa, Maria C. Godofsky, Eliot W. Dieterich, Douglas T. Yetzer, Ellen Lissen, Eduardo Cooper, David A. TI Baseline factors prognostic of sustained virological response in patients with HIV-hepatitis C virus co-infection SO AIDS LA English DT Article DE APRICOT; co-infection; hepatitis C virus; sustained virological response ID ALPHA-2A PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; INFECTED PATIENTS; PEGYLATED INTERFERON-ALPHA-2B; THERAPY AB Objective: To identify baseline characteristics predictive of a sustained virological response (SVR) in patients with HIV-hepatitis C virus (HCV) co-infection treated with interferon-based therapy. Design/methods: A stepwise multiple logistic regression analysis was used to explore the prognostic factors associated with SVR [undetectable HCV-RNA (< 50 IU/ml) at the end of untreated follow-up in week 72]. Results: In all patients (n = 853), in addition to the HCV therapy received, the factors most predictive of SVR were baseline HCV-RNA [<= versus > 400 000 IU/ml; odds ratio (OR) 4.77; 95% confidence interval (CI) 3.15-7.22; P < 0.0001] and HCV genotype (OR 2.87; 95% CI 2.00-4.12; P < 0.0001). HIV treatment (with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor; P=0.034), race (P=0.027), and body mass index (P=0.039) were also weak predictors of HCV treatment response. Conclusions: In the AIDS PEGASYS Ribavirin International Co-infection Trial (APRICOT), the predictors of SVR among HIV-HCV co-infected patients treated with peginterferon alfa-2a plus ribavirin were similar to those in patients with HCV mono-infection. The HCV genotype and pretreatment HCV-RNA level had the greatest influence on SVR. (c) 2007 Lippincott Williams & Wilkins. C1 Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. St Vincent Hosp, Darlinghurst, NSW, Australia. Univ Calif San Diego, La Jolla, CA 92093 USA. Fdn Invest Diego, Santurce, PR USA. Ponce Sch Med, Santurce, PR USA. Bronx Vet Adm Med Ctr, New York, NY USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Autonomous Univ Barcelona, Hosp del Mar, E-08193 Barcelona, Spain. Hosp Univ Germans Trias & Pujol, Barcelona, Spain. Hop Univ St Pierre, Brussels, Belgium. Chelsea & Westminister Hosp, London, England. Univ Sao Paulo, Hosp Das Clin, BR-05508 Sao Paulo, Brazil. Bach & Godofsky, Bradenton, FL USA. Mt Sinai Sch Med, New York, NY USA. Roche, Nutley, NJ USA. Virgen Rocio Univ Hosp, Seville, Spain. RP Dore, GJ (reprint author), Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Level 2,376 Victoria St, Darlinghurst, NSW 2010, Australia. EM gdore@nchecr.unsw.edu.au RI mendes correa, maria cassia /A-6779-2013 NR 18 TC 31 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 31 PY 2007 VL 21 IS 12 BP 1555 EP 1559 DI 10.1097/QAD.0b013e328216f2c7 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 196PV UT WOS:000248495400008 PM 17630550 ER PT J AU Joy, T Keogh, HM Hadigan, C Lee, H Dolan, SE Fitch, K Liebau, J Lo, J Johnsen, S Hubbard, J Anderson, EJ Grinspoon, S AF Joy, Tisha Keogh, Hester M. Hadigan, Colleen Lee, Hang Dolan, Sara E. Fitch, Kathleen Liebau, James Lo, Janet Johnsen, Stine Hubbard, Jane Anderson, Ellen J. Grinspoon, Steven TI Dietary fat intake and relationship to serum lipid levels in HIV-infected patients with metabolic abnormalities in the HAART era SO AIDS LA English DT Article DE HIV; hypertriglyceridemia; metabolic abnormalities; nutrition; saturated fat ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CORONARY-HEART-DISEASE; PROTEASE INHIBITOR THERAPY; RESTING ENERGY-EXPENDITURE; LIPODYSTROPHY SYNDROME; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; INSULIN-RESISTANCE; BODY-COMPOSITION AB Objective: To evaluate dietary intake and its relationship to lipid parameters in HIV-infected patients with metabolic abnormalities. Method: We prospectively determined dietary intake (4-day food records or 24-h recall) in 356 HIV-infected patients and 162 community-derived HIV-negative controls evaluated for metabolic studies between 1998-2005. Differences in dietary intake between HIV-infected patients and non-HIV-infected controls, in relation to the established 2005 USDA (United States Department of Agriculture) Recommended Dietary Guidelines, were determined. The relationship between dietary fat intake and serum lipid levels among HIV-infected individuals was also evaluated. Results: Assessment of dietary intake in this group of HIV-infected patients demonstrated increased intake of total dietary fat (P < 0.05), saturated fat (P=0.006), and cholesterol (P=0.006) as well as a greater percentage of calories from saturated fat (P=0.002) and from trans fat (P=0.02), despite similar caloric intake to the control individuals. A significantly higher percentage of HIV-infected patients were above the 2005 USDA Recommended Dietary Guidelines for saturated fat (> 10%/day) (76.0% HIV vs. 60.9% controls, P=0.003), and cholesterol (> 300 mg/day) (49.7% HIV vs. 37.9% controls, P=0.04). Saturated fat intake was strongly associated with triglycericle level [triglyceride level increased 8.7 mg/dl (parameter estimate) per gram of increased saturated fat intake, P=0.005] whereas total fat was inversely associated with triglyceride level [triglycericle level decreased 3.0 mg/dl (parameter estimate) per gram of increased total fat intake, P=0.02] among HIV-infected individuals. Conclusions: Increased intake of saturated fat is seen and contributes to hypertrigly-ceridemia among HIV-infected patients who have developed metabolic abnormalities. Increased saturated fat intake should be targeted for dietary modification in this population. (c) 2007 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Program Nutr Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Med, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR001066, M01 RR 01066]; NICHD NIH HHS [T32 HD052961, T32 HD 052961]; NIDDK NIH HHS [R01 DK 49302, P30 DK040561, P30 DK040561-12, DK 02844, K23 DK002844, R01 DK059535] NR 52 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 31 PY 2007 VL 21 IS 12 BP 1591 EP 1600 DI 10.1097/QAD.0b013e32823644ff PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 196PV UT WOS:000248495400012 PM 17630554 ER PT J AU Dhingra, R Sullivan, L Jacques, PF Wang, TJ Fox, CS Meigs, JB D'Agostino, RB Gaziano, JM Vasan, RS AF Dhingra, Ravi Sullivan, Lisa Jacques, Paul F. Wang, Thomas J. Fox, Caroline S. Meigs, James B. D'Agostino, Ralph B. Gaziano, J. Michael Vasan, Ramachandran S. TI Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community SO CIRCULATION LA English DT Article DE diabetes mellitus; metabolic syndrome; epidemiology; obesity; risk factors; carbonated beverages ID FOOD FREQUENCY QUESTIONNAIRE; TYPE-2 DIABETES-MELLITUS; WEIGHT-GAIN; CARDIOVASCULAR-DISEASE; BEVERAGE CONSUMPTION; SWEETENED BEVERAGES; INSULIN-RESISTANCE; CHILDHOOD OBESITY; SUGAR; FRUCTOSE AB Background - Consumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals. Methods and Results - We related the incidence of metabolic syndrome and its components to soft drink consumption in participants in the Framingham Heart Study (6039 person-observations, 3470 in women; mean age 52.9 years) who were free of baseline metabolic syndrome. Metabolic syndrome was defined as the presence of >= 3 of the following: waist circumference >= 35 inches (women) or >= 40 inches ( men); fasting blood glucose >= 100 mg/dL; serum triglycerides >= 150 mg/dL; blood pressure >= 135/85 mm Hg; and high-density lipoprotein cholesterol < 40 mg/dL ( men) or < 50 mg/dL ( women). Multivariable models included adjustments for age, sex, physical activity, smoking, dietary intake of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Cross-sectionally, individuals consuming >= 1 soft drink per day had a higher prevalence of metabolic syndrome ( odds ratio [ OR], 1.48; 95% CI, 1.30 to 1.69) than those consuming < 1 drink per day. On follow-up ( mean of 4 years), new-onset metabolic syndrome developed in 765 ( 18.7%) of 4095 participants consuming < 1 drink per day and in 474 (22.6%) of 2059 persons consuming >= 1 soft drink per day. Consumption of >= 1 soft drink per day was associated with increased odds of developing metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74), obesity ( OR, 1.31; 95% CI, 1.02 to 1.68), increased waist circumference (OR, 1.30; 95% CI, 1.09 to 1.56), impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48), higher blood pressure ( OR, 1.18; 95% CI, 0.96 to 1.44), hypertriglyceridemia (OR, 1.25; 95% CI, 1.04 to 1.51), and low high-density lipoprotein cholesterol (OR, 1.32; 95% CI 1.06 to 1.64). Conclusions - In middle-aged adults, soft drink consumption is associated with a higher prevalence and incidence of multiple metabolic risk factors. C1 VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Duv Aging, Boston, MA 02115 USA. Alice Peck Day Mem Hosp, Lebanon, NH USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Tufts Univ, Nutr Res Ctr Aging, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Natl Heart Lung & blood Inst, Bethesda, MD USA. Brigham & Womens Hosp, Div Prevent Med & Cardiovasc Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU NCI NIH HHS [R01 CA097193]; NHLBI NIH HHS [1R01HL67288, 2K24HL04334, K23HL74077, N01-HC-25195] NR 43 TC 395 Z9 405 U1 9 U2 78 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 31 PY 2007 VL 116 IS 5 BP 480 EP 488 DI 10.1161/CIRCULATIONAHA.107.689935 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 196BG UT WOS:000248456000005 PM 17646581 ER PT J AU Neilan, TG Blake, SL Ichinose, F Raher, MJ Buys, ES Jassal, DS Furutani, E Perez-Sanz, TM Graveline, A Janssens, SP Picard, MH Scherrer-Crosbie, M Bloch, KD AF Neilan, Tomas G. Blake, Sarah L. Ichinose, Fumito Raher, Michael J. Buys, Emmanuel S. Jassal, Davinder S. Furutani, Elissa Perez-Sanz, Teresa Miriam Graveline, Amanda Janssens, Stefan P. Picard, Michael H. Scherrer-Crosbie, Marielle Bloch, Kenneth D. TI Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin SO CIRCULATION LA English DT Article DE cardiomyopathy; free radicals; heart failure; nitric oxide; nitric oxide synthase ID NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; INDUCED CARDIOTOXICITY; ENDOTHELIAL-CELLS; INDUCED APOPTOSIS; TRANSGENIC MICE; SUPEROXIDE GENERATION; REACTIVE OXYGEN; ADRIAMYCIN; OVEREXPRESSION AB Background - Flavoprotein reductases are involved in the generation of reactive oxygen species by doxorubicin. The objective of the present study was to determine whether or not one flavoprotein reductase, endothelial nitric oxide synthase (nitric oxide synthase 3 [NOS3]), contributes to the cardiac dysfunction and injury seen after the administration of doxorubicin. Methods and Results - A single dose of doxorubicin ( 20 mg/kg) was administered to wild-type (WT) mice, NOS3-deficient mice ( NOS3(-/-)), and mice with cardiomyocyte-specific overexpression of NOS3 (NOS3-TG). Cardiac function was assessed after 5 days with the use of echocardiography. Doxorubicin decreased left ventricular fractional shortening from 57 +/- 2% to 47 +/- 1% (P < 0.001) in WT mice. Compared with WT mice, fractional shortening was greater in NOS3(-/-) and less in NOS3-TG after doxorubicin (55 +/- 1% and 35 +/- 2%; P < 0.001 for both). Cardiac tissue was harvested from additional mice at 24 hours after doxorubicin administration for measurement of cell death and reactive oxygen species production. Doxorubicin induced cardiac cell death and reactive oxygen species production in WT mice, effects that were attenuated in NOS3(-/-) and were more marked in NOS3-TG mice. Finally, WT and NOS3(-/-) mice were treated with a lower dose of doxorubicin (4 mg/kg) administered weekly over 5 weeks. Sixteen weeks after beginning doxorubicin treatment, fractional shortening was greater in NOS3(-/-) than in WT mice ( 45 +/- 2% versus 28 +/- 1%; P < 0.001), and mortality was reduced (7% versus 60%; P < 0.001). Conclusions - These findings implicate NOS3 as a key mediator in the development of left ventricular dysfunction after administration of doxorubicin. C1 Massachusetts Gen Hosp, Div Carcinogenesis, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiol Div, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiol Div, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Leuven, Univ Hosp Gasthuisberg, Cardiol Div, Flanders Interuniv Inst Biotechnol,Ctr Transgene, Louvain, Belgium. RP Neilan, TG (reprint author), Massachusetts Gen Hosp, Div Carcinogenesis, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM tneilan@partners.org OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-71987, HL-70896] NR 38 TC 65 Z9 67 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 31 PY 2007 VL 116 IS 5 BP 506 EP 514 DI 10.1161/CIRCULATIONAHA.106.652339 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 196BG UT WOS:000248456000008 PM 17638931 ER PT J AU Yea, Y Adil, M Bellas, E Astashkina, A Chaudhary, N Kohane, DS AF Yea, Yoon Adil, Maroof Bellas, Evangelia Astashkina, Anna Chaudhary, Nilika Kohane, Daniel S. TI Prevention of peritoneal adhesions with an in situ cross-linkable hyaluronan hydrogel delivering budesonide SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE peritoneal adhesion; hyaluronan hydrogel; budesonide; drug delivery; repeated injury ID TISSUE PLASMINOGEN-ACTIVATOR; POSTSURGICAL ADHESIONS; DRUG-DELIVERY; RABBIT MODEL; ABDOMINAL ADHESIONS; ACID; SURGERY; RAT; DEXAMETHASONE; MULTICENTER AB Peritoneal adhesions are tissue connections that form within the abdominopelvic cavity following surgery or other injuries. They can cause major medical complications. Barrier devices and pharmacological agents have been used to prevent adhesion formation, with mixed success. We hypothesize that an adhesion barrier which also delivers anti-adhesion drugs can address both physical and physiological causes for adhesion formation. Here, we describe an in situ cross-linking hyaluronan hydrogel (barrier device) containing the glucocorticoid receptor agonist budesonide. Budesonide was chosen because of the known role of inflammation in adhesion formation, hyaluronan because of its known biocompatibility in the peritoneum. The system, consisting of two cross-linkable precursor liquids, was applied using a double-barreled syringe, fort-ning a flexible and durable hydrogel in less than 5 s. We applied this formulation or controls to the injured sites after the second injury in a severe repeat sidewall defect-cecum abrasion model of peritoneal adhesion formation in the rabbit. Large adhesions (median area 15.4 cm(2)) developed in all saline-treated animals. Adhesion formation and area were slightly mitigated in animals treated with budesonide in saline (median area 5.0 cm(2)) or the hydrogel without budesonide (median area 4.9 cm(2)). The incidence and area of adhesions were dramatically reduced in animals treated with budesonide in the hydrogel (median area 0.0 cm(2)). In subcutaneous injections in rats, budesonide in hydrogel reduced inflammation compared to hydrogel alone. In summary, budesonide in a hyaluronan hydrogel is easy to use and highly effective in preventing adhesions in our severe repeated injury model. It is a potentially promising system for post-surgical adhesion prevention, and suggests that the effectiveness of barrier devices can be greatly enhanced by concurrent drug delivery. (c) 2007 Elsevier B.V. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Pediat Intens Care, Lab Biomat & Drug Delivery, Boston, MA 02114 USA. RP Kohane, DS (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dkohane@partners.org RI Adil, Maroof/E-6881-2017 NR 40 TC 6 Z9 6 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JUL 31 PY 2007 VL 120 IS 3 BP 178 EP 185 DI 10.1016/j.jconrel.2007.04.016 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 201YI UT WOS:000248868100005 ER PT J AU Pertin, M Allchorne, AJ Beggah, AT Woolf, CJ Decosterd, I AF Pertin, Marie Allchorne, Andrew J. Beggah, Ahmed T. Woolf, Clifford J. Decosterd, Isabelle TI Delayed sympathetic dependence in the spared nerve injury (SNI) model of neuropathic pain SO MOLECULAR PAIN LA English DT Article ID DORSAL-ROOT GANGLIA; PERIPHERAL-NERVE; RAT MODEL; MECHANICAL ALLODYNIA; LUMBAR SYMPATHECTOMY; GROWTH-FACTOR; ANIMAL-MODEL; INNERVATION; BEHAVIOR; NEURONS AB Background: Clinical and experimental studies of neuropathic pain support the hypothesis that a functional coupling between postganglionic sympathetic efferent and sensory afferent fibers contributes to the pain. We investigated whether neuropathic pain-related behavior in the spared nerve injury (SNI) rat model is dependent on the sympathetic nervous system. Results: Permanent chemical sympathectomy was achieved by daily injection of guanethidine (50 mg/kg s. c.) from age P8 to P21. SNI was performed at adulthood followed by 11 weeks of mechanical and thermal hypersensitivity testing. A significant but limited effect of the sympathectomy on SNI-induced pain sensitivity was observed. The effect was delayed and restricted to cold allodynia-like behavior: SNI-related cold scores were lower in the sympathectomized group compared to the control group at 8 and 11 weeks after the nerve injury but not before. Mechanical hypersensitivity tests (pinprick and von Frey hair threshold tests) showed no difference between groups during the study period. Concomitantly, pericellular tyrosine-hydroxylase immunoreactive basket structures were observed around dorsal root ganglia (DRG) neurons 8 weeks after SNI, but were absent at earlier time points after SNI and in sham operated controls. Conclusion: These results suggest that the early establishment of neuropathic pain-related behavior after distal nerve injury such as in the SNI model is mechanistically independent of the sympathetic system, whereas the system contributes to the maintenance, albeit after a delay of many weeks, of response to cold-related stimuli. C1 Univ Lausanne, CHU Vaudois, Univ Hosp Ctr, Dept Anesthesiol, CH-1011 Lausanne, Switzerland. Univ Lausanne, CHU Vaudois, Univ Hosp Ctr, Anesthesiol Pain Res Unit, CH-1011 Lausanne, Switzerland. Univ Lausanne, Fac Biol & Med, Dept Cell Biol & Morphol, CH-1005 Lausanne, Switzerland. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02921 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Edinburgh, Sch Vet Studies, Neurosci Res Ctr, Div Vet Biomed Sci Royal, Edinburgh EH9 1QH, Midlothian, Scotland. RP Beggah, AT (reprint author), Univ Lausanne, CHU Vaudois, Univ Hosp Ctr, Dept Anesthesiol, CH-1011 Lausanne, Switzerland. EM marie.pertin@unil.ch; andrew.allchorne@ed.ac.uk; ahmed.beggah@unil.ch; cwoolf@partners.org; isabelle.decosterd@unil.ch NR 41 TC 22 Z9 28 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD JUL 31 PY 2007 VL 3 AR 21 DI 10.1186/1744-8069-3-21 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 204FC UT WOS:000249028100001 PM 17672895 ER PT J AU Rodgers, JT Puigserver, P AF Rodgers, Joseph T. Puigserver, Pere TI Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fasting response; glucose metabolism; lipid metabolism; deacetylase; transcriptional coactivator ID PANCREATIC BETA-CELLS; FATTY-ACID OXIDATION; CARDIOVASCULAR-DISEASE; CALORIE RESTRICTION; INSULIN-RESISTANCE; NUCLEAR RECEPTORS; INCREASED DOSAGE; PPAR-GAMMA; LIVER; PGC-1-ALPHA AB In the fasted state, induction of hepatic glucose output and fatty acid oxidation is essential to sustain energetic balance. Production and oxidation of glucose and fatty acids by the liver are controlled through a complex network of transcriptional regulators. Among them, the transcriptional coactivator PGC-1 alpha plays an important role in hepatic and systemic glucose and lipid metabolism. We have previously demonstrated that sirtuin 1 (SIRT1) regulates genes involved in gluconeogenesis through interaction and deacetylation of PGC-1 alpha. Here, we show in vivo that hepatic SIRT1 is a factor in systemic and hepatic glucose, lipid, and cholesterol homeostasis. Knockdown of SIRT1 in liver caused mild hypoglycemia, increased systemic glucose and insulin sensitivity, and decreased glucose production. SIRT1 knockdown also decreased serum cholesterol and increased hepatic free fatty acid and cholesterol content. These metabolic phenotypes caused by SIRT1 knockdown tightly correlated with decreased expression of gluconeogenic, fatty acid oxidation and cholesterol degradation as well as efflux genes. Additionally, overexpression of SIRT1 reversed many of the changes caused by SIRT1 knockdown and depended on the presence of PGC-1 alpha. Interestingly, most of the effects of SIRT1 were only apparent in the fasted state. Our results indicate that hepatic SIRT1 is an important factor in the regulation of glucose and lipid metabolism in response to nutrient deprivation. As these pathways are dysregulated in metabolic diseases, SIRT1 may be a potential therapeutic target to control hyperglycemia and hypercholesterolemia. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jimmy Fund Way 1, Boston, MA 02115 USA. EM pere-puigserver@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK 069966, R01 DK069966] NR 43 TC 283 Z9 298 U1 4 U2 12 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 JUL 31 PY 2007 VL 104 IS 31 BP 12861 EP 12866 DI 10.1073/pnas.0702509104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198CF UT WOS:000248603900049 PM 17646659 ER PT J AU Samii, A Kelly, VE Slimp, JC Shumway-Cook, A Goodkin, R AF Samii, Ali Kelly, Valerie E. Slimp, Jefferson C. Shumway-Cook, Anne Goodkin, Robert TI Staged unilateral versus bilateral subthalamic nucleus stimulator implantation in Parkinson disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson disease; deep brain stimulation; staged surgery; subthalamic nucleus; dyskinesia ID DEEP-BRAIN-STIMULATION; RATING-SCALE AB In 17 consecutive patients with Parkinson disease (PD), bilateral subthalamic nucleus (STN) stimulators were implanted during staged surgeries. The Unified Parkinson Disease Rating Scale (UPDRS) and the Dyskinesia Disability Scale were completed both off and on medication prior to any surgery and also OFF and ON stimulation after each surgery. On-medication UPDRS activities of daily living (ADL) and motor examination scores changed little with unilateral or bilateral stimulation. Off-medication UPDRS motor examination scores improved to similar degrees after each staged STN electrode implantation. Most of the improvements in off-medication ADL scores, dyskinesia scores, complications of therapy, and medication dose reduction occurred after unilateral STN stimulation with smaller improvements after the second operation. (c) 2007 Movement Disorder Society. C1 Univ Washington, Dept Neurol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Neurol Sect, Parkinson Dis Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. RP Samii, A (reprint author), Univ Washington, Dept Neurol, Mail Stop 127,1660 S Columbian Way, Seattle, WA 98108 USA. EM asamii@u.washington.edu OI Kelly, Valerie E./0000-0002-0099-9219 NR 13 TC 20 Z9 21 U1 0 U2 1 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 JUL 30 PY 2007 VL 22 IS 10 BP 1476 EP 1481 DI 10.1002/mds.21554 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 197BJ UT WOS:000248527800016 PM 17523194 ER PT J AU Conklin, SM Harris, JI Manuck, SB Yao, JK Hibbeln, JR Muldoon, MF AF Conklin, Sarah M. Harris, Jennifer I. Manuck, Stephen B. Yao, Jeffrey K. Hibbeln, Joseph R. Muldoon, Matthew F. TI Serum omega-3 fatty acids are associated with variation in mood, personality and behavior in hypercholesterolemic community volunteers SO PSYCHIATRY RESEARCH LA English DT Article DE polyunsaturated fatty acids (PUFA); depression; impulsivity; personality ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; PRELIMINARY DOUBLE-BLIND; BLOOD-CELL MEMBRANES; DOCOSAHEXAENOIC ACID; FISH CONSUMPTION; MAJOR DEPRESSION; CARDIOVASCULAR-DISEASE AB Low dietary intake of omega-3 polyunsaturated fatty acids has been linked to several features of psychiatric symptomatology, including depression, disorders of impulse control, and hostility. Preliminary intervention trials of omega-3 fatty acid supplementation for clinical depression and other disorders have reported benefit. However, few studies have investigated the relationships between these fatty acids and normative variability in mood, behavior and personality. Participants were 105 hypercholesterolemic, but otherwise healthy, non-smoking adults. Fasting serum alpha-linolenic (alpha-LNA), eicosapentaenoic (EPA) and docosahexacnoic acid (DHA) were assayed with gas chromatography. Participants completed the Beck Depression Inventory (BDI), the NEO Five Factor Personality Inventory (NEO-FFI) and the Barratt Impulsiveness Scale (BIS). In multivariate analyses, higher levels of the long chain omega-3 PUFAs, EPA and DHA, were associated with significantly reduced odds of scoring >= 10 on the BDI. Similarly, DHA and EPA covaried inversely with NEO-Neuroticism scores, whereas DHA was positively associated with NEO-Agreeableness. On the BIS, DHA was inversely related to cognitive impulsivity and alpha-LNA was inversely related to motor and total impulsivity. These findings suggest that omega-3 fatty acid status is associated with variability in affect regulation, personality and impulse control. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Cardiovasc Behav Med Postdoctoral Training Progra, Pittsburgh, PA USA. Brown Univ, Dept Psychol, Providence, RI 02912 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat & Pharmaceut Sci, VA Pittsburgh Healthcare syst, Pittsburgh, PA USA. Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Conklin, SM (reprint author), Univ Pittsburgh, Dept Psychiat, 506 Old Engn Hall, Pittsburgh, PA 15260 USA. EM conklinsm@upmc.edu FU NHLBI NIH HHS [HL46328, HL07560] NR 72 TC 43 Z9 45 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 30 PY 2007 VL 152 IS 1 BP 1 EP 10 DI 10.1016/j.psychres.2006.10.006 PG 10 WC Psychiatry SC Psychiatry GA 198UO UT WOS:000248653200001 PM 17383013 ER PT J AU Zhang, H Li, JA Barrington, RA Liang, G Qin, GJ Liu, DX AF Zhang, Haimou Li, Jinan Barrington, Robert A. Liang, Gang Qin, Gangjian Liu, Dong-Xu TI An anti-endotoxin peptide that generates from the amino-terminal domain of complement regulatory protein C1 inhibitor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE complement; inflammation; peptide ID TUMOR-NECROSIS-FACTOR; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; PERMEABILITY-INCREASING PROTEIN; N-LINKED GLYCOSYLATION; LIPID-A; ENDOTOXIN-SHOCK; INACTIVATION; ELASTASE; MICE; MECHANISM AB C1 inhibitor (C1INH), a complement regulatory protein, prevents endotoxin shock via a direct interaction of the amino-terminal domain with gram-negative bacterial lipopolysaccharide (LPS). Importantly, the cleaved, inactive C1INH still is an anti-endotoxin effector indicating the anti-endotoxin peptide that generates from the amino-terminal domain of C1INK In this study, we first identified that a cleaved fragment within the major part of the amino-terminal domain in in vitro proteolytic analysis of C1INH had an ability to bind to LPS. We synthesized several peptides overlapping the C1INH cleaved fragment. Among these synthetic peptides, a 13-mer derivative peptide at position from 18 to 30, named N2((18-30)), exhibited the most powerful anti-endotoxin activity in vitro, enlightening that it was most strong at binding to LPS, inhibiting the interaction of LPS with LPS-binding protein (LBP), blocking LPS binding to CID 14(+) cells, and suppressing production of tumor necrosis factor (TNF)-alpha by murine macrophages, RAW 264.7. In the murine endotoxin shock model, the peptide N2((18-30)) protected mice from LPS-induced lethal septic shock by inhibiting macrophage activation. These data indicate that the peptide N2((18-30)) derived from the amino-terminal region of C1INH is anti-endotoxin. (c) 2007 Elsevier Inc. All rights reserved. C1 Hubei Univ, Sch Life Sci, Ctr Infect & Immun Res, Wuhan, Hubei, Peoples R China. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL USA. RP Liu, DX (reprint author), Hubei Univ, Sch Life Sci, Ctr Infect & Immun Res, 11 Xue Yuan Rd, Wuhan, Hubei, Peoples R China. EM dxliu001@yahoo.com NR 28 TC 5 Z9 5 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 27 PY 2007 VL 359 IS 2 BP 285 EP 291 DI 10.1016/j.bbrc.2007.05.078 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 182GZ UT WOS:000247494400016 PM 17543887 ER PT J AU Hsieh, GR Schnickel, GT Garcia, C Shefizadeh, A Fishbein, MC Ardehali, A AF Hsieh, George R. Schnickel, Gabriel T. Garcia, Consuelo Shefizadeh, Ali Fishbein, Michael C. Ardehali, Abbas TI Inflammation/oxidation in chronic rejection: Apolipoprotein A-I mimetic peptide reduces chronic rejection of transplanted hearts SO TRANSPLANTATION LA English DT Article DE T-lymphocyte; hemoxygenase-1; apolipoprotein; rejection ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE CHEMOTACTIC PROTEIN-1; HEME OXYGENASE-1; CARBON-MONOXIDE; ALLOGRAFT-REJECTION; T-LYMPHOCYTES; MICE; D-4F; INJURY; CHOLESTEROL AB Background. Chronic rejection in transplanted hearts or cardiac allograft vasculopathy (CAV) is the leading cause of late death among heart transplant recipients. Strategies to control CAV traditionally have focused on lymphocyte functions. We hypothesized that D-4F, an apoA-I mimetic peptide with potent anti-inflammatory/antioxidant properties, will attenuate CAV. Methods. We used a previously characterized murine model of CAV.B6.C-H2(bm12) hearts were heterotopically transplanted into C57BL/6 mice. Recipient mice were treated with either 20 mu g of D-4F or carrier daily. Donor hearts were harvested on day 24 after transplantation. Results. Treatment of recipients with D-4F reduced the severity of intimal. lesions (62.5 +/- 3.4% vs. 31.1 +/- 8.7%, P<0.009). Treatment also resulted in a decrease in the number of graft-infiltrating CD4 and CD8 lymphocytes and CXCR3+ T-lymphocyte subsets. Heme oxygenase-1 (HO-1) gene transcript in the donor hearts was up-regulated with D-4F treatment, and HO-1 blockade partially reversed the beneficial effects of D-4F. In vitro studies showed that D-4F reduced allogeneic T-lymphocyte proliferation and effector cytokine production. These processes were HO-1 independent. Conclusion. This study suggests that D-4F, a prototypical apoA-I mimetic peptide, is effective in controlling CAV via induction of HO-1 in the graft and a direct effect on T-lymphocyte function. This class of peptides with anti-inflammatory/antioxidant properties provides a novel strategy in the treatment of CAV. C1 Univ Calif Los Angeles, Med Ctr, Div Cardiac Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Gaffen Sch Med, Dept Surg, Div Cardiac Surg, Los Angeles, CA USA. W Los Angles VA Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Gaffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. RP Ardehali, A (reprint author), Univ Calif Los Angeles, Med Ctr, Div Cardiac Surg, 62-182 CHS,10833 Conte Ave, Los Angeles, CA 90095 USA. EM aardehali@mednet.ucla.edu OI Schnickel, Gabriel/0000-0003-4392-2200 NR 36 TC 19 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 2007 VL 84 IS 2 BP 238 EP 243 DI 10.1097/01.tp.0000268509.60200.ea PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 194ZG UT WOS:000248381700015 PM 17667816 ER PT J AU Mishra, BK Wu, T Belfer, I Hodgkinson, CA Cohen, LG Kiselycznyk, C Kingman, A Keller, RB Yuan, Q Goldman, D Atlas, SJ Max, MB AF Mishra, Bikash K. Wu, Tianxia Belfer, Inna Hodgkinson, Colin A. Cohen, Leonardo G. Kiselycznyk, Carly Kingman, Albert Keller, Robert B. Yuan, Qiaoping Goldman, David Atlas, Steven J. Max, Mitchell B. TI Do motor control genes contribute to interindividual variability in decreased movement in patients with pain? SO MOLECULAR PAIN LA English DT Article ID LOW-BACK-PAIN; CHRONIC MUSCULOSKELETAL PAIN; BED REST; RECEPTOR GENE; ADRENERGIC-RECEPTOR; FEAR-AVOIDANCE; LUMBAR SPINE; POLYMORPHISM; ASSOCIATION; MODEL AB Background: Because excessive reduction in activities after back injury may impair recovery, it is important to understand and address the factors contributing to the variability in motor responses to pain. The current dominant theory is the "fear-avoidance model", in which the some patients' heightened fears of further injury cause them to avoid movement. We propose that in addition to psychological factors, neurochemical variants in the circuits controlling movement and their modification by pain may contribute to this variability. A systematic search of the motor research literature and genetic databases yielded a prioritized list of polymorphic motor control candidate genes. We demonstrate an analytic method that we applied to 14 of these genes in 290 patients with acute sciatica, whose reduction in movement was estimated by items from the Roland-Morris Disability Questionnaire. Results: We genotyped a total of 121 single nucleotide polymorphisms (SNPs) in 14 of these genes, which code for the dopamine D2 receptor, GTP cyclohydrolase I, glycine receptor alpha 1 subunit, GABA-A receptor alpha 2 subunit, GABA-A receptor beta 1 subunit, alpha-adrenergic 1C, 2A, and 2C receptors, serotonin 1A and 2A receptors, cannabinoid CB-1 receptor, M1 muscarinic receptor, and the tyrosine hydroxylase, and tachykinin precursor-1 molecules. No SNP showed a significant association with the movement score after a Bonferroni correction for the 14 genes tested. Haplotype analysis of one of the blocks in the GABA-A receptor beta 1 subunit showed that a haplotype of 11% frequency was associated with less limitation of movement at a nominal significance level value (p = 0.0025) almost strong enough to correct for testing 22 haplotype blocks. Conclusion: If confirmed, the current results may suggest that a common haplotype in the GABA-A beta 1 subunit acts like an "endogenous muscle relaxant" in an individual with subacute sciatica. Similar methods might be applied a larger set of genes in animal models and human laboratory and clinical studies to understand the causes and prevention of pain-related reduction in movement. C1 Natl Inst Dent & Craniofacial Res, Clin Pain Res Sect, Lab Sensory Biol, NIH,DHHS, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, NIH, DHHS, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Div Populat & Hlth Promot Sci, NIH, DHHS, Bethesda, MD USA. NINDS, Human Cort Physiol Sect, NIH, DHHS, Rockville, MD USA. Maine Spine & Rehabil, Portland, ME USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Gen Med Div, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Clin Epidemiol Unit, Boston, MA USA. RP Max, MB (reprint author), Natl Inst Dent & Craniofacial Res, Clin Pain Res Sect, Lab Sensory Biol, NIH,DHHS, Bethesda, MD 20892 USA. EM mbikashkumar@hotmail.com; wuti@mail.nih.gov; ibelfer@mail.nih.gov; chodg@mail.nih.gov; cohenl@ninds.nih.gov; kiselycznykc@mail.nih.gov; kingmana@mail.nih.gov; rbkeller@wildblue.net; qyuan@mail.nih.gov; dgneuro@mail.nih.gov; satlas@partners.org; mm77k@nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU AHRQ HHS [HS-06344, HS-08194, HS-09804, R01 HS009804]; Intramural NIH HHS [Z99 AA999999]; NIAAA NIH HHS [Z01 AA000303]; NIDCR NIH HHS [Z01 DE000366] NR 55 TC 7 Z9 7 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD JUL 26 PY 2007 VL 3 AR 20 DI 10.1186/1744-8069-3-20 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 229UA UT WOS:000250829700001 PM 17655760 ER PT J AU Xavier, RJ Podolsky, DK AF Xavier, R. J. Podolsky, D. K. TI Unravelling the pathogenesis of inflammatory bowel disease SO NATURE LA English DT Review ID GENOME-WIDE ASSOCIATION; INTESTINAL EPITHELIAL-CELLS; REGULATORY T-CELLS; PLACEBO-CONTROLLED TRIAL; CROHNS-DISEASE; ULCERATIVE-COLITIS; DENDRITIC CELLS; IMMUNE-SYSTEM; OLIGOMERIZATION DOMAIN-2; SIGNALING PATHWAYS AB Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria ( or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/ mucosal immunopathology of IBD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM dpodolsky@partners.org NR 98 TC 1792 Z9 1867 U1 52 U2 354 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUL 26 PY 2007 VL 448 IS 7152 BP 427 EP 434 DI 10.1038/nature06005 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193VG UT WOS:000248302700038 PM 17653185 ER PT J AU Tsai, TT Evangelista, A Nienaber, CA Myrmel, T Meinhardt, G Cooper, JV Smith, DE Suzuki, T Fattori, R Llovet, A Froehlich, J Hutchison, S Distante, A Sundt, T Beckman, J Januzzi, JL Isselbacher, EM Eagle, KA AF Tsai, Thomas T. Evangelista, Arturo Nienaber, Christoph A. Myrmel, Truls Meinhardt, Gabriel Cooper, Jeanna V. Smith, Dean E. Suzuki, Toru Fattori, Rossella Llovet, Alfredo Froehlich, James Hutchison, Stuart Distante, Alessandro Sundt, Thoralf Beckman, Joshua Januzzi, James L., Jr. Isselbacher, Eric M. Eagle, Kim A. CA Int Registry Acute Aortic Dissecti TI Partial thrombosis of the false lumen in patients with acute type B aortic dissection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STENT-GRAFT PLACEMENT; INTRALUMINAL THROMBUS; FOLLOW-UP; MANAGEMENT; ANEURYSM; ECHOCARDIOGRAPHY; PROGNOSIS; DIAGNOSIS; THERAPY; ELASTIN AB Background: Patency or thrombosis of the false lumen in type B acute aortic dissection has been found to predict outcomes. The prognostic implications of partial thrombosis of the false lumen have not yet been elucidated. Methods: We examined 201 patients with type B acute aortic dissection who were enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2003 and who survived to hospital discharge. Kaplan-Meier mortality curves were stratified according to the status of the false lumen (patent, partial thrombosis, or complete thrombosis) as determined during the index hospitalization. Cox proportional-hazards analysis was performed to identify independent predictors of death. Results: During the index hospitalization, 114 patients (56.7%) had a patent false lumen, 68 patients (33.8%) had partial thrombosis of the false lumen, and 19 (9.5%) had complete thrombosis of the false lumen. The mean (+/-SD) 3-year mortality rate for patients with a patent false lumen was 13.7+/-7.1%, for those with partial thrombosis was 31.6+/-12.4%, and for those with complete thrombosis was 22.6+/-22.6% (median follow-up, 2.8 years; P=0.003 by the log-rank test). Independent predictors of postdischarge mortality were partial thrombosis of the false lumen (relative risk, 2.69; 95% confidence interval [CI], 1.45 to 4.98; P=0.002), a history of aortic aneurysm (relative risk, 2.05; 95% CI, 1.07 to 3.93; P=0.03), and a history of atherosclerosis (relative risk, 1.87; 95% CI, 1.01 to 3.47; P=0.05). Conclusions: Mortality is high after discharge from the hospital among patients with type B acute aortic dissection. Partial thrombosis of the false lumen, as compared with complete patency, is a significant independent predictor of postdischarge mortality in these patients. C1 Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. Hosp Gen Univ Vall dHebron, Barcelona, Spain. Univ Rostock, Rostock, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Tokyo, Tokyo, Japan. Univ Hosp S Orsola, Bologna, Italy. Hosp Univ 12 Octubre, Madrid, Spain. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. CNR, Lecce, Italy. Mayo Clin, Rochester, MN USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tsai, TT (reprint author), Univ Michigan, Ctr Cardiovasc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM hsianshi@umich.edu OI Beckman, Joshua/0000-0001-8332-8439 FU NHLBI NIH HHS [5T32HL007853-08] NR 37 TC 250 Z9 266 U1 0 U2 4 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 JUL 26 PY 2007 VL 357 IS 4 BP 349 EP 359 DI 10.1056/NEJMoa063232 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 193OL UT WOS:000248283500006 PM 17652650 ER PT J AU Duggan, CP Westra, SJ Rosenberg, AE Grinspan, ZM Harris, NL Whelan, JP Seashore, C Rosenberg, AE AF Duggan, Christopher P. Westra, Sjirk J. Rosenberg, Andrew E. Grinspan, Zachary M. Harris, Nancy Lee Whelan, J. Patrick Seashore, Carl Rosenberg, Andrew E. TI A boy with bone pain, rash, and gingival hypertrophy - Scurvy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RECURRENT MULTIFOCAL OSTEOMYELITIS; PERVASIVE DEVELOPMENTAL DISORDER; VITAMIN-A; CHILDREN; AUTISM; POPULATION; SECRETIN C1 Childrens Hosp, Dept Med, Div Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 Pathol, Boston, MA 02115 USA. RP Duggan, CP (reprint author), Childrens Hosp, Dept Med, Div Gastroenterol & Nutr, Boston, MA 02115 USA. NR 19 TC 29 Z9 29 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 26 PY 2007 VL 357 IS 4 BP 392 EP 400 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 193OL UT WOS:000248283500013 PM 17652655 ER PT J AU Hirai, M Horiguchi, M Ohbayashi, T Kita, T Chien, KR Nakamura, T AF Hirai, Maretoshi Horiguchi, Masahito Ohbayashi, Tetsuya Kita, Toru Chien, Kenneth R. Nakamura, Tomoyuki TI Latent TGF-beta-binding protein 2 binds to DANCE/fibulin-5 and regulates elastic fiber assembly SO EMBO JOURNAL LA English DT Article DE DANCE; elastic fiber; fibulin-5; LTBP-2; microfibril ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; DEVELOPMENTAL EXPRESSION; MOLECULAR-CLONING; IN-VIVO; MICROFIBRILS; FIBRILLIN-1; IDENTIFICATION; COMPONENT; FIBULIN-5 AB Elastic fibers play the principal roles in providing elasticity and integrity to various types of human organs, such as the arteries, lung, and skin. However, the molecular mechanism of elastic fiber assembly that leads to deposition and crosslinking of elastin along microfibrils remains largely unknown. We have previously shown that developing arteries and neural crest EGF-like protein (DANCE) ( also designated fibulin-5) is essential for elastogenesis by studying DANCE-deficient mice. Here, we report the identification of latent transforming growth factor-beta-binding protein 2 (LTBP-2), an elastic fiber-associating protein whose function in elastogenesis is not clear, as a DANCE-binding protein. Elastogenesis assays using human skin fibroblasts reveal that fibrillar deposition of DANCE and elastin is largely dependent on fibrillin-1 microfibrils. However, downregulation of LTBP-2 induces fibrillin-1-independent fibrillar deposition of DANCE and elastin. Moreover, recombinant LTBP-2 promotes deposition of DANCE onto fibrillin-1 microfibrils. These results suggest a novel regulatory mechanism of elastic fiber assembly in which LTBP-2 regulates targeting of DANCE on suitable microfibrils to form elastic fibers. C1 Kansai Med Univ, Dept Pharmacol, Moriguchi, Osaka 5708506, Japan. Kyoto Univ, Horizontal Med Res Org, Grad Sch Med, Kyoto, Japan. Kyoto Univ, Dept Cardiovasc Med, Grad Sch Med, Kyoto, Japan. Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. RP Nakamura, T (reprint author), Kansai Med Univ, Dept Pharmacol, 10-15 Fumizono Cho, Moriguchi, Osaka 5708506, Japan. EM nakamtom@takii.kmu.ac.jp NR 38 TC 69 Z9 72 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 25 PY 2007 VL 26 IS 14 BP 3283 EP 3295 DI 10.1038/sj.emboj.7601768 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199DE UT WOS:000248675600002 PM 17581631 ER PT J AU Brown, L Ongusaha, PP Kim, HG Nuti, S Mandinova, A Lee, JW Khosravi-Far, R Aaronson, SA Lee, SW AF Brown, Lauren Ongusaha, Pat P. Kim, Hyung-Gu Nuti, Shanthy Mandinova, Anna Lee, Ji Won Khosravi-Far, Roya Aaronson, Stuart A. Lee, Sam W. TI CDIP, a novel pro-apoptotic gene, regulates TNF alpha-mediated apoptosis in a p53-dependent manner SO EMBO JOURNAL LA English DT Article DE apoptosis; CDIP; p53; TNF-alpha ID TUMOR-NECROSIS-FACTOR; APO-1/FAS RECEPTOR/LIGAND SYSTEM; DRUG-INDUCED APOPTOSIS; WILD-TYPE P53; BINDING-SITE; SIGNAL-TRANSDUCTION; IONIZING-RADIATION; DNA-DAMAGE; DEATH; KILLER/DR5 AB We have identified a novel pro-apoptotic p53 target gene named CDIP ( Cell Death Involved p53-target). Inhibition of CDIP abrogates p53-mediated apoptotic responses, demonstrating that CDIP is an important p53 apoptotic effector. CDIP itself potently induces apoptosis that is associated with caspase-8 cleavage, implicating the extrinsic cell death pathway in apoptosis mediated by CDIP. siRNA-directed knockdown of caspase-8 results in a severe impairment of CDIP-dependent cell death. In investigating the potential involvement of extrinsic cell death pathway in CDIP-mediated apoptosis, we found that TNF-alpha expression tightly correlates with CDIP expression, and that inhibition of TNF-alpha signaling attenuates CDIP-dependent apoptosis. We also demonstrate that TNF-alpha is upregulated in response to p53 and p53 inducing genotoxic stress, in a CDIP-dependent manner. Consistently, knockdown of TNF-alpha impairs p53-mediated stress-induced apoptosis. Together, these findings support a novel p53 -> CDIP -> TNF-alpha apoptotic pathway that directs apoptosis after exposure of cells to genotoxic stress. Thus, CDIP provides a new link between p53-mediated intrinsic and death receptor-mediated extrinsic apoptotic signaling, providing a novel target for cancer therapeutics aimed at maximizing the p53 apoptotic response of cancer cells to drug therapy. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu FU NCI NIH HHS [R01 CA071672, CA078356, CA097216, CA80058, CA85681, P01 CA080058, R01 CA078356, R01 CA085681, R01 CA097216, R01 CA142805, R01 CA149477] NR 34 TC 21 Z9 24 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 25 PY 2007 VL 26 IS 14 BP 3410 EP 3422 DI 10.1038/sj.emboj.7601779 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199DE UT WOS:000248675600012 PM 17599062 ER PT J AU Seijffers, R Mills, CD Woolf, CJ AF Seijffers, Rhona Mills, Charles D. Woolf, Clifford J. TI ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ATF3; DRG; axon; nerve regeneration; myelin inhibition; growth-associated genes ID DORSAL-ROOT GANGLION; MYELIN-ASSOCIATED GLYCOPROTEIN; CHONDROITIN SULFATE PROTEOGLYCANS; PROMOTES NEURITE OUTGROWTH; PRIMARY SENSORY NEURONS; RECEPTOR FAMILY-MEMBER; AXONAL REGENERATION; C-JUN; TRANSCRIPTION FACTOR; CONDITIONING LESION AB Peripheral axons of dorsal root ganglion (DRG) neurons, but not their central axons in the dorsal columns, regenerate after injury. However, if the neurons are conditioned by a peripheral nerve injury into an actively growing state, the rate of peripheral axonal growth is accelerated and the injured central axons begin to regenerate. The growth-promoting effects of conditioning injuries have two components, increased axonal growth and a reduced response to inhibitory myelin cues. We have examined which transcription factors activated by peripheral axonal injury may mediate the conditioning effect by regulating expression of effectors that increase the intrinsic growth state of the neurons. Activating transcription factor 3 (ATF3) is a prime candidate because it is induced in all injured DRG neurons after peripheral, but not central, axonal damage. To investigate if ATF3 promotes regeneration, we generated transgenic mice that constitutively express this transcription factor in non-injured adult DRG neurons. The rate of peripheral nerve regeneration was enhanced in the transgenic mice to an extent comparable to that produced by a preconditioning nerve injury. The expression of some growth-associated genes, such as SPRR1A, but not others like GAP-43, was increased in the non-injured neurons. ATF3 increased DRG neurite elongation when cultured on permissive substrates but did not overcome the inhibitory effects of myelin or promote central axonal regeneration in the spinal cord in vivo. We conclude that ATF3 contributes to nerve regeneration by increasing the intrinsic growth state of injured neurons. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. EM woolf.clifford@mgh.harvard.edu FU NINDS NIH HHS [NS039518, NS45459] NR 80 TC 170 Z9 173 U1 2 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 25 PY 2007 VL 27 IS 30 BP 7911 EP 7920 DI 10.1523/JNEUROSCI.5313-06.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 196MA UT WOS:000248484800004 PM 17652582 ER PT J AU Lu, L Zheng, L Viera, L Suswam, E Li, YY Li, XL Estevez, AG King, PH AF Lu, Liang Zheng, Lei Viera, Liliana Suswam, Esther Li, Yanyan Li, Xuelin Estevez, Alvaro G. King, Peter H. TI Mutant Cu/Zn-superoxide dismutase associated with amyotrophic lateral sclerosis destabilizes vascular endothelial growth factor mRNA and downregulates its expression SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AU-rich element; 3 '-untranslated region; RNA-binding proteins; posttranscriptional gene regulation; HuR translocation; motor neurons ID TUMOR-NECROSIS-FACTOR; BINDING PROTEIN HUR; AU-RICH ELEMENTS; MOTOR-NEURON DEGENERATION; G93A-SOD1 MOUSE MODEL; T-CELL-ACTIVATION; ANGIOGENIC FACTOR; MOTONEURON DEGENERATION; UNTRANSLATED REGION; PROLONGS SURVIVAL AB Vascular endothelial growth factor (VEGF) plays a neuroprotective role in mice harboring mutations of copper-zinc superoxide dismutase 1 (SOD 1) in familial amyotrophic lateral sclerosis (ALS). Conversely, the loss of VEGF expression through genetic depletion can give rise to a phenotype resembling ALS independent of SOD 1 mutations. Here, we observe a profound downregulation of VEGF mRNA expression in spinal cords of G93A SOD 1 mice that occurred early in the course of the disease. Using an in vitro culture model of glial cells expressing mutant SOD 1, we demonstrate destabilization and downregulation of VEGF RNA with concomitant loss of protein expression that correlates with level of transgene expression. Using a luciferase reporter assay, we show that this molecular effect is mediated through a portion of the VEGF 3'-untranslated region (UTR) that harbors a class II adenylate/uridylate-rich element. Other mutant forms of SOD 1 produced a similar negative effect on luciferase RNA and protein expression. Mobility shift assay with a VEGF 3'-UTR probe reveals an aberrantly migrating complex that contains mutant SOD I. We further show that the RNA stabilizing protein, HuR (human antigen R), is translocated from nucleus to cytoplasm in mutant SOD 1 cells in vitro and mouse motor neurons in vivo. In summary, our data suggest that mutant SOD 1 gains a novel function, possibly by altering the ribonucleoprotein complex with the VEGF 3'-UTR. We postulate that the resultant dysregulation of VEGF posttranscriptional processing critically reduces the level of this neuroprotective growth factor and accelerates the neurodegenerative process in ALS. C1 Univ Alabama, Dept Neurol, Birmingham, AL 35295 USA. Univ Alabama, Dept Genet, Birmingham, AL 35295 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35295 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35295 USA. Cornell Univ, Weill Med Coll, Lab Motor Neuron Biol, Burke Med Res Inst, White Plains, NY 10605 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, White Plains, NY 10605 USA. RP King, PH (reprint author), 1530 3rd Ave S, Birmingham, AL 35294 USA. EM pking@uab.edu FU NCI NIH HHS [CA97247]; NINDS NIH HHS [NS42834, NS36761] NR 73 TC 37 Z9 38 U1 0 U2 1 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 JUL 25 PY 2007 VL 27 IS 30 BP 7929 EP 7938 DI 10.1523/JNEUROSCI.1877-07.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 196MA UT WOS:000248484800006 PM 17652584 ER PT J AU Kelly, KA Carson, J McCarthy, JR Weissleder, R AF Kelly, Kimberly A. Carson, Jonathan McCarthy, Jason R. Weissleder, Ralph TI Novel Peptide Sequence ("IQ-tag'') with High Affinity for NIR Fluorochromes Allows Protein and Cell Specific Labeling for In Vivo Imaging SO PLOS ONE LA English DT Article AB Background. Probes that allow site-specific protein labeling have become critical tools for visualizing biological processes. Methods. Here we used phage display to identify a novel peptide sequence with nanomolar affinity for near infrared (NIR) (benz) indolium fluorochromes. The developed peptide sequence ("IQ-tag'') allows detection of NIR dyes in a wide range of assays including ELISA, flow cytometry, high throughput screens, microscopy, and optical in vivo imaging. Significance. The described method is expected to have broad utility in numerous applications, namely site-specific protein imaging, target identification, cell tracking, and drug development. C1 [Kelly, Kimberly A.; Carson, Jonathan; McCarthy, Jason R.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. EM weissleder@helix.mgh.harvard.edu FU NIH [R24-CA92782, P50-CA86355]; Sandler Foundation FX NIH R24-CA92782 and P50-CA86355, Sandler Foundation (R.W.) NR 19 TC 15 Z9 16 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 25 PY 2007 VL 2 IS 7 AR e665 DI 10.1371/journal.pone.0000665 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10GJ UT WOS:000207452200027 PM 17653285 ER PT J AU Ingelsson, E Sullivan, LM Fox, CS Murabito, JM Benjamin, EJ Polak, JF Meigs, JB Keyes, MJ O'Donnell, CJ Wang, TJ D'Agostino, RB Wolf, PA Vasan, RS AF Ingelsson, Erik Sullivan, Lisa M. Fox, Caroline S. Murabito, Joanne M. Benjamin, Emelia J. Polak, Joseph F. Meigs, James B. Keyes, Michelle J. O'Donnell, Christopher J. Wang, Thomas J. D'Agostino, Ralph B. Wolf, Philip A. Vasan, Ramachandran S. TI Burden and prognostic importance of subclinical cardiovascular disease in overweight and obese individuals SO CIRCULATION LA English DT Article DE atherosclerosis; cardiovascular diseases; epidemiology; obesity; risk factors ID LEFT-VENTRICULAR HYPERTROPHY; CORONARY-HEART-DISEASE; BODY-MASS INDEX; BLOOD-PRESSURE; PLASMA HOMOCYSTEINE; RISK-FACTORS; ATHEROSCLEROSIS; ADULTS; ASSOCIATION; PREVALENCE AB Background - The burden and prognostic importance of subclinical cardiovascular disease (CVD) in obesity has not been investigated systematically. Methods and Results - We examined prevalence of subclinical disease in 1938 Framingham Study participants (mean age, 57 years; 59% women) by use of 5 tests (electrocardiography, echocardiography, carotid ultrasound, ankle-brachial pressure, and urinary albumin excretion) and stratified by body mass index (BMI) ( normal, < 25; overweight, 25 to < 30.0; obese, >= 30 kg/m(2)) and waist circumference (WC) ( increased, >= 88 cm for women or >= 102 cm for men). We investigated risk of overt CVD associated with adiposity according to presence versus absence of subclinical disease on any of the 5 tests. Prevalence of subclinical disease was higher in overweight (40.0%; adjusted odds ratio, 1.68) and obese individuals (49.7%; odds ratio, 2.82) compared with individuals with normal BMI (29.3%) and in individuals with increased WC (44.9%; odds ratio, 1.67) compared with normal WC (31.9%). On follow-up (mean 7.2 years), 139 participants had developed overt CVD. Presence of subclinical disease was associated with > 2-fold risk of overt CVD in all BMI and WC strata, with no evidence of an interaction between BMI and subclinical disease. CVD risk was attenuated in participants with obesity or increased WC but without subclinical disease ( adjusted hazard ratio for obesity, 1.57; 95% confidence interval, 0.74 to 3.33; adjusted hazard ratio for increased WC, 1.22; 95% confidence interval, 0.69 to 2.15), compared with individuals with normal BMI or WC and no subclinical disease, respectively. Conclusions - In our community-based sample, overweight and obesity were associated with high prevalence of subclinical disease, which partly contributed to the increased risk of overt CVD in these strata. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [1R01HL080124, 2K24HL04334, K23-HL074077-01, N01-HC-25195] NR 34 TC 34 Z9 41 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 JUL 24 PY 2007 VL 116 IS 4 BP 375 EP 384 DI 10.1161/CIRCULATIONAHA.107.688788 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 193AA UT WOS:000248244300004 PM 17620505 ER PT J AU Pittet, MJ Grimm, J Berger, CR Tamura, T Wojtkiewicz, G Nahrendorf, M Romero, P Swirski, FK Weissleder, R AF Pittet, Mikael J. Grimm, Jan Berger, Cedric R. Tamura, Takahiko Wojtkiewicz, Gregory Nahrendorf, Matthias Romero, Pedro Swirski, Filip K. Weissleder, Ralph TI In vivo imaging of T cell delivery to tumors after adoptive transfer therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; immunity; CD8 T cell ID STEM-CELLS; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; CANCER REGRESSION; EFFECTOR FUNCTION; IMMUNOTHERAPY; TOLERANCE; MIGRATION; RESPONSES; TRANSPLANTATION AB Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of In-111-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because In-111-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies. C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Univ Hosp, Ludwig Inst Canc Res, Div Clin Oncoimmuol, CH-1011 Lausanne, Switzerland. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu RI Grimm, Jan/B-1937-2008; TAMURA, Takahiko/D-8413-2015 FU NCI NIH HHS [P50 CA086355, R24-CA92782, P50-CA086355, U54-CA126515-01, U54 CA126515, R24 CA092782] NR 47 TC 53 Z9 54 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 24 PY 2007 VL 104 IS 30 BP 12457 EP 12461 DI 10.1073/pnas.0704460104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 196HK UT WOS:000248472100041 PM 17640914 ER PT J AU Dublin, S Lumley, T Glazer, NL Psaty, BM French, B Wiggins, KL Smith, NL Heckbert, SR AF Dublin, Sascha Lumley, Thomas Glazer, Nicole L. Psaty, Bruce M. French, Benjamin Wiggins, Kerri L. Smith, Nicholas L. Heckbert, Susan R. TI Atrial fibrillation, obesity, and obstructive sleep apnea - Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. RP Dublin, S (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Metropolitan Pk W,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Sascha.Dublin@va.gov NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 23 PY 2007 VL 167 IS 14 BP 1553 EP 1553 DI 10.1001/archinte.167.14.1553-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 192UY UT WOS:000248230100020 ER PT J AU Pieters, R Schrappe, M De Lorenzo, P Hann, I De Rossi, G Felice, M Hovi, L LeBlanc, T Szczepanski, T Ferster, A Janka, G Rubnitz, J Silverman, L Stary, J Campbell, M Li, CK Mann, G Suppiah, R Biondi, A Vora, A Valsecchi, MG AF Pieters, Rob Schrappe, Martin De Lorenzo, Paola Hann, Ian De Rossi, Giulio Felice, Maria Hovi, Liisa LeBlanc, Thierry Szczepanski, Tomasz Ferster, Alice Janka, Gritta Rubnitz, Jeffrey Silverman, Lewis Stary, Jan Campbell, Myriam Li, Chi-Kong Mann, Georg Suppiah, Ram Biondi, Andrea Vora, Ajay Valsecchi, Maria Grazia TI A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial SO LANCET LA English DT Article ID CHILDRENS CANCER GROUP; MLL GENE; ONCOLOGY-GROUP; CYTOSINE-ARABINOSIDE; CELL TRANSPLANTATION; PROGNOSTIC-FACTORS; CLINICAL-TRIALS; CHEMOTHERAPY; THERAPY; REARRANGEMENTS AB Background Acute lymphoblastic leukaemia in infants younger than 1 year is rare, and infants with the disease have worse outcomes than do older children. We initiated an international study to investigate the effects of a new hybrid treatment protocol with elements designed to treat both acute lymphoblastic: leukaemia and acute myeloid leukaemia, and to identify any prognostic factors for outcome in infants. We also did a randomised trial to establish the value of a late intensification course. Methods Patients aged 0-12 months were enrolled by 17 study groups in 22 countries between 1999 and 2005. Eligible patients were stratified for risk according to their peripheral blood response to a 7-day prednisone prophase, and then given a hybrid regimen based on the standard protocol for acute lymphoblastic leukaemia, with some elements designed for treatment of acute myeloid leukaemia. Before the maintenance phase, a subset of patients in complete remission were randomly assigned to receive either standard treatment or a more intensive chemotherapy course with high-dose cytarabine and methotrexate. The primary outcomes were event-free survival (EFS) for the initial cohort of patients and disease-free survival (DFS) for the patients randomly assigned to a treatment group. Data were analysed on an intention-to-treat basis. This trial was registered with ClinicalTrials.gov, number NCT 00015873, and at controlled-trials.com, number ISRCTN24251487. Findings In the 482 enrolled patients who underwent hybrid treatment, 260 (58%) were in complete remission at a median follow-up of 38 (range 1-78) months, and EFS at 4 years was 47.0% (SE 2.6, 95% CI 41.9-52.1). Of 445 patients in complete remission after 5 weeks of induction treatment, 191 were randomised: 95 patients to receive a late intensification course, and 96 to a control group. At a median follow-up of 42 (range 1-73) months, 60 patients in the treatment group and 57 controls were disease-free. DFS at 4 years did not differ between the two groups (60.9% [SE 5.2] for treatment group vs 57.0% [5.5] for controls; p=0.81). During the intensification phase, of 71 patients randomly assigned to the treatment group, and for whom toxicity data were available, 35 (49%) had infections, 21 (30%) patients had mucositis, 22 (31%) patients had toxic effects on the liver, and 2 (3%) had neurotoxicity. All types of rearrangements in the (mixed lineage leukaemia) MLL gene, very high white blood cell count, age of younger than 6 months, and a poor response to the prednisone prophase were independently associated with inferior outcomes. Interpretation Patients treated with our hybrid protocol, and especially those who responded poorly to prednisone, had higher EFS than most reported outcomes for treatment of infant ALL. Delayed intensification of chemotherapy did not benefit patients. C1 Sophia Childrens Univ Hosp, Erasmus MC, Dept Paediat Oncol & Haematol, NL-3015 GJ Rotterdam, Netherlands. Univ Med Ctr Schleswig Holstein, Kiel, Germany. Univ Milano Bicocca, Dept Clin Med & Prevent, Milan, Italy. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Sheffield Childrens Hosp, Sheffield, S Yorkshire, England. Univ Milano Bicocca, San Gerardo Hosp, Monza, Italy. Children Hosp Bambino Gesu, Rome, Italy. Argentina Hosp Pediat, Buenos Aires, DF, Argentina. Univ Helsinki, Helsinki, Finland. Hop St Louis, Paris, France. Med Univ Silesia, Zabrze, Poland. Hop Univ Enfants Reine Fabiola, Brussels, Belgium. Univ Hosp Hamburg Eppendorf, Hamburg, Germany. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Charles Univ Prague, Sch Med 2, Prague, Czech Republic. Univ Hosp Motol, Prague, Czech Republic. Hosp Roberto del Rio, Santiago, Chile. Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. St Anna Childrens Hosp, A-1090 Vienna, Austria. Womens & Childrens Hosp, Adelaide, SA, Australia. RP Pieters, R (reprint author), Sophia Childrens Univ Hosp, Erasmus MC, Dept Paediat Oncol & Haematol, Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. EM rob.picters@erasmusmc.nl RI Schrappe, Martin/A-8109-2010; Li, Chi Kong/J-8456-2013 FU Medical Research Council [G0300130] NR 31 TC 244 Z9 260 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JUL 21 PY 2007 VL 370 IS 9583 BP 240 EP 250 DI 10.1016/S0140-6736(07)61126-X PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 194MG UT WOS:000248347900028 PM 17658395 ER PT J AU Tang, XL Sharp, GC Jiang, SB AF Tang, Xiaoli Sharp, Greg C. Jiang, Steve B. TI Fluoroscopic tracking of multiple implanted fiducial markers using multiple object tracking SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID REAL-TIME TUMOR; TRANSTHORACIC NEEDLE-BIOPSY; PULMONARY NODULES; RADIATION-THERAPY; RADIOTHERAPY; MOTION; SYSTEM; PNEUMOTHORAX; RESPIRATION; PROSTATE AB When treating mobile tumors using techniques such as beam gating or beam tracking, precise localization of tumor position is required, which is often realized by fluoroscopically tracking implanted fiducial markers. Multiple markers placed inside or near a tumor are often preferred to a single marker for the sake of accuracy. In this work, we propose a marker tracking system that can track multiple markers simultaneously, without confusing them, and that is also robust enough to continue tracking even when the markers are moving behind bony anatomy. The integrated radiotherapy imaging system (IRIS), developed at the Massachusetts General Hospital (MGH), was used to take fluoroscopy videos for marker tracking. The tracking system integrates marker detection with a multiple object tracking process, inspired by the multiple hypothesis marker tracking (MHT) process. It also utilizes breathing pattern information to help tracking. Four criteria are used to identify tracking failure, and when tracking failure occurs, the system can immediately inform the user. (In the clinical environment, the system would immediately disable the treatment beam.) In this paper, two liver patients with implanted fiducial markers were studied, and the studies were performed retrospectively to assess the effectiveness of the new tracking system. For both patients, LAT and AP fluoroscopic videos were studied. In order to better test the proposed tracking system, artificial markers were added around the real markers to disturb the tracking of the real markers. The performance of the proposed system was compared to that of a conventional tracking system (one that did not use multiple object tracking). The performance of the new system was also investigated with and without consideration of the breathing pattern information. We found that the conventional tracking system can easily miss tracking markers in the presence of artificial markers, and it cannot detect the tracking failures. On the other hand, our proposed system can track markers well and can also successfully detect tracking failures. Failure rate was calculated on a per-frame-per-marker basis for the proposed tracking system. When the system considered breathing pattern information, it had a 0% failure rate 75% of the time and 0.4% failure rate 25% of the time. However, when the system did not consider breathing patterns, it had a much higher failure rate, in the range of 1.2% - 12%. Both examples of the proposed system yielded low e(95) (the maximum marker tracking error at 95% confidence level) - less than 1.5 mm. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tang, XL (reprint author), Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. EM xitang@ucsd.edu FU NCI NIH HHS [1 R21 CA110177 A 01A] NR 28 TC 56 Z9 58 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUL 21 PY 2007 VL 52 IS 14 BP 4081 EP 4098 DI 10.1088/0031-9155/52/14/005 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 180XC UT WOS:000247400000005 PM 17664596 ER PT J AU Grotenbreg, GM Nicholson, MJ Fowler, KD Wilbuer, K Octavio, L Yang, MX Chakraborty, AK Ploegh, HL Wucherpfennig, KW AF Grotenbreg, Gijsbert M. Nicholson, Melissa J. Fowler, Kevin D. Wilbuer, Kathrin Octavio, Leah Yang, Maxine Chakraborty, Arup K. Ploegh, Hidde L. Wucherpfennig, Kai W. TI Empty class II major histocompatibility complex created by peptide photolysis establishes the role of DM in peptide association SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HLA-DR MOLECULES; RESTRICTED ANTIGEN PRESENTATION; MYELIN BASIC-PROTEIN; INVARIANT CHAIN; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; MHC MOLECULES; BINDING; DISSOCIATION; EXPRESSION AB DM catalyzes the exchange of peptides bound to Class II major histocompatibility complex (MHC) molecules. Because the dissociation and association components of the overall reaction are difficult to separate, a detailed mechanism of DM catalysis has long resisted elucidation. UV irradiation of DR molecules loaded with a photocleavable peptide (caged Class II MHC molecules) enabled synchronous and verifiable evacuation of the peptide-binding groove and tracking of early binding events in real time by fluorescence polarization. Empty DR molecules generated by photocleavage rapidly bound peptide but quickly resolved into species with substantially slower binding kinetics. DM formed a complex with empty DR molecules that bound peptide with even faster kinetics than empty DR molecules just having lost their peptide cargo. Mathematical models demonstrate that the peptide association rate of DR molecules is substantially higher in the presence of DM. We therefore unequivocally establish that DM contributes directly to peptide association through formation of a peptide-loading complex between DM and empty Class II MHC. This complex rapidly acquires a peptide analogous to the MHC class I peptide-loading complex. C1 Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Wucherpfennig, KW (reprint author), 44 Binney St, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu FU NIAID NIH HHS [P01 AI045757, P01 AI071195, R01 AI057493]; NIH HHS [DP1 OD001022] NR 42 TC 31 Z9 31 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 JUL 20 PY 2007 VL 282 IS 29 BP 21425 EP 21436 DI 10.1074/jbc.M702844200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190GP UT WOS:000248047500070 PM 17525157 ER PT J AU Chakravarti, A DeSilvio, M Zhang, M Grignon, D Rosenthal, S Asbell, SO Hanks, G Sandler, HM Khor, LY Pollack, A Shipley, W AF Chakravarti, Arnab DeSilvio, Michelle Zhang, Min Grignon, David Rosenthal, Seth Asbell, Sucha O. Hanks, Gerald Sandler, Howard M. Khor, Li-Yan Pollack, Alan Shipley, William TI Prognostic value of p16 in locally advanced prostate cancer: A study based on Radiation Therapy Oncology Group protocol 9202 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANDROGEN DEPRIVATION; FACTOR EXPRESSION; RB/E2F PATHWAY; LUNG-CANCER; CARCINOMA; ANGIOGENESIS; APOPTOSIS; TUMORS; ROLES AB Purpose Deregulation of the retinoblastoma ( RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods RTOG 9202 was a phase III randomized study comparing long-term ( LT) versus short-term ( ST) androgen-deprivation therapy ( AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry ( IHC). IHC staining was scored quantitatively using an image analysis system. Results On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases ( P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact ( high levels of immunostaining) p16 ( mean p16 index > 81.3%), LTAD plus radiotherapy ( RT) significantly improved prostate cancer survival ( PCS) compared with STAD plus RT ( P = .0008) and reduced the frequency of distant metastasis ( P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss ( low levels of immunostaining, mean p16 index > 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD ( P < .0001) primarily by decreasing the frequency of local progression ( P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Amer Coll Radiol, Reston, VA USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Harper Grace Hosp, Detroit, MI USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Radiol Assoc Sacramento, Sacramento, CA USA. Fox Chase Canc Ctr, Philadelphia, PA USA. RP Chakravarti, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org FU NCI NIH HHS [R01 CA101984-01, R01 CA101984, R01 CA101984-05, U10 CA021661, U10 CA032115, U10 CA037422, U10CA21661, U10CA32115, U10CA37422] NR 19 TC 33 Z9 34 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 JUL 20 PY 2007 VL 25 IS 21 BP 3082 EP 3089 DI 10.1200/JCO.2006.08.4152 PG 8 WC Oncology SC Oncology GA 200DJ UT WOS:000248743800016 PM 17634487 ER PT J AU Metzger, ML Stewart, CF Freeman, BB Billups, CA Hoffer, FA Wu, JR Coppes, MJ Grant, R Chintagumpala, M Mullen, EA Alvarado, C Daw, NC Dome, JS AF Metzger, Monika L. Stewart, Clinton F. Freeman, Burgess B., III Billups, Catherine A. Hoffer, Fredric A. Wu, Jianrong Coppes, Max J. Grant, Ronald Chintagumpala, Murali Mullen, Elizabeth A. Alvarado, Carlos Daw, Najat C. Dome, Jeffrey S. TI Topotecan is active against Wilms' tumor: Results of a multi-institutional phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Congress of the International-Society-of-Pediatric-Oncology CY SEP 17-21, 2006 CL Geneva, SWITZERLAND SP Int Soc Pediat Oncol ID STEM-CELL RESCUE; PEDIATRIC-ONCOLOGY-GROUP; GUIDED DOSING APPROACH; SOLID TUMORS; FRENCH-SOCIETY; INITIAL TREATMENT; ACTINOMYCIN-D; CHILDREN; RECURRENT; EXPERIENCE AB Purpose A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor. Patients and Methods Patients with favorable histology Wilms' tumor ( FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor ( AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve ( AUC) of 80 +/- 10 ng/mL*h. Tumor responses were measured after two cycles of treatment. Results Thirty-seven patients ( 26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan ( range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m(2) ( range, 0.7 to 3.2 mg/m(2)). Of 25 assessable patients with FHWT, 12 had partial response ( PR), six had stable disease (SD), and seven had progressive disease ( PD), for an overall response rate of 48% ( 95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia ( median duration, 13 days) and thrombocytopenia ( median duration, 7.5 days). Conclusion Topotecan administered on a protracted schedule is active against recurrent FHWT. Inclusion of topotecan in front-line clinical trials for patients with recurrent Wilms' tumor should be considered. C1 Childrens Natl Med Ctr, Ctr Camc & Blood Disorders, Div Oncol, Washington, DC 20010 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hlthcare, Atlanta, GA USA. Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Dome, JS (reprint author), Childrens Natl Med Ctr, Ctr Camc & Blood Disorders, Div Oncol, 111 Michigan Ave,NW, Washington, DC 20010 USA. EM jdome@cnmc.org FU NCI NIH HHS [CA-23099, CA-21765] NR 38 TC 27 Z9 28 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 JUL 20 PY 2007 VL 25 IS 21 BP 3130 EP 3136 DI 10.1200/JCO.2007.10.9298 PG 7 WC Oncology SC Oncology GA 200DJ UT WOS:000248743800023 PM 17634492 ER PT J AU Kieran, MW Packer, RJ Onar, A Blaney, SM Phillips, P Pollack, IF Geyer, JR Gururangan, S Banerjee, A Goldman, S Turner, CD Belasco, JB Broniscer, A Zhu, Y Frank, E Kirschmeier, P Statkevich, P Yver, A Boyett, JM Kun, LE AF Kieran, Mark W. Packer, Roger J. Onar, Arzu Blaney, Susan M. Phillips, Peter Pollack, Ian F. Geyer, J. Russell Gururangan, Sri Banerjee, Anu Goldman, Stewart Turner, Christopher D. Belasco, Jean B. Broniscer, Alberto Zhu, Yali Frank, Emily Kirschmeier, Paul Statkevich, Paul Yver, Antoine Boyett, James M. Kun, Larry E. TI Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: A Pediatric Brain Tumor Consortium Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FARNESYL TRANSFERASE INHIBITOR; ADVANCED SOLID TUMORS; PROTEIN TRANSFERASE; ANTITUMOR-ACTIVITY; HUMAN HEPATOCYTES; XENOGRAFT MODELS; HUMAN-LIVER; SCH-66336; R115777; CANCER AB Purpose A dose-escalation phase I and pharmacokinetic study of the farnesyltransferase inhibitor lonafarnib ( SCH66336) was conducted in children with recurrent or progressive CNS tumors. Primary objectives were to estimate the maximum-tolerated dose ( MTD) and to describe the dose-limiting toxicities ( DLTs) and pharmacokinetics of lonafarnib. Farnesylation inhibition of HDJ-2 in peripheral blood was also measured. Patients and Methods Lonafarnib was administered orally twice daily at dose levels of 70, 90, 115, 150, and 200 mg/m(2)/dose bid. A modified continual reassessment method ( CRM) was used to estimate the MTD based on actual dosages of lonafarnib administered and toxicities observed during the initial 4 weeks of treatment. Results Fifty-three children with progressive or recurrent brain tumors were enrolled, with a median age of 12.2 years ( range, 3.9 to 19.5 years). Dose-limiting pneumonitis or myelosuppression was observed in three of three patients at the 200 mg/m(2)/dose level. A relatively constant DLT rate at the 70, 90, and 115 mg/m2/dose levels resulted in a recommended phase II dose of 115 mg/m(2)/dose. Significant diarrhea did not occur with prophylactic loperamide. Both radiographic response ( one anaplastic astrocytoma) and stable disease ( one medulloblastoma, two high-grade and four low-grade gliomas, one ependymoma, and one sarcoma) were noted, and seven patients remained on treatment for 1 year or longer. Conclusion Although the estimated MTD by the CRM model was 98.5 mg/m(2)/dose, because of the relatively constant observed DLT rate at the lower four dose levels, the recommended phase II dose of lonafarnib is 115 mg/m(2)/dose administered twice daily by mouth with concurrent loperamide. C1 Childrens Hosp, Dana Farber Canc Inst, Pediat Neuro Oncol, Boston, MA 02115 USA. Childrens Natl, Med Ctr, Washington, DC USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Baylor Coll Med, Houston, TX 77030 USA. Childrens Hosp, Philadelphia, PA 19104 USA. Childrens Hosp, Pittsburgh, PA 15213 USA. Childrens Hosp, Reg Med Ctr, Seattle, WA USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Mem Hosp, Chicago, IL USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Kieran, MW (reprint author), Childrens Hosp, Dana Farber Canc Inst, Pediat Neuro Oncol, 44 Binney St,Room SW331, Boston, MA 02115 USA. EM mark_Kieran@dfci.Harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [U01 CA81457] NR 36 TC 33 Z9 34 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 JUL 20 PY 2007 VL 25 IS 21 BP 3137 EP 3143 DI 10.1200/JCO.2006.09.4243 PG 7 WC Oncology SC Oncology GA 200DJ UT WOS:000248743800024 PM 17634493 ER PT J AU Chen, YB Yu, HB Gillani, A Brown, JR AF Chen, Yi-Bin Yu, Hongbo Gillani, Aqeel Brown, Jennifer R. TI AIDS-associated plasmablastic lymphoma presenting at the insertion site of a peritoneal dialysis catheter SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CENTRAL VENOUS CATHETER; ACTIVE ANTIRETROVIRAL THERAPY; MULTIPLE-MYELOMA; TUMOR-METASTASIS; ORAL-CAVITY; HIV; LOCALIZATION; PATIENT; TRAUMA; TRACT C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Glen Falls Hosp Canc Ctr, Glens Falls, NY USA. RP Chen, YB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 TC 5 Z9 5 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 JUL 20 PY 2007 VL 25 IS 21 BP 3176 EP 3178 DI 10.1200/JCO.2007.12.0154 PG 3 WC Oncology SC Oncology GA 200DJ UT WOS:000248743800031 PM 17634499 ER PT J AU Wang, JH Hu, WD Cai, S Lee, B Song, J Chen, Y AF Wang, Jianghai Hu, Weidong Cai, Sheng Lee, Brian Song, Jing Chen, Yuan TI The intrinsic affinity between E2 and the cys domain of E1 in ubiquitin-like modifications SO MOLECULAR CELL LA English DT Article ID ACTIVATING ENZYME; STRUCTURAL BASIS; CONJUGATION; BINDING; SITE; IDENTIFICATION; RESTRAINTS; PROTEINS; INSIGHTS; SYSTEM AB Ubiquitin-like modifications, which are carried out by similar biochemical mechanisms, regulate nearly every aspect of cellular function. Despite the recent advancements in characterizing their enzymology, our knowledge about the dynamic processes of these modifications is still fragmentary. In this study, we have uncovered an intrinsic affinity between the SUMO E2 and the Cys domain of SUMO E1. NMR studies in combination with paramagnetic spin labeling demonstrate that this interaction is mediated by previously unknown interfaces on both Ell and E2 and places the two catalytic Cys residues of the two enzymes in close proximity. Site-directed mutagenesis and enzymatic assays indicate that the interaction is fundamentally important for the transfer of SUMO from E1 to E2. Results from this study suggest that the interaction between E2 and the Cys domain of E1 participates in guiding the E2's translocation to E1's enzymatic active site in ubiquitin-like modifications. C1 City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. City Hope Natl Med Ctr, City Hope Summer Internship Program, Duarte, CA 91010 USA. City Hope Natl Med Ctr, City Hope Grad Sch, Duarte, CA 91010 USA. Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA. Marquette Univ, Dept Chem, Milwaukee, WI 53201 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Chen, Y (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. EM ychen@coh.org FU NCI NIH HHS [R01 CA094595, R01 CA094595-05, CA094595]; NIGMS NIH HHS [R01 GM074748, R01 GM074748-01A2, GM074748] NR 30 TC 38 Z9 41 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL 20 PY 2007 VL 27 IS 2 BP 228 EP 237 DI 10.1016/j.molcel.2007.05.023 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 195OD UT WOS:000248420600009 PM 17643372 ER PT J AU Harel, O Zhou, XH AF Harel, Ofer Zhou, Xiao-Hua TI Multiple imputation: Review of theory, implementation and software SO STATISTICS IN MEDICINE LA English DT Review DE multiple imputation; sensitivity and specificity; diagnostic tests ID PATTERN-MIXTURE MODELS; DATA AUGMENTATION; IMPUTED DATA; MISSING DATA; POSTERIOR DISTRIBUTIONS; INCOMPLETE DATA; DROP-OUT; TESTS; VERIFICATION; ESTIMATORS AB Missing data is a common complication in data analysis. In many medical settings missing data can cause difficulties in estimation, precision and inference. Multiple imputation (MI) (Multiple Imputation for Nonresponse in Surveys. Wiley: New York, 1987) is a simulation-based approach to deal with incomplete data. Although there are many different methods to deal with incomplete data, MI has become one of the leading methods. Since the late 1980s we observed a constant increase in the use and publication of MI-related research. This tutorial does not attempt to cover all the material concerning MI, but rather provides an overview and combines together the theory behind MI, the implementation of MI, and discusses increasing possibilities of the use of MI using commercial and free software. We illustrate some of the major points using an example from an Alzheimer disease (AD) study. In this AD study, while clinical data are available for all subjects, postmortem data are only available for the subset of those who died and underwent an autopsy. Analysis of incomplete data requires making unverifiable assumptions. These assumptions are discussed in detail in the text. Relevant S-Plus code is provided. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Harel, O (reprint author), Univ Connecticut, Dept Stat, 215 Glenbrook Rd Unit 4120, Storrs, CT 06269 USA. EM oharel@stat.uconn.edu FU AHRQ HHS [R01HS013105]; NHLBI NIH HHS [R01HL62567]; NIA NIH HHS [U01 AG016976, U01 AG16976]; NIMH NIH HHS [K01 MH087219] NR 59 TC 132 Z9 134 U1 1 U2 32 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 20 PY 2007 VL 26 IS 16 BP 3057 EP 3077 DI 10.1002/sim.2787 PG 21 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 187GX UT WOS:000247836700001 PM 17256804 ER PT J AU Wernig, M Meissner, A Foreman, R Brambrink, T Ku, MC Hochedlinger, K Bernstein, BE Jaenisch, R AF Wernig, Marius Meissner, Alexander Foreman, Ruth Brambrink, Tobias Ku, Manching Hochedlinger, Konrad Bernstein, Bradley E. Jaenisch, Rudolf TI In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; DEVELOPMENTAL REGULATORS; RETROVIRAL GENOMES; SOMATIC-CELLS; DNA; EXPRESSION; CLONING; DIFFERENTIATION; TRANSCRIPTION AB Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of 'customized' embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced in vitro through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells - derived from mouse fibroblasts - can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, 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, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Jaenisch, R (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM jaenisch@wi.mit.edu FU NIGMS NIH HHS [T32 GM007753] NR 34 TC 1665 Z9 1776 U1 27 U2 235 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 19 PY 2007 VL 448 IS 7151 BP 318 EP U2 DI 10.1038/nature05944 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 191GC UT WOS:000248118300050 PM 17554336 ER PT J AU Gudbjartsson, DF Arnar, DO Helgadottir, A Gretarsdottir, S Holm, H Sigurdsson, A Jonasdottir, A Baker, A Thorleifsson, G Kristjansson, K Palsson, A Blondal, T Sulem, P Backman, VM Hardarson, GA Palsdottir, E Helgason, A Sigurjonsdottir, R Sverrisson, JT Kostulas, K Ng, MCY Baum, L So, WY Wong, KS Chan, JCN Furie, KL Greenberg, SM Sale, M Kelly, P MacRae, CA Smith, EE Rosand, J Hillert, J Ma, RCW Ellinor, PT Thorgeirsson, G Gulcher, JR Kong, A Thorsteinsdottir, U Stefansson, K AF Gudbjartsson, Daniel F. Arnar, David O. Helgadottir, Anna Gretarsdottir, Solveig Holm, Hilma Sigurdsson, Asgeir Jonasdottir, Adalbjorg Baker, Adam Thorleifsson, Gudmar Kristjansson, Kristleifur Palsson, Arnar Blondal, Thorarinn Sulem, Patrick Backman, Valgerdur M. Hardarson, Gudmundur A. Palsdottir, Ebba Helgason, Agnar Sigurjonsdottir, Runa Sverrisson, Jon T. Kostulas, Konstantinos Ng, Maggie C. Y. Baum, Larry So, Wing Yee Wong, Ka Sing Chan, Juliana C. N. Furie, Karen L. Greenberg, Steven M. Sale, Michelle Kelly, Peter MacRae, Calum A. Smith, Eric E. Rosand, Jonathan Hillert, Jan Ma, Ronald C. W. Ellinor, Patrick T. Thorgeirsson, Gudmundur Gulcher, Jeffrey R. Kong, Augustine Thorsteinsdottir, Unnur Stefansson, Kari TI Variants conferring risk of atrial fibrillation on chromosome 4q25 SO NATURE LA English DT Article ID OF-FUNCTION MUTATION; FAMILIAL AGGREGATION; ISCHEMIC-STROKE; GENE; PREVALENCE; KCNQ1 AB Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria(1). It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality(2). Recent studies have provided evidence of a genetic contribution to AF(3-5). Mutations in potassium-channel genes have been associated with familial AF(6-10) but account for only a small fraction of all cases of AF(11,12). We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart(13-15). C1 deCODE Genet, IS-101 Reykjavik, Iceland. Landspitali Univ, Div Cardiol, Dept Med, IS-101 Reykjavik, Iceland. Akureyri Reg Hosp, Dept Med, IS-600 Akureyri, Iceland. Karolinska Univ Hosp, Dept Neurol, S-14186 Huddinge, Sweden. Chinese Univ Hong Kong, Dept Med & Therapeut, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gudbjartsson, DF (reprint author), deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland. EM daniel.gudbjartsson@decode.is; kstefans@decode.is RI Baum, Lawrence/B-1005-2013; Wong, Ka Sing Lawrence/N-3434-2015; Chan, Juliana /B-7918-2016; Ma, Ronald/C-2788-2009; Helgason, Agnar/K-1522-2015; Palsson, Arnar/M-2742-2015 OI Baum, Lawrence/0000-0002-5345-9355; Wong, Ka Sing Lawrence/0000-0002-2031-9866; Chan, Juliana /0000-0003-1325-1194; Ma, Ronald/0000-0002-1227-803X; Palsson, Arnar/0000-0002-6525-8112; Gudbjartsson, Daniel/0000-0002-5222-9857; Smith, Eric/0000-0003-3956-1668; FU NHLBI NIH HHS [R01 HL075431] NR 24 TC 432 Z9 446 U1 3 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUL 19 PY 2007 VL 448 IS 7151 BP 353 EP 357 DI 10.1038/nature06007 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 191GC UT WOS:000248118300058 PM 17603472 ER PT J AU Taqueti, VR AF Taqueti, Viviany R. TI Leaving against medical advice SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taqueti, VR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 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 JUL 19 PY 2007 VL 357 IS 3 BP 213 EP 215 DI 10.1056/NEJMp078046 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 191FH UT WOS:000248115100002 PM 17634456 ER PT J AU Chung, DC Yoon, SS Lauwers, GY Patel, D AF Chung, Daniel C. Yoon, Sam S. Lauwers, Gregory Y. Patel, Devanshi TI A woman with a family history of gastric and breast cancer - Hereditary diffuse gastric cancer syndrome due to germ-line E-cadherin mutation, with gastric intramucosal signet-ring-cell carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; PROPHYLACTIC TOTAL GASTRECTOMY; CARRIERS; MANAGEMENT; RECONSTRUCTION; GENETICS; BRCA1; RISK C1 Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. NR 34 TC 27 Z9 27 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 JUL 19 PY 2007 VL 357 IS 3 BP 283 EP 291 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 191FH UT WOS:000248115100011 PM 17634464 ER PT J AU Ramaswamy, S AF Ramaswamy, Sridhar TI Rational design of cancer-drug combinations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. FU NCI NIH HHS [K08 CA100339, K08 CA100339-05] NR 1 TC 35 Z9 36 U1 0 U2 5 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 JUL 19 PY 2007 VL 357 IS 3 BP 299 EP 300 DI 10.1056/NEJMcibr072593 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 191FH UT WOS:000248115100014 PM 17634467 ER PT J AU Cushman, WC Grimm, RH Cutler, JA Evans, GW Capes, S Corson, MA Sadler, LS Alderman, MH Peterson, K Bertoni, A Basile, JN AF Cushman, William C. Grimm, Richard H., Jr. Cutler, Jeffrey A. Evans, Gregory W. Capes, Sarah Corson, Marshall A. Sadler, Laurie S. Alderman, Michael H. Peterson, Kevin Bertoni, Alain Basile, Jan N. CA ACCORD Study Grp TI Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LIPID-LOWERING TREATMENT; JOINT NATIONAL COMMITTEE; MICROVASCULAR COMPLICATIONS; HYPERTENSIVE PATIENTS; ANTIHYPERTENSIVE TREATMENT; SYSTOLIC HYPERTENSION; DISEASE RISK; 7TH REPORT; OUTCOMES; MELLITUS AB The Action to Control Cardiovascular Disease in Diabetes (ACCORD) blood pressure trial is an unmasked, open-label, randomized trial with a sample size of 4,733 participants. This report describes the rationale, design, and methods of the blood pressure interventions in ACCORD. Participants eligible for the blood pressure trial are randomized to 1 of 2 groups with different treatment goals: systolic blood pressure < 120 mm Hg for the more intensive goal and systolic blood pressure < 140 mm Hg for the less intensive goal. The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease (CVD) event, specifically nonfatal myocardial infarction or stroke, or cardiovascular death during a follow-up period ranging from 4-8 years. The ACCORD blood pressure trial should provide the first definitive clinical trial data on the possible benefit of treating to a more aggressive systolic blood pressure goal in reducing CVD events in patients with diabetes mellitus. (c) 2007 Elsevier Inc. All rights reserved. C1 Vet Affairs Med Ctr, Memphis, TN USA. Hennepin Cty Med Ctr, Berman Ctr Outcomes & Clin Res, Div Clin Epidemiol, Minneapolis, MN 55415 USA. NHLBI, Div Cardiovasc Dis, Vasc Biol & Hypertens Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. McMaster Univ, Dept Med, Hamilton, ON, Canada. Univ Washington, Med Ctr, Dept Med, Div Cardiol, Seattle, WA 98195 USA. St Vincent Charity Hosp, Lipid Res Ctr, Cleveland, OH USA. Albert Einstein Coll Med, Dept Med & Epidemiol, Bronx, NY 10467 USA. Univ Minnesota, Phalen Village Clin, Minneapolis, MN USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Cushman, WC (reprint author), Vet Affairs Med Ctr, Prevent Med Sect 111Q, 1030 Jefferson Ave, Memphis, TN 38104 USA. EM william.cushman@va.gov OI Peterson, Kevin/0000-0002-6914-8586 FU NHLBI NIH HHS [N01-HC-95183, Y1-HC-9035, N01-HC-95178, N01-HC-95182, N01-HC-95184, N01-HC-95179, N01-HC-95181, N01-HC-95180, Y1-HC-1010] NR 33 TC 17 Z9 18 U1 0 U2 2 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 JUL 18 PY 2007 VL 99 IS 12A SU S BP 44I EP 55I DI 10.1016/j.amjcard.2007.03.005 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 188RV UT WOS:000247937900005 PM 17599425 ER PT J AU Ohashi, R Takahashi, F Cui, R Yoshioka, M Gu, T Sasaki, S Tominaga, S Nishio, K Tanabe, KK Takahashi, K AF Ohashi, Rina Takahashi, Fumiyuki Cui, Ri Yoshioka, Masakata Gu, Tao Sasaki, Shinichi Tominaga, Shigeru Nishio, Kazuto Tanabe, Kenneth K. Takahashi, Kazuhisa TI Interaction between CD44 and hyaluronate induces chemoresistance in non-small cell lung cancer cell SO CANCER LETTERS LA English DT Article DE hyaluronate; non-small cell lung cancer; chemoresistance; CD44s; MRP2 ID EXTRACELLULAR-MATRIX PROTEINS; DRUG-RESISTANCE; CARCINOMA CELLS; CISPLATIN; SENSITIVITY; ACCUMULATION; EXPRESSION; ADHESION; LINES; MICROENVIRONMENT AB CD44s is a principle hyaluronate (HA) receptor and has been reported to play an important role in cancer cell invasion and metastasis. The aim of our study is to determine if the interaction between HA and CD44s influences in vitro chemosensitivity of non-small cell lung cancer (NSCLC). NSCLC cell line, H322 cells, transfected with the CD44s gene (H322/ CD44s) cultured on HA coated plates were more resistant to cisplatin (CDDP) than that on bovine serum albumin. Multidrug resistance protein2 (MRP2) expression was induced in H322/CD44s cells cultured on HA. MRP2 inhibitor, MK571, not only suppressed MRP2 expression but also reversed CDDP resistance. These results suggest that the interaction between CD44s and HA play a pivotal role in acquired resistance to CDDP in NSCLC and MRP2 could be involved in this potential mechanism. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, Tokyo 1138421, Japan. Juntendo Univ, Sch Med, Res Inst Dis Old Ages, Tokyo 1138421, Japan. Natl Inst Canc Res, Div Pharmacol, Chuo Ku, Tokyo 1040045, Japan. Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP Ohashi, R (reprint author), Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan. EM rinaohas@med.juntendo.ac.jp RI cui, ri/P-8507-2014 OI cui, ri/0000-0001-6202-8779 NR 30 TC 48 Z9 51 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 18 PY 2007 VL 252 IS 2 BP 225 EP 234 DI 10.1016/j.canlet.2006.12.025 PG 10 WC Oncology SC Oncology GA 182OM UT WOS:000247513900007 PM 17276588 ER PT J AU Wu, K Feskanich, D Fuchs, CS Willett, WC Hollis, BW Giovannucci, EL AF Wu, Kana Feskanich, Diane Fuchs, Charles S. Willett, Walter C. Hollis, Bruce W. Giovannucci, Edward L. TI A nested case-control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN COLONIC MUCOSA; VITAMIN-D-RECEPTOR; SERUM 25-HYDROXYVITAMIN-D; D REDUCE; CALCIUM; EXPRESSION; WOMEN; MEN; METABOLISM; D-3-1-ALPHA-HYDROXYLASE AB Background Low vitamin D status has long been implicated in colorectal carcinogenesis. We investigated this relationship in a nested case-control study within the Health Professionals Follow-up Study (HPFS), a large ongoing study of male health professionals living in the United States. Methods Between 1993 and 2002, 179 colorectal cancer patients were diagnosed and matched to 356 control subjects by age and by month and year of blood collection. Results were also pooled with previously published results from the Nurses' Health Study (NHS) cohort, a large female cohort. Conditional logistic regression was used to analyze the association between plasma 25-hydroxyvitamin D [25(OH)D] and colorectal cancer, and pooled estimates were calculated using the method of DerSimonian and Laird. All statistical tests were two-sided. Results In the HPFS, we observed a non-statistically significant inverse association between higher plasma 25(OH)D concentration and risk of colorectal cancer and a statistically significant inverse association for colon cancer (highest versus lowest quintile: odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.89; P-trend = .005). After pooling the results from the HPFS and NHS, higher plasma 25(OH)D concentrations were statistically significantly associated with decreased risks of both colorectal cancer (highest versus lowest quintile, OR = 0.66, 95% CI = 0.42 to 1.05; P-trend = .01) and colon cancer (highest versus lowest quintile, OR = 0.54, 95% CI = 0.34 to 0.86; P-trend = .002). Inverse associations with plasma 25(OH)D concentration did not differ by location of colon cancer (proximal versus distal), but the number of patients was small and none of the associations was statistically significant. Opposite relationships between plasma 25(OH)D levels and risk of rectal cancers were found among men (positive) and women (inverse). Conclusion Our data provide additional support for the inverse association between vitamin D and colorectal and, in particular, colon cancer risk. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. RP Wu, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM kana.wu@channing.harvard.edu FU NCI NIH HHS [CA 055075, CA87979] NR 43 TC 150 Z9 152 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 18 PY 2007 VL 99 IS 14 BP 1120 EP 1129 DI 10.1093/jnci/djm038 PG 10 WC Oncology SC Oncology GA 200BD UT WOS:000248738000013 PM 17623801 ER PT J AU Guzman-Marin, R Suntsova, N Bashir, T Szymusiak, R McGinty, D AF Guzman-Marin, Ruben Suntsova, Natalia Bashir, Tariq Szymusiak, Ronald McGinty, Dennis TI Cell proliferation in the dentate gyrus of the adult rat fluctuates with the light-dark cycle SO NEUROSCIENCE LETTERS LA English DT Article DE cell proliferation; dentate gyrus; hippocampus; circadian; BrdU ID NEUROGENESIS; SLEEP; HIPPOCAMPUS; PERIOD2; RHYTHMS AB This study measured cell proliferation in the hippocampal dentate gyrus in the adult rat at different times within a 12:12 It light-dark cycle. The experiments were conducted in animals living in either a complex environment or in standard lab cages. A single dose of the thymidine analog 5-Bromo-2'-deoxyuridine (BrdU) was injected 2 h before animals were sacrificed either 4, 11, 16, or 23 h after the beginning of the light phase of the light-dark cycle (designated ZT0). In both studies, we found a significant increase in the number of BrdU-positive cells in the subgranular cell layer (SGZ) following BrdU administration at ZT9 and sacrifice at ZT11, compared to other circadian times examined. BrdU administration at ZT9 was timed to primarily identify proliferating cells that were in the S phase of the cell cycle during the light phase. Our results suggest that cell proliferation is enhanced either by sleep or by other variables coupled to the light phase of the circadian cycle. Published by Elsevier Ireland Ltd. 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, 151A3,16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [P50 HL060296, HL 60296, P50 HL060296-090010]; NIMH NIH HHS [R01 MH075076, R01 MH075076-01A2]; PHS HHS [075076] NR 17 TC 21 Z9 21 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 18 PY 2007 VL 422 IS 3 BP 198 EP 201 DI 10.1016/j.neulet.2007.06.022 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 203MV UT WOS:000248979600010 PM 17611030 ER PT J AU Baena, A Mootnick, AR Falvo, JV Tsytsykova, AV Ligeiro, F Diop, OM Brieva, C Gagneux, P O'Brien, SJ Ryder, OA Goldfeld, AE AF Baena, Andres Mootnick, Alan R. Falvo, James V. Tsytsykova, Alla V. Ligeiro, Filipa Diop, Ousmane M. Brieva, Claudia Gagneux, Pascal O'Brien, Stephen J. Ryder, Oliver A. Goldfeld, Anne E. TI Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity SO PLOS ONE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; SINGLE-NUCLEOTIDE POLYMORPHISMS; COMPARATIVE SEQUENCE-ANALYSIS; TRANSCRIPTION FACTOR-BINDING; MONKEY SAIMIRI-SCIUREUS; NEW-WORLD MONKEYS; DNA EVIDENCE; EXPRESSION PATTERNS; MOLECULAR PHYLOGENY AB Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance. Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type-and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF. C1 [Baena, Andres; Falvo, James V.; Tsytsykova, Alla V.; Ligeiro, Filipa; Goldfeld, Anne E.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Mootnick, Alan R.] Gibbon Conservat Ctr, Santa Clarita, CA USA. [Diop, Ousmane M.] Inst Pasteur, Lab Retrovirol, Dakar, Senegal. [Brieva, Claudia] Univ Nacl Colombia, Fac Med Vet & Zootecn, Unidad Rescate & Rehabil Anim Silvestres, Bogota, Colombia. [Gagneux, Pascal] Univ Calif San Diego, Dept Med & Cellular & Mol Med, Project Explaining Origin Humans, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA. [O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Ryder, Oliver A.] Zool Soc San Diego, San Diego, CA USA. [Ryder, Oliver A.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM goldfeld@cbrinstitute.org FU NIH [GM076685, HL59838]; NSF [0094993] FX This work was supported by grants from the NIH to A. E. G. (GM076685 and HL59838) and an NSF grant (0094993) to O.A.R. NR 111 TC 17 Z9 17 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 18 PY 2007 VL 2 IS 7 AR e621 DI 10.1371/journal.pone.0000621 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10GI UT WOS:000207452100011 PM 17637837 ER PT J AU Kaye, DM Preovolos, A Marshall, T Byrne, M Hoshijima, M Hajjar, R Mariani, JA Pepe, S Chien, KR Power, JM AF Kaye, David M. Preovolos, Arthur Marshall, Tanneale Byrne, Melissa Hoshijima, Masahiko Hajjar, Roger Mariani, Justin A. Pepe, Salvatore Chien, Kenneth R. Power, John M. TI Percutaneous cardiac recirculation-mediated gene TranSimer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; DILATED CARDIOMYOPATHY; CONTRACTILE DYSFUNCTION; INTRACORONARY DELIVERY; ADENOASSOCIATED VIRUS; CYCLOPIAZONIC ACID; THERAPY; CALCIUM; EXPRESSION; MYOCARDIUM AB Objectives The purpose of this study was to develop a clinically applicable high-efficiency percutaneous means of therapeutic gene delivery to the failing heart. Background Substantial advances in the understanding of the cellular and molecular basis of heart failure (HF) have recently fostered interest in the potential utility of gene and cell therapy as novel therapeutic approaches. However, successful clinical translation is currently limited by the lack of safe, efficient, and selective delivery systems. Methods We developed a novel percutaneous closed-loop recirculatory system that provides homogeneous myocardial delivery for gene transfer in the failing large animal heart. After 4 weeks' rapid pacing in adult sheep to induce HF, the animals were randomly allocated to receive either adenovirus expressing a pseudophosphorylated mutant (AdS16E) of phospholamban (PLN) or Ad-beta-galactosidase (AdLacZ). Results Two weeks after gene delivery, in the presence of continued pacing, left ventricular (LV) ejection fraction had significantly improved in the AdS16E-treated animals (27 +/- 3 % to 50 +/- 4 %; p < 0.001), whereas a further decline occurred in the AdLacZ group (34 +/- 4 % to 27 +/- 3 %; p < 0.05). In conjunction, AdS16E delivery resulted in significant reductions in LV filling pressures and end-diastolic diameter (both p < 0.05). In conjunction, AdS16E-treated animals showed significant improvement in the expression of PLN and Ca2+-adenosine triphosphatase activity. In separate animals, recirculating AdLacZ delivery was shown to achieve superior myocardial gene expression in contrast to intracoronary delivery and was associated with lower systemic expression. Conclusions We report the development of a novel closed-loop system for cardiac gene therapy. Using this approach delivery of AdS16E reversed HF progression in a large animal HF model. C1 Baker Heart Res Inst, Wynn Dept Metab Cardiol, Melbourne, Vic 8008, Australia. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. RP Kaye, DM (reprint author), Baker Heart Res Inst, Wynn Dept Metab Cardiol, POB 6492,St Kilda Rd Cent, Melbourne, Vic 8008, Australia. EM david.kaye@baker.edu.au RI Mariani, Justin/D-2241-2013 OI Mariani, Justin/0000-0002-9283-1551 NR 46 TC 83 Z9 87 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 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 17 PY 2007 VL 50 IS 3 BP 253 EP 260 DI 10.1016/j.jacc.2007.03.047 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 192YY UT WOS:000248241200008 PM 17631218 ER PT J AU Hayden, KM Zandi, PP Khachaturian, AS Szekely, CA Fotuhi, M Norton, MC Tschanz, JT Pieper, CF Corcoran, C Lyketsos, CG Breitner, JCS Welsh-Bohmer, KA AF Hayden, K. M. Zandi, P. P. Khachaturian, A. S. Szekely, C. A. Fotuhi, M. Norton, M. C. Tschanz, J. T. Pieper, C. F. Corcoran, C. Lyketsos, C. G. Breitner, J. C. S. Welsh-Bohmer, K. A. CA Cache County Investigators TI Does NSAID use modify cognitive trajectories in the elderly? The Cache county study SO NEUROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HORMONE REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; CONTROLLED-TRIAL; OLDER WOMEN; DECLINE; AD; PLACEBO; ANTAGONISTS; PREVENTION AB Background: Epidemiologic studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for the prevention of Alzheimer disease (AD). By contrast, clinical trials have not supported NSAID use to delay or treat AD. Few studies have evaluated cognitive trajectories of NSAID users over time. Methods: Residents of Cache County, UT, aged 65 or older on January 1, 1995, were invited to participate in the study. At baseline, participants provided a detailed inventory of their medications and completed a revised Modified Mini-Mental State Examination (3MS). Participants (n = 3,383) who were cognitively normal at baseline were re-examined after 3 and 8 years. The association between NSAID use and 3MS scores over time was estimated using random effects modeling. Results: Associations depended upon when NSAIDs were started and APOE genotype. In participants who started NSAID use prior to age 65, those with no APOE epsilon 4 alleles performed similarly to nonusers (a difference of 0.10 points per year; p = 0.19), while those with one or more epsilon 4 allele(s) showed more protection (0.40 points per year; p = 0.0005). Among participants who first used NSAIDs at or after age 65, those with one or more epsilon 4 alleles had higher baseline scores (0.95 points; p = 0.03) but did not show subsequent difference in change in score over time (0.06 points per year; p = 0.56). Those without an epsilon 4 allele who started NSAID use after age 65 showed greater decline than nonusers (-0.16 points per year; p = 0.02). Conclusions: Nonsteroidal anti-inflammatory drug use may help to prevent cognitive decline in older adults if started in midlife rather than late life. This effect may be more notable in those who have one or more APOE = 4 alleles. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. Khachaturian & Associates Inc, Baltimore, MD USA. Sinai Hosp, Baltimore, MD 21215 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Duke Univ, Dept Biometry & Bioinformat, Durham, NC USA. Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hayden, KM (reprint author), Joseph & Kathleen Bryan ADRC, DUMC, 2200 W Main St,Suite A-200, Durham, NC 27705 USA. EM khayden@duke.edu RI Szekely, Christine/C-1342-2009; Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012; OI Hayden, Kathleen/0000-0002-7745-3513; Fotuhi, Majid/0000-0002-0980-1176; Schwartz, Sarah/0000-0001-9980-7493 FU NIA NIH HHS [R01 AG011380, R01-AG11380, T32-AG00029]; NIMH NIH HHS [T32-MH14592] NR 28 TC 71 Z9 75 U1 0 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 JUL 17 PY 2007 VL 69 IS 3 BP 275 EP 282 DI 10.1212/01.wnl.0000265223.25679.2a PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 190LN UT WOS:000248060400009 PM 17636065 ER PT J AU Jager, S Handschin, C Pierre, J Spiegelman, BM AF Jaeger, Sibylle Handschin, Christoph St.-Pierre, Julie Spiegelman, Bruce M. TI AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1 alpha SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitochondria; respiration ID FATTY-ACID OXIDATION; PDK4 GENE-EXPRESSION; TRANSCRIPTIONAL COACTIVATOR; MITOCHONDRIAL BIOGENESIS; METFORMIN INCREASES; RAT EPITROCHLEARIS; METABOLIC-CONTROL; ENZYME-ACTIVITIES; ERR-ALPHA; PGC-1 AB Activation of AMP-activated kinase (AMPK) in skeletal muscle increases glucose uptake, fatty acid oxidation, and mitochondrial biogenesis by increasing gene expression in these pathways. However, the transcriptional components that are directly targeted by AMPK are still elusive. The peroxisome-proliferator-activated receptor gamma coactivator 1a (PGC-1 alpha) has emerged as a master regulator of mitochondrial biogenesis; furthermore, it has been shown that PGC-1 alpha gene expression is induced by exercise and by chemical activation of AMPK in skeletal muscle. Using primary muscle cells and mice deficient in PGC-1a, we found that the effects of AMPK on gene expression of glucose transporter 4, mitochondrial genes, and PGC-1 alpha itself are almost entirely dependent on the function of PGC-1a protein. Furthermore, AMPK phosphorylates PGC-1a directly both in vitro and in cells. These direct phosphorylations of the PGC-1a protein at threonine-177 and serine-538 are required for the PGC-la-dependent induction of the PGC-1 alpha promoter. These data indicate that AMPK phosphorylation of PGC-1a initiates many of the important gene regulatory functions of AMPK in skeletal muscle. C1 Univ Montreal, Inst Rech & Immunol & Cancerol, Montreal, PQ H3C 3J7, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Univ Zurich, Inst Physiol, CH-8006 Zurich, Switzerland. EM bruce-spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK54477, P30 DK040561, P30 DK040561-12, R01 DK054477, R56 DK054477] NR 56 TC 863 Z9 901 U1 12 U2 84 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 JUL 17 PY 2007 VL 104 IS 29 BP 12017 EP 12022 DI 10.1073/pnas.0705070104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 192KA UT WOS:000248199200029 PM 17609368 ER PT J AU Song, BB Chen, WL Marvizon, JCG AF Song, Bingbing Chen, Wenling Marvizon, Juan Carlos G. TI Inhibition of opioid release in the rat spinal cord by serotonin 5-HT1A receptors SO BRAIN RESEARCH LA English DT Article DE 5-HT1A receptor; dorsal horn; enkephalin; internalization; Mu-opioid receptor; serotonin ID DORSAL-HORN NEURONS; ENKEPHALIN-DEGRADING ENZYMES; MEDIAL PREOPTIC NUCLEUS; D-ASPARTATE RECEPTORS; MIXED INHIBITOR; PRIMARY AFFERENTS; SUBTYPES; INTERNALIZATION; ACTIVATION; RESPONSES AB Neurotransmitter receptors that inhibit the release of opioid peptides in the spinal cord may play an important role in modulating pain. Serotonin is an important neurotransmitter in bulbospinal descending pathways, and 5-HT1, receptors have been shown to inhibit synaptic transmission. Our goal was to determine whether 5-HT1A receptors inhibit opioid release in the spinal cord. Opioid release was evoked from rat spinal cord slices by electrically stimulating one dorsal horn, and measured in situ through the internalization of mu-opioid receptors in dorsal horn neurons. Stimulation with 1000 square pulses at 500 Hz produced internalization in 60% of the mu-opioid receptor neurons in the stimulated dorsal horn, but not in the contralateral one. The selective 5-HT1A receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) inhibited the evoked mu-opioid receptor internalization by about 50%, with an approximate IC50 of 50 nM. The effect of 8-OH-DPAT was attributed to inhibition of opioid release and not of the receptor internalization process, because 8-OH-DPAT did not inhibit the internalization induced by incubating the slices with a mu-opioid receptor agonist (endomorphin-2, 100 nM). The selective 5-HT1A receptor antagonist WAY100135 (10 mu M) blocked the inhibition produced by 1 mu M 8-OH-DPAT. These results show that 5-HT1A receptors inhibit opioid release in the spinal dorsal horn, probably from a subpopulation of enkephalin-containing presynaptic terminals. Therefore, 5-HT1A receptors likely decrease the analgesia produced by endogenously released opioids. (c) 2007 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci, Los Angeles, CA 90095 USA. Womans Hlth & CURE, Digest Dis Res Ctr, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. RP Marvizon, JCG (reprint author), VA Greater Los Angeles Hlthcare Syst, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu RI Chen, Wenling/A-4490-2012 FU NIDA NIH HHS [R01 DA012609-07, 2 RO1-DA012609, R01 DA012609, R01 DA012609-06A1, R01 DA012609-08] NR 47 TC 17 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 16 PY 2007 VL 1158 BP 57 EP 62 DI 10.1016/j.brainres.2007.05.006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 199QN UT WOS:000248710400006 PM 17555728 ER PT J AU Xiang, ZM Lin, T Reeves, SA AF Xiang, Zhongmin Lin, Tong Reeves, Steven A. TI 15d-PGJ2 induces apoptosis of mouse oligodendrocyte precursor cells SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; PROSTAGLANDIN-D SYNTHASE; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; MULTIPLE-SCLEROSIS; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CYCLOPENTENONE PROSTAGLANDINS; NEURONAL APOPTOSIS; PPAR-GAMMA; KAPPA-B AB Background: Prostaglandin ( PG) production is associated with inflammation, a major feature in multiple sclerosis ( MS) that is characterized by the loss of myelinating oligodendrocytes in the CNS. While PGs have been shown to have relevance in MS, it has not been determined whether PGs have a direct effect on cells within the oligodendrocyte lineage. Methods: Undifferentiated or differentiated mouse oligodendrocyte precursor (mOP) cells were treated with PGE2, PGF2 alpha, PGD2 or 15-deoxy-(Delta 12,14)- PGJ2 (15d-PGJ2). Cell growth and survival following treatment were examined using cytotoxicity assays and apoptosis criteria. The membrane receptors for PGD2 and the nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma, as well as reactive oxygen species (ROS) in the death mechanism were examined. Results: PGE2 and PGF2a had minimal effects on the growth and survival of mOP cells. In contrast, PGD2 and 15d-PGJ2 induced apoptosis of undifferentiated mOP cells at relatively low micromolar concentrations. 15d-PGJ2 was less toxic to differentiated mOP cells. Apoptosis was independent of membrane receptors for PGD2 and the nuclear receptor PPAR gamma. The cytotoxicity of 15d-PGJ2 was associated with the production of ROS and was inversely related to intracellular glutathione (GSH) levels. However, the cytotoxicity of 15d-PGJ2 was not decreased by the free radical scavengers ascorbic acid or alpha-tocopherol. Conclusion: Taken together, these results demonstrated that 15d-PGJ2 is toxic to early stage OP cells, suggesting that 15d-PGJ2 may represent a deleterious factor in the natural remyelination process in MS. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIND,CNS Signaling Lab, Charlestown, MA 02129 USA. RP Reeves, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIND,CNS Signaling Lab, 114 16th St, Charlestown, MA 02129 USA. EM zxiang1@partners.org; tlin6@partners.org; sreeves@partners.org NR 63 TC 20 Z9 21 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD JUL 16 PY 2007 VL 4 AR 18 DI 10.1186/1742-2094-4-18 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 213SG UT WOS:000249686800001 PM 17634127 ER PT J AU Gray, L Churchill, MJ Sterjovski, J Witlox, K Learmont, JC Sullivan, JS Wesselingh, SL Gabuzda, D Cunningham, AL McPhee, DA Gorry, PR AF Gray, Lachlan Churchill, Melissa J. Sterjovski, Jasminka Witlox, Kristie Learmont, Jennifer C. Sullivan, John S. Wesselingh, Steven L. Gabuzda, Dana Cunningham, Anthony L. McPhee, Dale A. Gorry, Paul R. TI Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source SO VIROLOGY JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE-TROPIC HIV-1; CORECEPTOR USAGE; CHEMOKINE RECEPTORS; IN-VIVO; DISEASE PROGRESSION; TYPE-1 EVOLUTION; LONGITUDINAL ANALYSIS; SMALL-MOLECULE; BLOOD AB Background: The Sydney blood bank cohort (SBBC) of long-term survivors consists of multiple individuals infected with attenuated, nef-deleted variants of human immunodeficiency virus type I (HIV-1) acquired from a single source. Long-term prospective studies have demonstrated that the SBBC now comprises slow progressors (SP) as well as long-term nonprogressors (LTNP). Convergent evolution of nef sequences in SBBC SP and LTNP indicates the in vivo pathogenicity of HIV-I in SBBC members is dictated by factors other than nef. To better understand mechanisms underlying the pathogenicity of nef-deleted HIV-I, we examined the phenotype and env sequence diversity of sequentially isolated viruses ( n = 2) from 3 SBBC members. Results: The viruses characterized here were isolated from two SP spanning a three or six year period during progressive HIV-I infection ( subjects D36 and C98, respectively) and from a LTNP spanning a two year period during asymptomatic, nonprogressive infection ( subject C18). Both isolates from D36 were R5X4 phenotype and, compared to control HIV-I strains, replicated to low levels in peripheral blood mononuclear cells ( PBMC). In contrast, both isolates from C98 and C18 were CCR5-restricted. Both viruses isolated from C98 replicated to barely detectable levels in PBMC, whereas both viruses isolated from C18 replicated to low levels, similar to those isolated from D36. Analysis of env by V1V2 and V3 heteroduplex tracking assay, V1V2 length polymorphisms, sequencing and phylogenetic analysis showed distinct intra- and inter- patient env evolution. Conclusion: Independent evolution of env despite convergent evolution of nef may contribute to the in vivo pathogenicity of nef-deleted HIV-I in SBBC members, which may not necessarily be associated with changes in replication capacity or viral coreceptor specificity. C1 Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Monash Univ, Dept Pathol & Immunol, Melbourne, Vic 3004, Australia. Austrian Red Cross Blood Serv, Sydney, NSW, Australia. Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Westmead Millennium Inst, Westmead, NSW, Australia. St Vincents Inst Med Res, Natl Serol Reference Lab, Fitzroy, Vic 3065, Australia. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. EM lachlang@burnet.edu.au; churchil@burnet.edu.au; jasminka@burnet.edu.au; kristiewitlox@hotmail.com; JLearmont@arcbs.redcross.org.au; JSullivan@arcbs.redcross.org.au; stevew@burnet.edu.au; dana_gabuzda@dfci.harvard.edu; tony_cunningham@wmi.usyd.edu.au; dale@nrl.gov.au; gorry@burnet.edu.au RI Cunningham, Tony/B-7011-2013; OI Gray, Lachlan/0000-0002-9894-1049; Sterjovski, Jasminka/0000-0002-2471-3000; Cunningham, Anthony/0000-0002-6744-5667 FU NIAID NIH HHS [AI054207, R21 AI054207]; NINDS NIH HHS [NS37277, R01 NS037277] NR 60 TC 11 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD JUL 16 PY 2007 VL 4 AR 75 DI 10.1186/1743-422X-4-75 PG 12 WC Virology SC Virology GA 198ST UT WOS:000248648500001 PM 17634131 ER PT J AU Spiegel, B Schoenfeld, P Naliboff, B AF Spiegel, B. Schoenfeld, P. Naliboff, B. TI Systematic review: the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID QUALITY-OF-LIFE; CHILDHOOD SEXUAL ABUSE; PSYCHIATRIC-DISORDER; YOUNG ADULTHOOD; HEALTH; DEPRESSION; SYMPTOMS; RISK; STRATEGIES; IDEATION AB Background Chronic abdominal pain syndromes may increase the risk of suicidal behaviour - a feature well described in non-visceral pain syndromes. Aim To perform a systematic review to summarize and interpret published data linking chronic abdominal pain syndromes and suicidal behaviour. Methods We performed a structured search to identify studies pertaining to the following questions: (i) What is the prevalence of suicidal behaviour in patients with chronic abdominal pain syndromes, including bowel syndrome (IBS)? (ii) Is the prevalence of suicidal behaviour in chronic abdominal pain syndromes higher than in matched controls? And (iii) is suicidal behaviour in abdominal pain syndromes simply due to psychiatric co-morbidities? Results Thirty-two relevant titles were identified, of which six manuscripts, describing eight studies, met inclusion criteria. Patients with non-IBS syndromes were 3 - 11 times more likely to demonstrate suicidal behaviour vs. controls, while patients with IBS were two to four times more likely to have suicidal behaviour. Chronic abdominal pain was an independent predictor of suicidal behaviour after adjusting for co-morbid psychiatric conditions. Conclusions Chronic abdominal pain syndromes increase the risk for suicidal behaviours. This relationship may exist independently of co-morbid depression, although additional research is needed to better understand this link. These data indicate that clinicians should survey for suicidal behaviour in chronic abdominal pain patients. C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. VA Ctr Excellence Hlth Sci Res, Ann Arbor, MI USA. RP Schoenfeld, P (reprint author), VAMC 111-D,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM pschoenf@med.umich.edu NR 34 TC 26 Z9 28 U1 8 U2 11 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 JUL 15 PY 2007 VL 26 IS 2 BP 183 EP 193 DI 10.1111/j.1365-2036.2007.03357.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 181ZU UT WOS:000247475700005 PM 17593064 ER PT J AU Cavusoglu, E Eng, C Chopra, V Ruwende, C Yanamadala, S Clark, LT Pinsky, DJ Marmur, JD AF Cavusoglu, Erdal Eng, Calvin Chopra, Vineet Ruwende, Cyril Yanamadala, Sunitha Clark, Luther T. Pinsky, David J. Marmur, Jonathan D. TI Usefulness of the serum complement component C4 as a predictor of stroke in patients with known or suspected coronary artery disease referred for coronary angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; REACTIVE PROTEIN; INDEPENDENT PREDICTOR; RISK; EVENTS; WOMEN; ATHEROSCLEROSIS; ACTIVATION; RECEPTOR-1; COMPLEXES AB The complement system has been implicated in the pathogenesis of atherosclerosis. In addition, complement activation and complement-mediated brain injury have been found in a variety of central nervous system diseases, including stroke. However, there are limited data about the value of complement components for prediction of stroke. Complement C3 and C4 levels, in addition to a variety of established biomarkers, were measured in 389 men with known or suspected coronary artery disease referred for coronary angiography for a variety of indications at a Veterans Affairs Medical Center. Patients were followed prospectively for the development of stroke, which was defined and classified according to criteria of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). All strokes were confirmed with magnetic resonance imaging or computed tomography. For the 97% of patients in whom 24-month follow-up data were available, there were 23 strokes (5.9%). By multivariate Cox proportional hazard analysis, complement C4 was an independent predictor of stroke, with a hazard ratio of 1.57 (95% confidence interval 1.03 to 2.39, p = 0.0358). The 24-month stroke-free survival rate for the patients whose complement C4 levels were equal to or below the median value for the entire cohort was 96.1% compared with 90.1% for patients whose complement C4 levels were above the median value, p = 0.0127 by log rank test). In conclusion, in a cohort of men across a spectrum of risk referred for coronary angiography, a single baseline determination of serum complement C4 level is an-independent predictor of the future development of stroke. (C) 2007 Elsevier Inc. All rights reserved. C1 SUNY Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY USA. Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI USA. RP Cavusoglu, E (reprint author), SUNY Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY USA. EM ecavusoglu@aol.com NR 25 TC 15 Z9 16 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 JUL 15 PY 2007 VL 100 IS 2 BP 164 EP 168 DI 10.1016/j.amjcard.2007.02.075 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 194DN UT WOS:000248324400002 PM 17631062 ER PT J AU Shapiro, MD Nieman, K Nasir, K Nomura, CH Sarwar, A Ferencik, M Abbara, S Hoffman, U Gold, HK Jang, IK Brady, TJ Cury, RC AF Shapiro, Michael D. Nieman, Koen Nasir, Khurram Nomura, Cesar H. Sarwar, Ammar Ferencik, Maros Abbara, Sulmy Hoffman, Udo Gold, Herman K. Jang, Ik-Kyung Brady, Thomas J. Cury, Ricardo C. TI Utility of cardiovascular magnetic resonance to predict left ventricular recovery after primary percutaneous coronary intervention for patients presenting with acute ST-segment elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONTRAST-ENHANCED MRI; MICROVASCULAR OBSTRUCTION; PRIMARY ANGIOPLASTY; IMPROVEMENT; INJURY AB Cardiac magnetic resonance (CMR) has been shown to predict left ventricular (LV) recovery in patients after acute ST-segment elevation myocardial infarction. The purpose of this investigation was to determine the relative values of infarct transmurality and microvascular obstruction (MVO) using delayed enhancement CMR to predict LV recovery. We studied 17 patients (mean age 60 10 years, 14 men) presenting with first acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention who underwent CMR within 6 days after presentation and again at 6 months. In total 680 myocardial segments were evaluated, of which 267 (39%) demonstrated delayed hyperenhancement (DHE) and 116 (18%) demonstrated MVO. Unadjusted odds ratio (OR) for any improvement in regional LV function with increasing DHE category (< 50%, 51% to 75%, > 75% transmurality) was 0.20 (95% confidence interval [CI] 0.13 to 0.30, p < 0.0001), whereas it was 0.40 (95% CO 0.28 to 0.55, p < 0.0001) with increasing MVO category (0, < 50th, > 50th percentile). However, when coadjusted. together, the relation remained robust with regard to degree of transmurality of DHE (OR 0.21, 95% CI 0.13 to 0.36, p < 0.0001), but the relation was lost for MVO (OR 0.90, 95% CI 0.58 to 1.40, p = 0.64). In conclusion, when using the delayed enhancement technique for assessment of DHE and MVO, degree of infarct transmurality appears to be a more powerful predictor of LV recovery by CMR. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Shapiro, MD (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM mdshapiro@partners.org RI Nomura, Cesar/H-1636-2012 FU NHLBI NIH HHS [1T32 HL076136-02] NR 18 TC 15 Z9 15 U1 0 U2 1 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 JUL 15 PY 2007 VL 100 IS 2 BP 211 EP 216 DI 10.1016/j.amjcard.2007.02.079 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 194DN UT WOS:000248324400012 PM 17631072 ER PT J AU Williamson, RE Darrow, KN Michaud, S Jacobs, JS Jones, MC Eberl, DF Maas, RL Liberman, MC Morton, CC AF Williamson, Robin E. Darrow, Keith N. Michaud, Sebastien Jacobs, Julie S. Jones, Marilyn C. Eberl, Daniel F. Maas, Richard L. Liberman, M. Charles Morton, Cynthia C. TI Methylthioadenosine phosphorylase (MTAP) in hearing: Gene disruption by chromosomal rearrangement in a hearing impaired individual and model organism analysis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE deafness; chromosomal translocation; FISH; Drosophila model; mouse model ID RECTIFIER K+ CHANNELS; TOWNES-BROCKS-SYNDROME; SYNDROME TYPE-I; POTASSIUM CHANNEL; ALPHA-DIFLUOROMETHYLORNITHINE; SPERMINE SYNTHASE; STRIA VASCULARIS; MIXED DEAFNESS; DROSOPHILA; MUTATIONS AB Genes with a role in the auditory system have been mapped by genetic linkage analysis of families with heritable deafness and then cloned through positional candidate gene approaches. Another positional method for gene discovery is to ascertain deaf individuals with balanced chromosomal translocations and identify disrupted or disregulated genes at the site(s) of rearrangement. We report herein the use of fluorescence in situ hybridization (FISH) to map the breakpoint regions on each derivative chromosome of a de novo apparently balanced translocation, t(8;9)(q12.1;p21.3)dn, in a deaf individual. Chromosomal breakpoints were assigned initially by GTG-banding of metaphase chromosomes and then BAC probes chosen to map precisely the breakpoints by FISH experiments. To facilitate cloning of the breakpoint sequences, further refinement of the breakpoints was performed by FISH experiments using PCR products and by Southern blot analysis. The chromosome 9 breakpoint disrupts methylthioadenosine phosphorylase (MTAP); no known or predicted genes are present at the chromosome 8 breakpoint. Disruption of MTAP is hypothesized to lead to deafness due to the role of MTAP in metabolizing an inhibitor of polyamine synthesis. Drosophila deficient for the MTAP ortholog, CG4802, were created and their hearing assessed; no hearing loss phenotype was observed. A knockout mouse model for MTAP deficiency was also created and no significant hearing loss was detected in heterozygotes for Mtap. Homozygous Mtap-deficient mice were embryonic lethal. (C) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Med, Div Genet, Boston, MA 02115 USA. Univ Iowa, Dept Biol Sci, Iowa City, IA USA. Univ Calif San Diego, Childrens Hosp, Dept Genet Dysmorphol, San Diego, CA 92103 USA. RP Morton, CC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, NRB 160,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cmorton@partners.org FU NIDCD NIH HHS [F31 DC005712, P30 DC005209, P30 DC5209, R01 DC000188, R01 DC000188-26, R01 DC000188-27, R01 DC004848, R01 DC004848-05, R01 DC004848-06, R01 DC004848-07, R01 DC0188, R01 DC03402, R01 DC04848]; NIGMS NIH HHS [P01 GM061354] NR 43 TC 9 Z9 10 U1 0 U2 2 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 JUL 15 PY 2007 VL 143A IS 14 BP 1630 EP 1639 DI 10.1002/ajmg.a.31724 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 186EB UT WOS:000247760800015 PM 17534888 ER PT J AU Wilens, TE Biederman, J Adamson, J Monuteaux, M Henin, A Sgambati, S Santry, A Faraone, SV AF Wilens, Timothy E. Biederman, Joseph Adamson, Joel Monuteaux, Michael Henin, Aude Sgambati, Stephanie Santry, Alison Faraone, Stephen V. TI Association of bipolar and substance use disorders in parents of adolescents with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adolescents; bipolar disorder; cosegregation; familial; parents; substance abuse ID FAMILIAL TRANSMISSION; EARLY-ONSET; FOLLOW-UP; ALCOHOLISM; ABUSE; AGE; COMORBIDITY; CHILDREN; ILLNESS; MANIA AB Background: We have previously shown that juvenile bipolar disorder (BPD) is a risk for substance use disorders (SUD). Here we examine the expression of both disorders in families of youth with BPD to evaluate the familial risk mechanism. Methods: We studied 108 adolescent BPD probands with 187 parents (34 with SUD and 58 parents) and 96 control probands with 177 parents with structured interviews. We compared the prevalence of BPD and SUD with Cox proportional hazards models with time to onset of BPD or SUD as the dependent variable and proband diagnosis (Control, BPD, or BPD+SUD) as the independent variable. Results: The parents of the proband youth with BPD (without SUD) and BPD+SUD were more likely to develop BPD than the parents of control subjects [omnibus test chi(2) = 10.18, p = .006]; we found no differences between the two bipolar groups. Parents of proband youth with BPD and with BPD+SUD were more likely than relatives of control subjects to develop SUD [omnibus test chi(2) = 14.69, p < .001]; however, we found no differences between the parents of the two proband bipolar groups. Within the parents of proband youth with BPD+SUD, we found higher risk of SUD in parents with BPD than in those without BPD [chi(2) = 8.39, p = .004], although the frequency of BPD was low in this group of parents. Conclusions: Bipolar disorder and SUD are prevalent in the first-degree relatives of adolescents with BPD. Adults with BPD were more likely to manifest SUD with preliminary evidence of BPD and SUD cosegregation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit,Yawkey Ctr Outpatient, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. SUNY Syracuse, Dept Psychiat, Syracuse, NY 13210 USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit,Yawkey Ctr Outpatient, 32 Fruit St,YAW 6A 6900, Boston, MA 02114 USA. EM twilens@partners.org OI Adamson, Joel/0000-0002-1399-5786; Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [R01 DA12945, K24 DA016264, U10 DA15831] NR 45 TC 21 Z9 21 U1 3 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 JUL 15 PY 2007 VL 62 IS 2 BP 129 EP 134 DI 10.1016/j.biopsych.2006.11.022 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189AV UT WOS:000247961700005 PM 17481590 ER PT J AU Marty, FM Bryar, J Browne, SK Schwarzberg, T Ho, VT Bassett, IV Koreth, J Alyea, EP Soiffer, RJ Cutler, CS Antin, JH Baden, LR AF Marty, Francisco M. Bryar, Julie Browne, Sarah K. Schwarzberg, Talya Ho, Vincent T. Bassett, Ingrid V. Koreth, John Alyea, Edwin P. Soiffer, Robert J. Cutler, Corey S. Antin, Joseph H. Baden, Lindsey R. TI Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; RISK-FACTORS; CMV INFECTION; UNRELATED DONORS; PP65 ANTIGENEMIA; INTRAVENOUS GANCICLOVIR; COMPARING METHOTREXATE; MYCOPHENOLATE-MOFETIL; IMMUNE RECONSTITUTION; ORAL VALGANCICLOVIR AB Sirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of cytomegalovirus (CMV) disease. Whether sirolimus has a similar effect on CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is not known. We evaluated 606 patients who underwent HSCT between April 2000 and June 2004 to identify risk factors for CMV reactivation 100 days after transplantation. The cohort included 252 patients who received sirolimus-tacrolimus for graft-versus-host disease (GVHD) prophylaxis; the rest received non-sirolimus-based regimens. An initial positive CMV DNA hybrid capture assay was observed in 225 patients (37.1%) at a median 39 days after HSCT for an incidence rate of 0.50 cases/100 patient-days (95% confidence interval [Cl], 0.44-0.57). Multivariable Cox modeling adjusting for CMV donor-recipient serostatus pairs, incident acute GVHD, as well as other important covariates, confirmed a significant reduction in CMV reactivation associated with sirolimus-tacrolimus-based GVHD prophylaxis, with an adjusted HR of 0.46 (95% CI, 0.27-0-78; P =.004). The adjusted HR was 0.22 (95% Cl, 0.09-0.55; P =.001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR, 0.66; P =.14 and P =.35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org RI ieong, bee/C-5840-2012 FU NHLBI NIH HHS [HL070149, P01 HL070149] NR 58 TC 80 Z9 81 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2007 VL 110 IS 2 BP 490 EP 500 DI 10.1182/blood-2007-01-069294 PG 11 WC Hematology SC Hematology GA 191EH UT WOS:000248112400010 PM 17392502 ER PT J AU Kiziltepe, T Hideshima, T Ishitsuka, K Ocio, EM Raje, N Catley, L Li, CQ Trudel, LJ Yasui, H Vallet, S Kutok, JL Chauhan, D Mitsiades, CS Saavedra, JE Wogan, GN Keefers, LK Shami, PJ Anderson, KC AF Kiziltepe, Tanyel Hideshima, Teru Ishitsuka, Kenji Ocio, Enrique M. Raje, Noopur Catley, Laurence Li, Chun-Qi Trudel, Laura J. Yasui, Hiroshi Vallet, Sonia Kutok, Jeffery L. Chauhan, Dharminder Mitsiades, Constantine S. Saavedra, Joseph E. Wogan, Gerald N. Keefers, Larry K. Shami, Paul J. Anderson, Kenneth C. TI JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells SO BLOOD LA English DT Article ID PROTEASOME INHIBITOR PS-341; HUMAN LYMPHOBLASTOID-CELLS; OVERCOMES DRUG-RESISTANCE; MOLECULAR-MECHANISMS; S-TRANSFERASE; CAM-DR; KINASE; INTERLEUKIN-6; REPAIR; ATM AB Here we investigated the cytotoxicity of JS-K, a prodrug designed to release nitric oxide (NO center dot) following reaction with glutathione S-transferases, in multiple myeloma (MM). JS-K showed significant cytotoxicity in both conventional therapy-sensitive and -resistant MM cell lines, as well as patient-derived MM cells. JS-K induced apoptosis in MM cells, which was associated with PARP, caspase-8, and caspase-9 cleavage; increased Fas/ CD95 expression; Mcl-1 cleavage; and Bcl-2 phosphorylation, as well as cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (EndoG) release. Moreover, JS-K overcame the survival advantages conferred by interieukin-6 (IL-6) and insulin-like growth factor 1 (IGF-1), or by adherence of MM cells to bone marrow stromal cells. Mechanistic studies revealed that JS-K-induced cytotoxicity was mediated via NO center dot in MM cells. Furthermore, JS-K induced DNA doublestrand breaks (DSBs) and activated DNA damage responses, as evidenced by neutral comet assay, as well as H2AX, Chk2 and p53 phosphorylation. JS-K also activated c-Jun NH2-terminal kinase (JNK) in MM cells; conversely, inhibition of JNK markedly decreased JS-K-induced cytotoxicity. Importantly, bortezomib significantly enhanced JS-K-induced cytotoxicity. Finally, JS-K is well tolerated, inhibits tumor growth, and prolongs survival in a human MM xenograft mouse model. Taken together, these data provide the preclinical rationale for the clinical evaluation of JS-K to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. SAIC Frederick, Frederick, MD USA. NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21701 USA. Univ Utah, Div Med Oncol, Salt Lake City, UT USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM tanyel_kiziltepe@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu RI li, Chunqi/D-9650-2011; Catley, Laurence/E-5313-2013 FU Intramural NIH HHS; NCI NIH HHS [N01-CO12400, N01CO12400, P0-1 CA78373, P50 CA100707]; PHS HHS [R0-1 A50947] NR 54 TC 78 Z9 83 U1 1 U2 11 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 JUL 15 PY 2007 VL 110 IS 2 BP 709 EP 718 DI 10.1182/blood-2006-10-052845 PG 10 WC Hematology SC Hematology GA 191EH UT WOS:000248112400034 PM 17384201 ER PT J AU Yamini, B Yu, X Dolan, ME Wu, MH Kufe, DW Weichselbaum, RR AF Yamini, Bakhtiar Yu, Xiaohong Dolan, M. Eileen Wu, Michael H. Kufe, Donald W. Weichselbaum, Ralph R. TI Inhibition of nuclear factor-kappa B activity by temozolomide involves O-6-methylguanine-induced inhibition of p65 DNA binding SO CANCER RESEARCH LA English DT Article ID HUMAN TUMOR-CELLS; MISMATCH REPAIR; ALKYLATING-AGENTS; ANTITUMOR IMIDAZOTETRAZINES; TRANSCRIPTIONAL ACTIVITY; INDUCED TOXICITY; APOPTOSIS; DAMAGE; ALKYLTRANSFERASE; GLIOBLASTOMA AB The alkylating agent temozolomide, commonly used in the treatment of malignant glioma, causes cellular cytotoxicity by forming O-6-methylguanine adducts. In this report, we investigated whether temozolomide alters the activity of the transcription factor nuclear factor-kappa B (NF-kappa B). Temozolomide inhibits basal and tumor necrosis factor alpha (TNF alpha)-induced NF-kappa B transcriptional activity without altering phosphorylation or degradation of inhibitor of kappa B-alpha. Inhibition of NF-kappa B is secondary to attenuation of p65 DNA binding, not nuclear translocation. Inhibition of DNA binding is shown both in vitro, with gel shift studies and DNA binding assays, and in vivo at kappa B sites. Consistent with inhibition of NF-kappa B activity, temozolomide reduces basal and TNF alpha-induced kappa B-dependent gene expression. Temozolomide also inhibits NF-kappa B activated by inducers other than TNF alpha, including lipopolysaccharide, doxorubicin, and phorbol 12-myristate 13-acetate. The inhibitory action of temozolomide on NF-kappa B is observed to be maximal following pretreatment of cells with temozolomide for 16 h and is also seen with the S(N)1-type methylating agent methyinitrosourea. The ability of temozolomide to form O-6-methylguanine adducts is important for inhibition of NF-kappa B as is the presence of a functioning mismatch repair svstem. Activation of NF-kappa B with TNF alpha before administration o f temozolomide reduces the cytotoxicity of temozolomide, whereas 16-h pretreatment with temozolomide resensitizes cells to killing. This work shows a mechanism whereby O-6-methylguanine adducts formed by temozolomide lead to inhibition of NF-kappa B activitv and illustrates a link between mismatch repair processing of alkylator-induced DNA damage and cell death. C1 Univ Chicago, Pritzker Sch Med, Neurosurg Sect, Dept Surg, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Yamini, B (reprint author), Univ Chicago Hosp, Neurosurg Sect, MC 4066,5841 S Maryland Ave, Chicago, IL 60637 USA. EM byamini@surgery.bsd.uchicago.edu FU NCI NIH HHS [R01 CA 81583, R01 CA 111423, P50 CA 097247] NR 50 TC 27 Z9 29 U1 1 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 JUL 15 PY 2007 VL 67 IS 14 BP 6889 EP 6898 DI 10.1158/0008-5472.CAN-06-4496 PG 10 WC Oncology SC Oncology GA 194BN UT WOS:000248319000043 PM 17638900 ER PT J AU Dudzinski, DM Michel, T AF Dudzinski, David M. Michel, Thomas TI Life history of eNOS: Partners and pathways SO CARDIOVASCULAR RESEARCH LA English DT Review DE nitric oxide synthase; post-translational modifications; sub-cellular targeting; protein phosphorylation; protein acylation; S-nitrosylation ID NITRIC-OXIDE SYNTHASE; VASCULAR ENDOTHELIAL-CELLS; AKT-DEPENDENT PHOSPHORYLATION; ESTROGEN-RECEPTOR-ALPHA; PROTEIN-KINASE AKT; S-NITROSYLATION; GROWTH-FACTOR; PLASMALEMMAL-CAVEOLAE; ACTIN CYTOSKELETON; SIGNALING PATHWAYS AB The complex regulation of eNOS (endothelial nitric oxide synthase) in cardiovascular physiology occurs at multiple stages. eNOS mRNA levels are controlled both at the transcriptional and post-transcriptional phases, and epigenetic mechanisms appear to modulate tissue-specific eNOS expression. The eNOS enzyme reversibly associates with a diverse family of protein partners that regulate eNOS sub-cellular localization, catalytic function, and biological activity. eNOS enzyme activity and sub-cellular localization are intimately controlled by post-translational modifications including phosphorylation, nitrosylation, and acylation. The multiple extra-cellular stimuli affecting eNOS function coordinate their efforts through these key modifications to dynamically control eNOS and NO bioactivity in the vessel wall. This review will focus on the biochemical partners and perturbations of the eNOS protein as this vital enzyme undergoes modulation by diverse signal transduction pathways in the vascular endothelium. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Michel, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM tmichel@rics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL046457-17, R01 HL046457, P01 HL048743, P01 HL048743-16]; NIGMS NIH HHS [R01 GM036259-24, R01 GM036259] NR 141 TC 229 Z9 238 U1 1 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUL 15 PY 2007 VL 75 IS 2 BP 247 EP 260 DI 10.1016/j.cardiores.2007.03.023 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 193TA UT WOS:000248296300006 PM 17466957 ER PT J AU Bloch, KD Ichinose, F Roberts, JD Zapol, WM AF Bloch, Kenneth D. Ichinose, Fumito Roberts, Jesse D., Jr. Zapol, Warren M. TI Inhaled NO as a therapeutic agent SO CARDIOVASCULAR RESEARCH LA English DT Review DE pulmonary circulation; nitric oxide ID PERSISTENT PULMONARY-HYPERTENSION; RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; NITRIC-OXIDE INHALATION; ISCHEMIA-REPERFUSION INJURY; VENTRICULAR ASSIST DEVICE; CONGENITAL HEART-DISEASE; PREMATURE-INFANTS; BRONCHOPULMONARY DYSPLASIA; CARDIOVASCULAR-SYSTEM AB In 1991, Frostell and colleagues reported that breathing low concentrations of nitric oxide (NO) decreased pulmonary artery pressure (PAP) in awake lambs with experimental pulmonary hypertension (PH) [Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 1991;83:2038-47]. Subsequently, efforts of multiple research groups studying animals and patients led to approval of inhaled NO by the US Food and Drug Administration in 1999 and the European Medicine Evaluation Agency and European Commission in 2001. Inhaled NO is currently indicated for the treatment of term and near-term neonates with hypoxemia and PH. Since regulatory approval, several studies have suggested that NO inhalation can prevent chronic lung disease in premature infants. In addition, unanticipated systemic effects of inhaled NO may lead to treatments for a variety of disorders including ischemia-reperfusion injury. This review summarizes the pharmacology and physiological effects of breathing NO. The application of inhaled NO to hypoxemic neonates with PH is discussed including recent studies exploring the use of inhaled NO to prevent bronchopulmonary dysplasia in premature infants. This review also highlights the application of inhaled NO to treat adults with cardiopulmonary disease, strategies to augment the efficacy of inhaled NO, and potential applications of the systemic effects of the gas. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Bloch, KD (reprint author), Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Thier 5,55 Fruit St, Boston, MA 02114 USA. EM kdbloch@partners.org FU NHLBI NIH HHS [K08 HL071987, R01 HL042397-17, R01 HL074352-04, R01 HL080316, K08 HL071987-04, R01 HL074352, R01 HL080316-02] NR 87 TC 71 Z9 75 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUL 15 PY 2007 VL 75 IS 2 BP 339 EP 348 DI 10.1016/j.cardiores.2007.04.014 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 193TA UT WOS:000248296300014 PM 17544387 ER PT J AU Williams, GL Roberts, TM Gjoerup, OV AF Williams, Grace L. Roberts, Thomas M. Gjoerup, Ole V. TI Bub1 - Escapades in a cellular world SO CELL CYCLE LA English DT Article DE bub1; mitosis; spindle checkpoint; chromosomal instability; aneuploidy; p53; kinase; SV40 ID SPINDLE-ASSEMBLY CHECKPOINT; TUMOR-PROLIFERATING ACTIVITY; AGING-ASSOCIATED PHENOTYPES; MITOTIC CHECKPOINT; CHROMOSOME SEGREGATION; KINETOCHORE LOCALIZATION; SACCHAROMYCES-CEREVISIAE; INDUCED SENESCENCE; INNER CENTROMERE; DNA-REPLICATION AB The spindle assembly checkpoint is an important surveillance mechanism that ensures high fidelity mitotic chromosome segregation. This is accomplished by monitoring whether sister chromatids lack tension or attachment to spindle microtubules. It is mediated by checkpoint complexes or individual proteins that inhibit the ubiquitin ligase activity of the anaphase-promoting complex/cyclosome (APC/C) via targeting of the Cdc20 regulatory subunit. The Bub1 kinase is a key spindle checkpoint regulatory protein. Bub1 also plays more pleiotropic roles. Thus, Bub1 is required for assembly of a functional inner centromere, sister chromatid cohesion via targeting of the Shugoshin protein, and metaphase congression. Evidence based on Bub1 mutations in colorectal cancers suggests it might be a driving force in tumorigenesis via generation of chromosomal instability (CIN) and aneuploidy. Recently we reported a surveillance mechanism linking loss of Bub1 to activation of the p53 pathway, specifically premature cell senescence in normal human fibroblasts. Interestingly, SV40 large T antigen ( LT) targets Bub1 and this is correlated with oncogenic transformation and compromise of the spindle checkpoint. Future studies on Bub1 combining genetic approaches with analysis of LT perturbations are likely to yield further insight. C1 Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Mol Virol Program, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. Univ Pittsburgh, Inst Canc, Mol Virol Program, Pittsburgh, PA USA. RP Gjoerup, OV (reprint author), Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Mol Virol Program, 5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM ovg27@pitt.edu NR 73 TC 19 Z9 19 U1 1 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 15 PY 2007 VL 6 IS 14 BP 1699 EP 1704 PG 6 WC Cell Biology SC Cell Biology GA 205CR UT WOS:000249091300006 PM 17643075 ER PT J AU Davis, IJ Fisher, DE AF Davis, Ian J. Fisher, David E. TI MiT transcription factor associated malignancies in man SO CELL CYCLE LA English DT Review DE microphthalmia; TFEB; TFE3; TFEC; MYC; MiT family; melanoma; clear cell sarcoma; renal cell carcinoma ID CLEAR-CELL-SARCOMA; LOOP-HELIX PROTEIN; SOFT PART SARCOMA; GENE FUSION; TFE3 GENE; MELANOCYTE DEVELOPMENT; SPLICING FACTOR; CHROMOSOME-TRANSLOCATION; RENAL ADENOCARCINOMA; WAARDENBURG-SYNDROME AB The discovery of recurrent genetic abnormalities in cancer cells has often led to the identification of novel oncogenic genes and gene families. The nature of these alterations may also offer insights into the mechanisms by which these genes mediate their oncogenic role. Amplification, translocation, deletion and point mutation are common mechanisms that result in gain- or loss-of-function of cancer associated genes. Several studies have recently demonstrated multiple genetic strategies that ultimately converge to dysregulate members of the MiT transcription factor family in cancer. The shared dependence on aberrant MiT activity thus defines an expanding family of human solid tumors. C1 Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pediat,Div Hematol, Chapel Hill, NC 27599 USA. Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat Oncol, Melanoma Program Med Oncol, Boston, MA USA. RP Davis, IJ (reprint author), Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pediat,Div Hematol, Chapel Hill, NC 27599 USA. EM ian_davis@med.unc.edu FU NCI NIH HHS [K08 CA100400] NR 93 TC 16 Z9 18 U1 0 U2 7 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 15 PY 2007 VL 6 IS 14 BP 1724 EP 1729 PG 6 WC Cell Biology SC Cell Biology GA 205CR UT WOS:000249091300010 PM 17630504 ER PT J AU Carvalho, LDS Teixeira, LK Carrossini, N Caldeira, ATN Ansel, KM Rao, A Viola, JPB AF Carvalho, Lilian D. S. Teixeira, Leonardo K. Carrossini, Nina Caldeira, Anita T. N. Ansel, K. Mark Rao, Anjana Viola, Joao P. B. TI The NFAT1 transcription factor is a repressor of cyclin A2 gene expression SO CELL CYCLE LA English DT Article DE cyclin; gene expression; lymphocytes; NFAT; transcription factor ID CELL-CYCLE; REGULATED TRANSCRIPTION; RESPONSIVE ELEMENT; DOWN-REGULATION; MURINE CYCLIN; GROWTH-FACTOR; MICE LACKING; T-CELLS; CALCINEURIN; PROMOTER AB The NFAT (Nuclear Factor of Activated T cells) family of transcription factors plays a central role in the regulation of several genes related to the immune response. Recently, NFAT proteins have been implicated in the proliferation and differentiation of different cell types. Previous studies have shown that NFAT1-deficient mice display lymphocyte hyperproliferation, shortened cell cycle duration, and cyclin overexpression. Here, we demonstrate that cyclin A2 expression is upregulated in the absence of NFAT1 in lymphocytes. Ectopic expression of NFAT1 in CHO cells decreases cyclin A2 levels. Indeed, NFAT1 binds to a consensus binding site found at the mouse cyclin A2 promoter in vitro and in vivo. Luciferase reporter assays show that NFAT1 downregulates cyclin A2 expression by directly binding to the cyclin A2 promoter. Together, these results indicate that the NFAT1 transcription factor represses cyclin A2 expression in lymphocytes, and may act as a silencer of gene transcription during the cell cycle. C1 Inst Nacl Canc, Div Biol Celular, BR-20231 Rio De Janeiro, Brazil. Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA USA. RP Viola, JPB (reprint author), Inst Nacl Canc, Div Biol Celular, Rua Andre Cavalcanti 37, BR-20231 Rio De Janeiro, Brazil. EM jpviola@inca.gov.br RI Teixeira, Leonardo Karam/S-8773-2016; OI Teixeira, Leonardo Karam/0000-0001-6117-423X; Viola, Joao/0000-0002-0698-3146 FU FIC NIH HHS [R03-TW006466-01] NR 47 TC 35 Z9 36 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 15 PY 2007 VL 6 IS 14 BP 1789 EP 1795 PG 7 WC Cell Biology SC Cell Biology GA 205CR UT WOS:000249091300018 PM 17637565 ER PT J AU Musher, DM Rueda, AM Kaka, AS Mapara, SM AF Musher, Daniel M. Rueda, Adriana M. Kaka, Anjum S. Mapara, Sulaiman M. TI The association between pneumococcal pneumonia and acute cardiac events SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; HEAVY PHYSICAL EXERTION; CRITICALLY-ILL PATIENTS; CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; NATRIURETIC PEPTIDE; SEPTIC SHOCK; TROPONIN-I AB Background. Increased cardiac stress, hypoxemia, and inflammation may contribute to acute cardiac events, such as myocardial infarction ( MI), arrhythmia, and/or congestive heart failure ( CHF). We sought to determine the incidence of such events in patients who were hospitalized for community-acquired pneumococcal pneumonia. Methods. We studied the medical records of all patients who were admitted for pneumococcal pneumonia during a 5-year period ( 2001-2005) to identify those who had MI, atrial fibrillation or ventricular tachycardia, or new-onset or worsening CHF at the time of hospital admission. Results. Of 170 patients, 33 ( 19.4%) had >= 1 of these major cardiac events. Twelve had MI, of whom 2 also had arrhythmia and 5 had new-onset or worsening CHF. Eight had new-onset atrial fibrillation or ventricular tachycardia; 6 of these also had new CHF. Thirteen had newly diagnosed or worsening CHF, without MI or new arrhythmias. Hypoxemia and anemia were prominent. Importantly, patients with concurrent pneumococcal pneumonia and cardiac events had a significantly higher mortality than those with pneumococcal pneumonia alone (P < .008). The coexistence of pulmonary and cardiac disease was often overlooked by admitting physicians who, seeking a unifying diagnosis, emphasized one diagnosis to the exclusion of the other. Conclusions. Patients with pneumococcal pneumonia are at substantial risk for a concurrent acute cardiac event, such as MI, serious arrhythmia, or new or worsening CHF. This concurrence significantly increases mortality due to pneumonia. Admitting physicians tend to seek a unifying diagnosis, but the frequent coexistence of pneumonia and cardiac events indicates the importance of considering multiple diagnoses. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Care Line, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Care Line, Rm 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM daniel.musher@med.va.gov FU NIAID NIH HHS [5T32AI055413-03] NR 43 TC 102 Z9 112 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2007 VL 45 IS 2 BP 158 EP 165 DI 10.1086/518849 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 180EC UT WOS:000247343900003 PM 17578773 ER PT J AU Ingber, DE Levin, M AF Ingber, Donald E. Levin, Michael TI What lies at the interface of regenerative medicine and developmental biology? SO DEVELOPMENT LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; SUSTAINED DEPOLARIZATION; CYTOSKELETAL TENSION; INDUCTION; MORPHOGENESIS; SPECIFICATION; NEURONS; PATHWAY; SYSTEM; SHAPE C1 Childrens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Harvard Med Sch, Dept Surg, Boston, MA 02115 USA. Harvard Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, Dept Dev Biol, Boston, MA 02115 USA. RP Ingber, DE (reprint author), Childrens Hosp, Harvard Med Sch, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. EM donald.ingber@childrens.harvard.edu NR 45 TC 52 Z9 53 U1 0 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL 15 PY 2007 VL 134 IS 14 BP 2541 EP 2547 DI 10.1242/dev.003707 PG 7 WC Developmental Biology SC Developmental Biology GA 194RH UT WOS:000248361000001 PM 17553905 ER PT J AU Roberts, S Calautti, E Vanderweil, S Nguyen, HO Foley, A Baden, HP Viel, A AF Roberts, S. Calautti, E. Vanderweil, S. Nguyen, H. O. Foley, A. Baden, H. P. Viel, A. TI Changes in localization of human discs large (hDlg) during keratinocyte differentiation is associated with expression of alternatively spliced hDlg variants SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE hDlg; discs large; hDlg splice variants; I2; I3; MAGUK; keratinocyte; squamous epithelium; epithelial differentiation; epithelial proliferation ID LARGE TUMOR-SUPPRESSOR; PROTEASOME-MEDIATED DEGRADATION; HUMAN HOMOLOG; EPITHELIAL-CELLS; DROSOPHILA; PROTEIN; MEMBRANE; KINASE; GENE; PROGRESSION AB Alternative spliced variants of the human discs large (hDlg) tumour suppressor are characterized by combinations of insertions. Here, using insertions 12- and 13-specific antibodies, we show that 12 and 13 variants have distinct distributions in epidermal and cervical epithelia. In skin and cervix, 13 variants are found in the cytoplasm. Cytoplasmic localization of 13 variants decreases as cervical keratinocytes differentiate, concomitant with relocalization to the cell periphery. 12 variants are found at the cell periphery of differentiated epidermal and cervical keratinocytes. Nuclear localization of 12 variants was evident in both tissues, with concentration of nuclear 12 variants in basal and parabasal cervical keratinocytes. A prominent nuclear localization of hDlg in cells of hyperproliferative layers of psoriatic lesions, but not in mature differentiated keratinocytes, together with 12 redistribution in differentiating keratinocytes, suggests that nuclear hDlg functions may be pertinent to growth of undifferentiated cells. Supporting our findings in squamous tissues, a decrease of nuclear hDlg and an increase of membrane-bound and cytoplasmic hDIg upon calcium-induced keratinocyte differentiation were not concomitant processes. Furthermore, we confirm that the exit of 12 variants from the nucleus is linked to stimulation of epithelial differentiation. The dynamic redistribution of hDIg also correlated with a marked increase in the expression of 13 variants while the level of 12 variants showed only a moderate decrease. Because changes in the intracellular distribution of hDIg splice variants, and in their expression levels, correlate with changes in differentiation state we hypothesize that the different hDIg isoforms play distinct roles at various stages of epithelial differentiation. C1 Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham B15 2TT, W Midlands, England. Univ Turin, Mol Biotechnol Ctr, I-10126 Turin, Italy. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Roberts, S (reprint author), Univ Birmingham, Canc Res UK Inst Canc Studies, Vincent Dr, Birmingham B15 2TT, W Midlands, England. EM s.roberts@bham.ac.uk RI Roberts, Sally/N-6143-2014; OI Roberts, Sally/0000-0003-4653-9442; CALAUTTI, Vincenzo/0000-0002-4439-9709 NR 41 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 15 PY 2007 VL 313 IS 12 BP 2521 EP 2530 DI 10.1016/j.yexcr.2007.05.017 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 191EG UT WOS:000248112300001 PM 17574238 ER PT J AU Lynch, RD Francis, SA McCarthy, KM Casas, E Thiele, C Schneeberger, EE AF Lynch, Robert D. Francis, Stacy A. McCarthy, Karin M. Casas, Elizabeth Thiele, Christoph Schneeberger, Eveline E. TI Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE tight junctions; occludin; claudins; cholesterol; detergent-resistant microdomains ID LIPID RAFTS; CELL CHOLESTEROL; MEMBRANE RAFTS; MDCK CELLS; EPITHELIAL-CELLS; PLASMA-MEMBRANE; FATTY-ACID; DOMAINS; COMPLEX; MODULATION AB Differential centrifugation of Triton X-100 or CHAPS lysates from control and cholesterol (CH)-depleted MDCK II cells, segregated integral tight junction (TJ) proteins associated with detergent-resistant membranes (DRMs) into two groups. Group A proteins (occludin, claudin-2 and -3) were detected in large, intermediate and small aggregates in both detergents, whereas group B proteins (claudin-1, -4 and -7) were observed in small aggregates in TX-100 and in intermediate and small aggregates in CHAPS. Depletion of CH altered the distribution of group A and B proteins among the three size categories in a detergent- specific manner. In lysates produced with octyl glucoside, a detergent that selectively extracts proteins from DRMs, group A proteins were undetectable in large aggregates and CH depletion did not alter the distribution of either group A or B proteins in intermediate or small aggregates Neither occludin (group A) nor claudin-1 (group B) was in intimate enough contact with CH to be cross-linked to [H-3]-photo-cholesterol. However, antibodies to either TJ protein co-immunoprecipitated caveolin-1, a CH-binding protein. Unlike claudins, occludin's presence in TJs and DRMs did not require palmitoylation. Equilibrium density centrifugation on discontinuous OptiPrep gradients revealed detergent-related differences in the densities of TJ-bearing DRMs. There was little or no change in those densities after CH depletion. Removing CH from the plasma membrane increased tyrosine and threonine phosphorylation of occludin, and transepithelial electrical resistance (TER) within 30 min. After 2 h of CH efflux, phospho-occludin levels and TER fell below control values. We conclude that the association of integral TJ proteins with DRMS, pelleted at low speeds, is partially CH-depenclent. However, the buoyant density of TJ-associated DRMs is a function of the detergent used and is insensitive to decreases in CH. Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. Univ Massachusetts, Lowell, MA 01854 USA. Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, 149 13th St, Charlestown, MA 02129 USA. EM eschneeberger@partners.org FU NHLBI NIH HHS [R01 HL025822-25A2, HL25822, HL36781, R01 HL025822, R01 HL036781, R01 HL036781-20] NR 43 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 15 PY 2007 VL 313 IS 12 BP 2597 EP 2610 DI 10.1016/j.yexcr.2007.05.009 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 191EG UT WOS:000248112300007 PM 17574235 ER PT J AU Chaiswing, L Bourdeau-Heller, JM Zhong, WX Oberley, TD AF Chaiswing, Luksana Bourdeau-Heller, Jeanne M. Zhong, Weixiong Oberley, Terry D. TI Characterization of redox state of two human prostate carcinoma cell lines with different degrees of aggressiveness SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE cell growth; LNCaP; PC3; redox state; free radicals ID MANGANESE SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; CANCER-CELLS; ANTIOXIDANT ENZYMES; SIGNAL-TRANSDUCTION; NITRIC-OXIDE; TUMOR-GROWTH; STEM-CELLS; IN-VIVO AB We characterized the redox profiles in two different human prostate carcinoma cell lines (LNCaP vs PC3) that are known to exhibit varying degrees of invasiveness/metastatic ability. We confirmed that PC3 cells were more in-vasive than LNCaP cells through an in vitro analysis. The present study documented higher 8-hydroxy-2'-deoxyguanosine levels in PC3 cells than in LNCaP cells. The levels of lipid peroxidation were higher in LNCaP cells than in PC3 cells. The reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio increased to a greater extent during cell growth in PC3 cells than in LNCaP cells, whereas both reduced GSH and GSSG levels were higher in the medium of PC3 cells than in that of LNCaP cells. The levels of reactive oxygen (ROS) and reactive nitrogen species (RNS), both intracellularly and in the medium, were higher for LNCaP cells than for PC3 cells during cell growth. In addition, our results demonstrated higher ROS/RNS levels in LNCaP cells than in PC3 cells in S and G2/M phases of the cell cycle during logarithmic growth. Each cell type showed distinct cytotoxic responses to low-molecular-weight redox-modulating compounds. Our results document that human prostate cancer cell lines of varying degrees of aggressive behavior have distinct redox properties, findings that could lead to novel therapeutic interventions. Published by Elsevier Inc. C1 William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu NR 42 TC 38 Z9 38 U1 0 U2 1 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 JUL 15 PY 2007 VL 43 IS 2 BP 202 EP 215 DI 10.1016/j.freeradbiomed.2007.03.031 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 189TW UT WOS:000248012400007 PM 17603930 ER PT J AU Sicinski, P Zacharek, S Kim, C AF Sicinski, Peter Zacharek, Sima Kim, Carla TI Duality of p27(Kip1) function in tumorigenesis SO GENES & DEVELOPMENT LA English DT Article ID DEPENDENT KINASE INHIBITORS; PROGENITOR-CELL PROLIFERATION; CDK INHIBITOR; HEMATOPOIETIC STEM; MICE LACKING; CYCLE ARREST; LUNG STEM; DIFFERENTIATION; CANCER; P27 C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kim, C (reprint author), Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM Carla.kim@childrens.harvard.edu NR 32 TC 39 Z9 40 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 2007 VL 21 IS 14 BP 1703 EP 1706 DI 10.1101/gad.1583207 PG 4 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 190SE UT WOS:000248078600001 PM 17639075 ER PT J AU Shun, MC Raghavendra, NK Vandegraaff, N Daigle, JE Hughes, S Kellam, P Cherepanov, P Engelman, A AF Shun, Ming-Chieh Raghavendra, Nidhanapati K. Vandegraaff, Nick Daigle, Janet E. Hughes, Siobhan Kellam, Paul Cherepanov, Peter Engelman, Alan TI LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration SO GENES & DEVELOPMENT LA English DT Article DE integrase; LEDGF/p75; HIV-1; AIDS; transcription; integration ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTIONAL COACTIVATOR P75; RETROVIRAL DNA INTEGRATION; HUMAN-CELLS; HUMAN GENOME; IN-VITRO; TYPE-1; PROTEIN; CHROMATIN; SITES AB LEDGF/p75 directly interacts with lentiviral integrase proteins and can modulate their enzymatic activities and chromosomal association. A novel genetic knockout model was established that allowed us for the first time to analyze HIV-1 integration in the absence of LEDGF/p75 protein. Supporting a crucial role for the cofactor in viral replication, HIV-1 vector integration and reporter gene expression were significantly reduced in LEDGF-null cells. Yet, integrase processed the viral cDNA termini normally and maintained its local target DNA sequence preference during integration. Preintegration complexes extracted from knockout cells moreover supported normal levels of DNA strand transfer activity in vitro. In contrast, HIV-1 lost its strong bias toward integrating into transcription units, displaying instead increased affinity for promoter regions and CpG islands. Our results reveal LEDGF/p75 as a critical targeting factor, commandeering lentiviruses from promoter- and/or CpG island-proximal pathways that are favored by other members of Retroviridae. Akin to yeast retrotransposons, disrupting the lentiviral targeting mechanism significantly perturbs overall integration. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Div AIDS, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Imperial Coll London, Div Med, London W2 1PG, England. UCL, Dept Infect, London W1T 4JF, England. RP Cherepanov, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Div AIDS, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM p.cherepanov@imperial.ac.uk; alan_engelman@dfci.harvard.edu RI Cherepanov, Peter/F-6859-2010 OI Cherepanov, Peter/0000-0002-0634-538X FU Medical Research Council [G0600009]; NIAID NIH HHS [AI39394, R01 AI039394, R37 AI039394] NR 60 TC 259 Z9 265 U1 1 U2 9 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 JUL 15 PY 2007 VL 21 IS 14 BP 1767 EP 1778 DI 10.1101/gad.1565107 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 190SE UT WOS:000248078600009 PM 17639082 ER PT J AU Kaneko, S Rozenblatt-Rosen, O Meyerson, M Manley, JL AF Kaneko, Syuzo Rozenblatt-Rosen, Orit Meyerson, Matthew Manley, James L. TI The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3 ' processing and transcription termination SO GENES & DEVELOPMENT LA English DT Article DE RNA polymerase II; pre-mRNA 3 ' processing; XRN2; p54nrb/NonO; PSF ID SPLICING FACTOR PSF; 3' END FORMATION; POLYMERASE-II; SACCHAROMYCES-CEREVISIAE; NUCLEAR-PROTEIN; POLY(A) SIGNAL; PAF1 COMPLEX; GLOBIN GENE; IN-VITRO; HNRNP-L AB Termination of RNA polymerase II transcription frequently requires a poly( A) signal and cleavage/polyadenylation factors. Recent work has shown that degradation of the downstream cleaved RNA by the exonuclease XRN2 promotes termination, but how XRN2 functions with 3'-processing factors to elicit termination remains unclear. Here we show that XRN2 physically associates with 3'-processing factors and accumulates at the 3' end of a transcribed gene. In vitro 3'-processing assays show that XRN2 is necessary to degrade the downstream RNA, but is not required for 3' cleavage. Significantly, degradation of the 3'-cleaved RNA was stimulated when coupled to cleavage. Unexpectedly, while investigating how XRN2 is recruited to the 3'-processing machinery, we found that XRN2 associates with p54nrb/NonO(p54)-protein-associated splicing factor (PSF), multifunctional proteins involved in several nuclear processes. Strikingly, p54 is also required for degradation of the 3'-cleaved RNA in vitro. p54 is present along the length of genes, and small interfering RNA (siRNA)-mediated knockdown leads to defects in XRN2 recruitment and termination. Together, our data indicate that p54nrb/PSF functions in recruitment of XRN2 to facilitate pre-mRNA 3' processing and transcription termination. C1 Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Manley, JL (reprint author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. EM jlm2@columbia.edu RI Meyerson, Matthew/E-7123-2012 FU NIGMS NIH HHS [GM28983, R01 GM028983] NR 59 TC 109 Z9 110 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 2007 VL 21 IS 14 BP 1779 EP 1789 DI 10.1101/gad.1565207 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 190SE UT WOS:000248078600010 PM 17639083 ER PT J AU Yang, SY Li, YP AF Yang, Shuying Li, Yi-Ping TI RGS10-null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+](i) oscillation regulation SO GENES & DEVELOPMENT LA English DT Article DE RGS10; osteopetrosis; [Ca2+](i) oscillation; osteoclast differentiation; RANKL signaling pathway; therapeutic target ID SIGNALING RGS PROTEINS; TRANSCRIPTION FACTOR; IN-VITRO; MICE; BONE; CA2+/CALMODULIN; OSTEOPETROSIS; ACTIVATION; GENE; CALCINEURIN AB Increased osteoclastic resorption leads to many bone diseases, including osteoporosis and rheumatoid arthritis. While rapid progress has been made in characterizing osteoclast differentiation signaling pathways, how receptor activator of nuclear factor kappa B (NF-kappa B) ligand (RANKL) evokes essential [Ca2+](i) oscillation signaling remains unknown. Here, we characterized RANKL-induced signaling proteins and found regulator of G-protein signaling 10 (RGS10) is predominantly expressed in osteoclasts. We generated RGS10-deficient (RGS10(-/-)) mice that exhibited severe osteopetrosis and impaired osteoclast differentiation. Our data demonstrated that ectopic expression of RGS10 dramatically increased the sensitivity of osteoclast differentiation to RANKL signaling; the deficiency of RGS10 resulted in the absence of [Ca2+](i) oscillations and loss of NFATc1; ectopic NFATc1 expression rescues impaired osteoclast differentiation from deletion of RGS10; phosphatidylinositol 3,4,5-trisphosphate (PIP3) is essential to PLC gamma activation; and RGS10 competitively interacts with Ca2+/calmodulin and PIP3 in a [Ca2+](i)-dependent manner to mediate PLC gamma activation and [Ca2+](i) oscillations. Our results revealed a mechanism through which RGS10 specifically regulates the RANKL-evoked RGS10/calmodulin-[Ca2+](i) oscillation-calcineurin-NFATc1 signaling pathway in osteoclast differentiation using an in vivo model. RGS10 provides a potential therapeutic target for the treatment of bone diseases. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM ypli@forsyth.org RI Yang, Shuying/G-4599-2011 FU NIA NIH HHS [R01 AG048388]; NIAMS NIH HHS [AR-44741, AR-48133, R01 AR044741, R01 AR048133, R01 AR066101, R03 AR061052]; NICHD NIH HHS [P30 HD 18655, P30 HD018655]; NIDCR NIH HHS [DE016857, R03 DE016857] NR 44 TC 75 Z9 76 U1 2 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 2007 VL 21 IS 14 BP 1803 EP 1816 DI 10.1101/gad.1544107 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 190SE UT WOS:000248078600012 PM 17626792 ER PT J AU Liu, AK Marcus, KJ Fischl, B Grant, PE Poussaint, TY Rivkin, MJ Davis, P Tarbell, NJ Yock, TI AF Liu, Arthur K. Marcus, Karen J. Fischl, Bruce Grant, P. Ellen Poussaint, Tina Young Rivkin, Michael J. Davis, Peter Tarbell, Nancy J. Yock, Torunn I. TI Changes in cerebral cortex of children treated for medulloblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol DE medulloblastoma; cortical thickness; magnetic resonance imaging ID WHITE-MATTER VOLUME; DOSE CRANIOSPINAL IRRADIATION; SURFACE-BASED ANALYSIS; LONG-TERM SURVIVORS; CHILDHOOD MEDULLOBLASTOMA; NEUROCOGNITIVE DEFICITS; PEDIATRIC-PATIENTS; NEUROPSYCHOLOGICAL SEQUELAE; RADIATION-DOSIMETRY; CORTICAL THICKNESS AB Purpose: Children with medulloblastoma undergo surgery, radiotherapy, and chemotherapy. After treatment, these children have numerous structural abnormalities. Using high-resolution magnetic resonance imaging, we measured the thickness of the cerebral cortex in a group of medulloblastoma patients and a group of normally developing children. Methods and Materials: We obtained magnetic resonance imaging scans and measured the cortical thickness in 9 children after treat of medulloblastoma. The measurements from these children were compared with the measurements from age- and gender-matched normally developing children previously scanned. For additional comparison, the pattern of thickness change was compared with the cortical thickness maps from a larger group of 65 normally developing children. Results: In the left hemisphere, relatively thinner cortex was found in the perirolandic region and the parietooccipital lobe. In the right hemisphere, relatively thinner cortex was found in the parietal lobe, posterior superior temporal gyrus, and lateral temporal lobe. These regions of cortical thinning overlapped with the regions of cortex that undergo normal age-related thinning. Conclusion: The spatial distribution of cortical thinning suggested that the areas of cortex that are undergoing development are more sensitive to the effects of treatment of medulloblastoma. Such quantitative methods may improve our understanding of the biologic effects that treatment has on the cerebral development and their neuropsychological implications. (C) 2007 Elsevier Inc. C1 Harvard Univ, Radiat Oncol Program, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. MIT, Div Hlth Sci & Technol, Dept Comp Sci, Cambridge, MA USA. MIT, Div Hlth Sci & Technol, Artificial Intelligence Lab, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Liu, AK (reprint author), Harvard Univ, Radiat Oncol Program, Sch Med, 375 Longwood Ave, Boston, MA 02115 USA. EM aliu1@partners.org FU NCI NIH HHS [5 P01 CA 21239-26]; NCRR NIH HHS [U24 RR 021382, R01 RR 16594-01A1, P41 RR 14075]; NIBIB NIH HHS [R01 EB 001550]; NICHD NIH HHS [N01 HD 023343]; NIMH NIH HHS [N01 MH 90002]; NINDS NIH HHS [N01 NS 92314, N01 NS 92317, N01 NS 92320, N01 NS 92315, N01 NS 92316, N01 NS 92319] NR 50 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2007 VL 68 IS 4 BP 992 EP 998 DI 10.1016/j.ijrobp.2007.01.034 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 185ZU UT WOS:000247749700006 PM 17379433 ER PT J AU Chambers, MS Posner, M Jones, CU Biel, MA Hodge, KM Vitti, R Armstrong, I Yen, C Weber, RS AF Chambers, Mark S. Posner, Marshall Jones, Christopher Uwe Biel, Merrill A. Hodge, Kenneth M. Vitti, Robert Armstrong, Ingrid Yen, Cindy Weber, Randal S. TI Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE cevimeline; postirradiation xerostomia; head-and-neck cancer; dry mouth; saliva ID INDUCED SALIVARY DYSFUNCTION; QUALITY-OF-LIFE; RADIOTHERAPY; PILOCARPINE; SNI-2011; COMPLICATIONS; IRRADIATION; PREVENTION; GLANDS; RATS AB Purpose: To study the efficacy and safety of cevimeline in two double-blind trials (Studies 003 and 004) enrolling patients with head and neck cancer in whom xerostomia developed after radiotherapy. Methods and Materials: Subjects were randomly assigned to receive cevimeline, 30 mg three times daily, or placebo for 12 weeks, with the possibility of dose escalation to 45 mg three times daily at 6 weeks. The primary efficacy endpoint was the patient's final global evaluation of oral dryness; change in unstimulated salivary flow was a secondary endpoint. Results: Five hundred seventy subjects (284 in Study 003 and 286 in Study 004) were randomized. Significantly more cevimeline-treated subjects than placebo recipients (47.4 % vs. 33.3 %, p = 0.0162) in Study 003 reported improvement in dry mouth in the final global evaluation of oral dryness. No significant difference between groups in the final global evaluation was seen in Study 004, in which a high placebo response rate of 47.6% was observed. In both studies, cevimeline-treated subjects bad significantly greater increases in the objective measure of unstimulated salivary flow than placebo recipients (p = 0.0093 (Study 003] and p = 0.0215 [Study 0041), whereas no significant differences in stimulated salivary flow were observed. The most frequent adverse event was increased sweating. Conclusion: Cevimeline was well tolerated by patients with xerostomia after radiotherapy for head and neck cancer, and oral administration of 30-45 mg of cevimeline three times daily increased unstimulated salivary flow. (C) 2007 Elsevier Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Harvard Univ, Dana Farber Canc Ctr, Boston, MA USA. Radiol Assoc, Sacramento, CA USA. Ear Nose & Throat Specialty Care Minnesota, Minneapolis, MN USA. Commonwlth Ear Nose & Throat, Louisville, KY USA. Daiichi Pharmaceut Co Ltd, Montvale, NJ USA. RP Chambers, MS (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM mchamber@mdanderson.org NR 24 TC 30 Z9 31 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 JUL 15 PY 2007 VL 68 IS 4 BP 1102 EP 1109 DI 10.1016/j.ijrobp.2007.01.019 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 185ZU UT WOS:000247749700022 PM 17379432 ER PT J AU Izawa, A Yamaura, K Albin, MJ Jurewicz, M Tanaka, K Clarkson, MR Ueno, T Habicht, A Freeman, GJ Yagita, H Abdi, R Pearson, T Greiner, DL Sayegh, MH Najafian, N AF Izawa, Atsushi Yamaura, Kazuhiro Albin, Monica J. Jurewicz, Mollie Tanaka, Katsunori Clarkson, Michael R. Ueno, Takuya Habicht, Antje Freeman, Gordon J. Yagita, Hideo Abdi, Reza Pearson, Todd Greiner, Dale L. Sayegh, Mohamed H. Najafian, Nader TI A novel alloantigen-specific CD8(+)PD1(+) regulatory T cell induced by ICOS-B7h blockade in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHRONIC ALLOGRAFT-REJECTION; DEATH-1 PD-1 PATHWAY; COSTIMULATORY PATHWAYS; TOLEROGENIC APC; IMMUNE-RESPONSES; CUTTING EDGE; TOLERANCE; ANTIGEN; MODEL AB Delayed ICOS-B7h signal blockade promotes significant prolongation of cardiac allograft survival in wild-type but not in CD8-deficient C57BL/6 recipients of fully MHC-mismatched BALB/c heart allografts, suggesting the possible generation of CD8(+) regulatory T cells in vivo. We now show that the administration of a blocking anti-ICOS mAb results in the generation of regulatory CD8(+) T cells. These cells can transfer protection and prolong the survival of donor-specific BALB/c, but not third party C3H, heart grafts in CD8-deficient C57BL/6 recipients. This is unique to ICOS-B7h blockade, because B7 blockade by CTLA4-Ig prolongs graft survival in CD8-deficient: mice and does not result in the generation of regulatory CD8(+) T cells. Those cells localize to the graft, produce both IFN-gamma and IL-4 after allostimulation in vitro, prohibit the expansion of alloreactive CD4(+) T cells, and appear to mediate a Th2 switch of recipient CD4(+) T cells after adoptive transfer in vivo. Finally, these cells are not confined to the CD28-negative population but express programmed death 1, a molecule required for their regulatory function in vivo. CD8(+)PD1(+) T cells suppress alloreactive CD4(+) T cells but do not inhibit the functions by alloreactive CD8+ T cells in vitro. These results describe a novel allospecific regulatory CD8(+) PD1(+) T cell induced by ICOS-B7h blockade in vivo. C1 Brigham & Womens Hosp, Childrens Hosp, Harvard Med Sch, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Transplantat Res Ctr, EBRC, 221 Longwood Ave,Third Floor, Boston, MA 02115 USA. EM msayegh@rics.bwh.harvard.edu FU NIAID NIH HHS [P01 AI041521, P01 AI56299, R01 AI51559] NR 44 TC 27 Z9 28 U1 1 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 JUL 15 PY 2007 VL 179 IS 2 BP 786 EP 796 PG 11 WC Immunology SC Immunology GA 186AS UT WOS:000247752100013 PM 17617568 ER PT J AU Serwold, T Hochedlinger, K Inlay, MA Jaenisch, R Weissman, IL AF Serwold, Thomas Hochedlinger, Konrad Inlay, Matthew A. Jaenisch, Rudolf Weissman, Irving L. TI Early TCR expression and aberrant T cell development in mice with endogenous prerearranged T cell receptor genes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE BONE-MARROW; ALPHA-BETA; LINEAGE COMMITMENT; TRANSGENIC MICE; CLONED MICE; THYMOCYTE DEVELOPMENT; NUCLEAR TRANSFER; STEM-CELLS; PROGENITORS; SELECTION AB The factors that regulate the rate of production of T cells by the thymus remain incompletely defined. To test whether generation of functional T cell receptors limits the rate of thymic T cell export, we made use of a line of mice, LN3 alpha beta, that have endogenously prerearranged TCR genes. The prerearranged TCR genes were expressed abnormally early in hemopoietic development, indicating that RAG-mediated recombination, rather than transcription factor expression, is the key determinant of the initiation of robust TCR transcription. Thymic T cell export rates were similar between wild-type (wt) and LN3 alpha beta mice, indicating that T cell maturation rates in these mice are determined by factors other than TCR gene rearrangement. In competitive bone marrow chimeras, however, LN3 alpha beta thymocytes were out-competed by wt cells and failed to develop beyond the double-negative 4 stage. Furthermore, wt progenitors transplanted intrathymically into LN3 alpha beta mice proliferated excessively, suggesting that increased proliferative signals in the LN3 alpha beta thymus compensate for faulty T cell development driven by early TCR expression. C1 Stanford Univ, Dept Pathol, Beckman Ctr, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. RP Serwold, T (reprint author), Stanford Univ, Dept Pathol, Beckman Ctr, B259, Stanford, CA 94305 USA. EM tserwold@staiiford.edu; irv@stanford.edu FU NCI NIH HHS [T32 CA009151, R37-CA84198, R01-CA87869]; NIAID NIH HHS [1F 32 AI 58521, T32 AI007290, R01-AI047457, R01-AI047458]; NICHD NIH HHS [R01-HD0445022] NR 43 TC 30 Z9 31 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 JUL 15 PY 2007 VL 179 IS 2 BP 928 EP 938 PG 11 WC Immunology SC Immunology GA 186AS UT WOS:000247752100029 PM 17617584 ER PT J AU Gulick, RM Su, ZH Flexner, C Hughes, MD Skolnik, PR Wilkin, TJ Gross, R Krambrink, A Coakley, E Greaves, WL Zolopa, A Reichman, R Godfrey, C Hirsch, M Kuritzkes, DR AF Gulick, Roy M. Su, Zhaohui Flexner, Charles Hughes, Michael D. Skolnik, Paul R. Wilkin, Timothy J. Gross, Robert Krambrink, Amy Coakley, Eoin Greaves, Wayne L. Zolopa, Andrew Reichman, Richard Godfrey, Catherine Hirsch, Martin Kuritzkes, Daniel R. CA AIDS Clinical Trials Grp 5211 Team TI Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-infected, treatment experienced patients: AIDS clinical trials group 5211 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 16th International AIDS Conference CY AUG 13-18, 2006 CL Toronto, CANADA ID ACTIVE ANTIRETROVIRAL THERAPY; ENTRY INHIBITORS; HIV-INFECTION; MALIGNANCIES; FUSION; INDIVIDUALS; ENFUVIRTIDE; ANTAGONIST; MUTATION; DISEASE AB Background. Vicriviroc, an investigational CCR5 inhibitor, demonstrated short- term antiretroviral activity in a phase 1 study. Methods. The present study was a double- blind, randomized phase 2 study of vicriviroc in treatment- experienced, human immunodeficiency virus ( HIV) - infected subjects experiencing virologic failure while receiving a ritonavir- containing regimen with an HIV- 1 RNA level >= 5000 copies/ mL and CCR5- using virus. Vicriviroc at 5, 10, or 15 mg or placebo was added to the failing regimen for 14 days, after which the antiretroviral regimen was optimized. The primary end point was the change in plasma HIV- 1 RNA levels at day 14; secondary end points included safety/ tolerability and HIV- 1 RNA changes at week 24. Results. One hundred eighteen subjects were randomized with a median HIV- 1 RNA level of 36,380 ( 4.56 log 10) copies/ mL and a median CD4 cell count of 146 cells/ mm(3). At 14 days and 24 weeks, mean changes in HIV1 RNA level ( log 10 copies/ mL) were greater in the vicriviroc groups ( - 0.87 and - 1.51 [ 5 mg], - 1.15 and - 1.86 [ 10 mg], and - 0.92 and - 1.68 [ 15 mg]) than in the placebo group (+ 0.06 and - 0.29) (P < 0,29). Grade 3/ 4 adverse events were similar across groups. Malignancies occurred in 6 subjects randomized to vicriviroc and in 2 to placebo. Conclusions. In HIV- 1 - infected, treatment- experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment- experienced patients is warranted. C1 Cornell Univ, Weill Med Coll, Cornell HIV Clin Trials Unit, New York, NY 10021 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. NIH, Div AIDS, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Monogram Biosci Inc, San Francisco, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Gulick, RM (reprint author), Cornell Univ, Weill Med Coll, Cornell HIV Clin Trials Unit, Box 566,525 E 68th St, New York, NY 10021 USA. EM rgulick@med.cornell.edu FU NCRR NIH HHS [M01-RR00047, M01-RR00052, M01-RR00096, M01-RR00046, M01-RR00044, M01-RR00051]; NIAID NIH HHS [AI-27661, AI-39439, AI-46370, AI-46381, AI-69418, AI-69423, AI-69432, AI-69434, AI-69450, AI-69465, AI-69472, AI-69474, AI-69494, AI-69502, P30-AI-50410, U01-AI-68636, AI-25859, AI-32783, AI-34853, AI-68634, AI-69411, AI-69419, AI-69424, AI-69471, AI-69495, AI-69501, AI-69532, AI-69556, K23 AI-55038, K24-AI-51966, P30-AI-45008] NR 28 TC 190 Z9 201 U1 0 U2 3 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 JUL 15 PY 2007 VL 196 IS 2 BP 304 EP 312 DI 10.1086/518797 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186UF UT WOS:000247803100019 PM 17570119 ER PT J AU Joos, B Fischer, M Schweizer, A Kuster, H Boni, J Wong, JK Weber, R Trkola, A Gunthard, HF AF Joos, Beda Fischer, Marek Schweizer, Andreas Kuster, Herbert Boeni, Juerg Wong, Joseph K. Weber, Rainer Trkola, Alexandra Guenthard, Huldrych F. TI Positive in vivo selection of the HIV-1 envelope protein gp120 occurs at surface-exposed regions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN ID STRUCTURED TREATMENT INTERRUPTIONS; VIRUS TYPE-1 INFECTION; T-CELL RESPONSES; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; IMMUNODEFICIENCY; EVOLUTION; NEUTRALIZATION; ACCESSIBILITY; GLYCOPROTEIN AB The rapid evolution of human immunodeficiency virus ( HIV) envelope represents a major challenge to vaccine and drug development, particularly because the underlying mechanisms are not completely understood. To explore whether distinct patterns of positive selection within the envelope glycoprotein ( gp) 120 exist and are associated with functionally relevant domains, we conducted a long- term survey of sequence evolution in 20 HIV- 1 - infected persons who interrupted antiretroviral therapy. In total, 1753 clonal sequences encompassing the C2- V3- C3 region of gp120 were derived. Strikingly, positively selected amino acids mapped almost exclusively (P=.0003) to externally accessible residues on the gp120 crystal structure. The current understanding of envelope structure and function associates the main determinants of viral entry and the targets for neutralizing antibodies with these exterior regions of gp120, strongly suggesting that the observed adaptive evolution of these sites occurs in response to respective selective forces. C1 Univ Zurich Hosp, Dept Med, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland. Swiss Natl Ctr Retroviruses, Zurich, Switzerland. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Joos, B (reprint author), Univ Zurich Hosp, Dept Med, Div Infect Dis & Hosp Epidemiol, Ramistr 100, CH-8091 Zurich, Switzerland. EM beda.joos@usz.ch; huldrych.guenthard@usz.ch RI Joos, Beda/D-5547-2009; gunthard, huldrych/F-1724-2011; Kuster, Herbert/A-3912-2013; Infektiologie, USZ/A-6921-2011; Weber, Rainer/D-5175-2012; Trkola, Alexandra/K-2115-2012 OI Joos, Beda/0000-0002-3082-8875; gunthard, huldrych/0000-0002-1142-6723; Trkola, Alexandra/0000-0003-1013-876X FU NINDS NIH HHS [R01 NS51132] NR 30 TC 10 Z9 11 U1 1 U2 3 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 JUL 15 PY 2007 VL 196 IS 2 BP 313 EP 320 DI 10.1086/518935 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186UF UT WOS:000247803100020 PM 17570120 ER PT J AU Weintraub, D Saboe, K Stern, MB AF Weintraub, Daniel Saboe, Kirsten Stern, Matthew B. TI Effect of age on geriatric depression scale performance in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; depression; age; Geriatric Depression Scale ID NONMOTOR SYMPTOMS; RATING-SCALE; VALIDITY; INVENTORY; HAMILTON AB The purpose of this study was to compare the validity of the 15-item Geriatric Depression Scale (GDS-15) in nonelderly (< 65 years), young-elderly (age, 65-75), and old-elderly (> 75 years) patients with Parkinson's disease (PD). 57 nonelderly, 88 young-elderly, and 81 old-elderly PD patients were administered the GDS-15 and the Structured Clinical Interview for DSM-IV depression module. Receiver-operating characteristic (ROC) curves were plotted for GDS-15 scores against a DSM-IV diagnosis of major or minor depression. The discriminant validity of the GDS-15 was high for nonelderly, young-elderly, and old-elderly subjects (ROC area under curve = 0.92, 0.91, and 0.95, respectively), with optimal dichotomization at a cut-off of 415 (85% sensitivity and 84% specificity in nonelderly; 89% sensitivity and 82% specificity in young-elderly) and 5/6 (90% sensitivity and 90% specificity in old-elderly). In conclusion, the GDS-15 has comparable validity in younger and older PD patients, suggesting its appropriateness as a depression screening instrument in PD patients of all ages. (c) 2007 Movement Disorder Society C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3535 Market St,Rm 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894, K23 MH067894-04]; PHS HHS [NIMH 067894] NR 21 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL 15 PY 2007 VL 22 IS 9 BP 1331 EP 1335 DI 10.1002/mds.21369 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 197BG UT WOS:000248527500021 PM 17546674 ER PT J AU Sharon, D Hamalainen, MS Tootell, RBH Halgren, E Belliveau, JW AF Sharon, Dahlia Hamalainen, Matti S. Tootell, Roger B. H. Halgren, Eric Belliveau, John W. TI The advantage of combining MEG and EEG: Comparison to fMRI in focally stimulated visual cortex SO NEUROIMAGE LA English DT Article ID FUNCTIONAL MRI; NEURONAL-ACTIVITY; HUMAN BRAIN; CEREBRAL-CORTEX; SOMATOSENSORY CORTEX; SOURCE LOCALIZATION; CORTICAL ACTIVITY; AREAS V1; MODEL; RESOLUTION AB To exploit the high (millisecond) temporal resolution of magnetoencephalography (MEG) and electroencephalography (EEG) for measuring neuronal dynamics within well-defined brain regions, it is important to quantitatively assess their localizing ability. Previous modeling studies and empirical data suggest that a combination of MEG and EEG signals should yield the most accurate localization, due to their complementary sensitivities. However, these two modalities have rarely, been explicitly combined for source estimation in studies of recorded brain activity, and a quantitative empirical assessment of their abilities, combined and separate, is currently lacking. Here we studied early visual responses to focal Gabor patches flashed during subject fixation. MEG and EEG data were collected simultaneously and were compared with the functional MRI (fMRI) localization produced by identical stimuli in the same subjects. This allowed direct evaluation of the localization accuracy of separate and combined MEG/EEG inverse solutions. We found that the localization accuracy of the combined MEG + EEG solution was consistently better than that of either modality alone, using three different source estimation approaches. Further analysis suggests that this improved localization is due to the different properties of the two imaging modalities rather than simply due to increased total channel number. Thus, combining MEG and EEG data is important for high-resolution spatiotemporal studies of the human brain. Published by Elsevier Inc. C1 Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, MGH HMS,Dept Radiol, Charlestown, MA 02129 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sharon, D (reprint author), Univ Calif San Diego, Dept Radiol, Multimedia Imaging Lab, La Jolla, CA 92093 USA. EM dahlia@nmr.mgh.hanard.edu RI Hamalainen, Matti/C-8507-2013 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NINDS NIH HHS [R01 NS037462-05, NS18741, NS37462, NS44623, R01 NS018741, R01 NS037462, R01 NS037462-04, R01 NS037462-06, R01 NS037462-07, R01 NS044623, R56 NS037462] NR 70 TC 91 Z9 92 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 15 PY 2007 VL 36 IS 4 BP 1225 EP 1235 DI 10.1016/j.neuroimage.2007.03.066 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 191SN UT WOS:000248152400016 PM 17532230 ER PT J AU Moon, SY Barton, JJS Mikulski, S Polli, FE Cain, MS Vangel, M Hamalainen, MS Manoach, DS AF Moon, So Young Barton, Jason J. S. Mikulski, Szymon Polli, Frida E. Cain, Matthew S. Vangel, Mark Hamalainen, Matti S. Manoach, Dara S. TI Where left becomes right: A magnetoencephalographic study of sensorimotor transformation for antisaccades SO NEUROIMAGE LA English DT Article DE intraparietal sulcus; frontal eye field; antisaccade; saccade; metoencephalography; sensorimotor transformation ID FRONTAL EYE FIELD; POSTERIOR PARIETAL CORTEX; LATERAL INTRAPARIETAL AREA; VISUALLY-GUIDED SACCADES; CORTICAL ACTIVITY; NEURAL SELECTION; CEREBRAL-CORTEX; SINGLE NEURONS; MACAQUE; MEMORY AB To perform a saccadic response to a visual stimulus, a 'sensorimotor transformation' is required (i.e., transforming stimulus location into a motor command). Where in the brain is this accomplished? While previous monkey neurophysiology and human fMRI studies examined either parietal cortex or frontal eye field, we studied both of these regions simultaneously using magnetoencephalography (MEG). Nineteen healthy participants performed a pseudorandom series of prosaccades and antisaccades during MEG. Antisaccades require a saccade in the direction opposite a suddenly appearing stimulus. We exploited this dissociation between stimulus and saccadic direction to identify cortical regions that show early activity for a contralateral stimulus and late activity for a contralateral saccade. We found that in the left hemisphere both the intraparietal sulcus and the frontal eye field showed a pattern of activity consistent with sensorimotor transformation - a transition front activity reflecting the direction of the stimulus to that representing the saccadic goal. These findings suggest that sensorimotor transformation is the product of coordinated activity across the intraparietal sulcus and frontal eye field, key components of a cortical network for saccadic generation. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ British Columbia, Dept Neurol, Vancouver, BC V6T 1Z4, Canada. Univ British Columbia, Dept Ophthalmol, Vancouver, BC V6T 1Z4, Canada. Univ British Columbia, Dept Visual Sci, Vancouver, BC V6T 1Z4, Canada. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Ajou Univ, Sch Med, Dept Neurol, Suwon 441749, South Korea. Massachusetts Gen Hosp, Harvard Med Sch, Dept Psychiat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02215 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, 36 First Ave,room 420, Hillsborough 02129, North Ireland. EM dara@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; Hamalainen, Matti/C-8507-2013; OI Cain, Matthew/0000-0002-3305-0464 FU NCRR NIH HHS [P41 RR014075, R01 RR16594-01A1, P41-RR14075, U24 RR021382, R01 RR016594]; NIMH NIH HHS [R01 MH031340, P01 MH31154, R01 MH067720, R01 MH67720, R01 MH067720-03, R01 MH31340]; PHS HHS [BIRN002] NR 48 TC 48 Z9 48 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 15 PY 2007 VL 36 IS 4 BP 1313 EP 1323 DI 10.1016/j.neuroimage.2007.04.040 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 191SN UT WOS:000248152400025 PM 17537647 ER PT J AU Sachs, DH Yamada, K Robson, SC Fishman, JA Shimizu, A Colvin, RB Sykes, M AF Sachs, David H. Yamada, Kazuhiko Robson, Simon C. Fishman, Jay A. Shimizu, Akira Colvin, Robert B. Sykes, Megan TI GaIT-KO pigs: Is the cup half empty or half full? SO TRANSPLANTATION LA English DT Editorial Material ID THYMIC LOBE TRANSPLANTATION; TOLERANCE INDUCTION; MIXED CHIMERISM; MINIATURE SWINE; T-CELL; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; VASCULARIZED THYMUS; BABOONS; XENOTRANSPLANTATION; REJECTION C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Transplant Ctr, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [SP01HL 18646]; NIAID NIH HHS [P01 AI045897, U01 AI066331, U01 AI066331-01] NR 21 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2007 VL 84 IS 1 BP 12 EP 14 DI 10.1097/01.tp.0000269729.68625.08 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 191BJ UT WOS:000248104500004 PM 17627230 ER PT J AU Spinewine, A Schmader, KE Barber, N Hughes, C Lapane, KL Swine, C Hanlon, JT AF Spinewine, Anne Schmader, Kenneth E. Barber, Nick Hughes, Carmel Lapane, Kate L. Swine, Christian Hanlon, Joseph T. TI Prescribing in elderly people 1 - Appropriate prescribing in elderly people: how well can it be measured and optimised? SO LANCET LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; INAPPROPRIATE MEDICATION USE; DRUG-RELATED MORBIDITY; NURSING-HOME RESIDENTS; QUALITY-OF-CARE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CLINICAL PHARMACIST INTERVENTION; HOSPITALIZED OLDER-ADULTS; LONG-TERM-CARE; POTENTIALLY INAPPROPRIATE AB Prescription of medicines is a fundamental component of the care of elderly people, and optimisation of drug prescribing for this group of patients has become an important public-health issue worldwide. Several characteristics of ageing and geriatric medicine affect medication prescribing for elderly people and render the selection of appropriate pharmacotherapy a challenging and complex process. In the first paper in this series we aim to define and categorise appropriate prescribing in elderly people, critically review the instruments that are available to measure it and discuss their predictive validity, critically review recent randomised controlled intervention studies that assessed the effect of optimisation strategies on the appropriateness of prescribing in elderly people, and suggest directions for future research and practice. C1 Univ Catholique Louvain, Ctr Clin Pharm, Sch Pharm, B-1200 Brussels, Belgium. Duke Univ, Med Ctr, Sch Med, Dept Geriatr Med, Durham, England. Duke Univ, Med Ctr, Aging Ctr, Durham, England. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. Univ London, Sch Pharm, Dept Practice & Policy, London, England. Queens Univ Belfast, Sch Pharm, Belfast, Antrim, North Ireland. Brown Med Sch, Dept Community Hlth, Providence, RI USA. Univ Catholique Louvain, Mt Godinne Univ Hosp, Dept Geriatr Med, B-1200 Brussels, Belgium. Univ Pittsburgh, Inst Aging, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Spinewine, A (reprint author), Univ Catholique Louvain, Ctr Clin Pharm, Sch Pharm, UCL 73-70,Ave E Mounier 73, B-1200 Brussels, Belgium. EM anne.spinewine@facm.ucl.ac.be FU AHRQ HHS [U18HS016394]; NIA NIH HHS [P30 AG024827, R01 AG027017, R01AG14158]; NIAID NIH HHS [K24AI051324-01]; NICHD NIH HHS [K12HD049109] NR 152 TC 369 Z9 387 U1 8 U2 51 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 14 PY 2007 VL 370 IS 9582 BP 173 EP 184 DI 10.1016/S0140-6736(07)61091-5 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 190WP UT WOS:000248091600032 PM 17630041 ER PT J AU Zhang, HM Qin, GJ Liang, G Li, JA Chiu, I Barrington, RA Liu, DX AF Zhang, Haimou Qin, Gangjian Liang, Gang Li, Jinan Chiu, Isaac Barrington, Robert A. Liu, Dongxu TI Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE complement; endothelium; signaling; adhesion molecule ID MULTIPLE ORGAN FAILURE; NF-KAPPA-B; PLASMA EXTRAVASATION; LEUKOCYTE ADHERENCE; ESTERASE INHIBITOR; NITRIC-OXIDE; LIPOPOLYSACCHARIDE; EXPRESSION; ENDOTOXIN; APOPTOSIS AB Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-kappa B activation and nuclear translocation in an I kappa B alpha-dependent manner. The inhibitory effects were associated with reduction of inhibitor I kappa B kinase activity and stabilization of the NF-KB inhibitor I kappa B. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations. (C) 2007 Elsevier Inc. All rights reserved. C1 Hubei Univ, Sch Life Sci, Ctr Infect & Immun Res, Wuhan, Hubei, Peoples R China. Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Liu, DX (reprint author), Hubei Univ, Sch Life Sci, Ctr Infect & Immun Res, Wuhan, Hubei, Peoples R China. EM dxliu001@yahoo.com NR 40 TC 4 Z9 4 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 13 PY 2007 VL 358 IS 4 BP 1120 EP 1127 DI 10.1016/j.bbrc.2007.05.058 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 178LA UT WOS:000247221000027 PM 17521609 ER PT J AU Oshiro, N Takahashi, R Yoshino, KI Tanimura, K Nakashima, A Eguchi, S Miyamoto, T Hara, K Takehana, K Avruch, J Kikkawa, U Yonezawa, K AF Oshiro, Noriko Takahashi, Rinako Yoshino, Ken-ichi Tanimura, Keiko Nakashima, Akio Eguchi, Satoshi Miyamoto, Takafumi Hara, Kenta Takehana, Kenji Avruch, Joseph Kikkawa, Ushio Yonezawa, Kazuyoshi TI The proline-rich akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P70 S6 KINASE; REPRESSOR PHAS-I; PROTEIN-KINASE; TUBEROUS SCLEROSIS; SIGNALING PATHWAYS; BINDING PARTNER; CELL-SURVIVAL; GROWTH-FACTOR; EIF-4E BP1; AMINO-ACID AB The proline-rich Akt substrate of 40 kilodaltons (PRAS40) was identified as a raptor-binding protein that is phosphorylated directly by mammalian target of rapamycin ( mTOR) complex 1 (mTORC1) but not mTORC2 in vitro, predominantly at PRAS40 (Ser(183)). The binding of S6K1 and 4E-BP1 to raptor requires a TOR signaling (TOS) motif, which contains an essential Phe followed by four alternating acidic and small hydrophobic amino acids. PRAS40 binding to raptor was severely inhibited by mutation of PRAS40 (Phe(129) to Ala). Immediately carboxyl-terminal to Phe(129) are two small hydrophobic amino acid followed by two acidic residues. PRAS40 binding to raptor was also abolished by mutation of the majormTORC1phosphorylation site, Ser(183), to Asp. PRAS40 (Ser(183)) was phosphorylated in intact cells; this phosphorylation was inhibited by rapamycin, by 2- deoxyglucose, and by overexpression of the tuberous sclerosis complex heterodimer. PRAS40 ( Ser183) phosphorylation was also inhibited reversibly by withdrawal of all or of only the branched chain amino acids; this inhibition was reversed by overexpression of the Rheb GTPase. Over-expressed PRAS40 suppressed the phosphorylation of S6K1 and 4E-BP1 at their rapamycin-sensitive phosphorylation sites, and reciprocally, overexpression of S6K1 or 4E-BP1 suppressed phosphorylation of PRAS40 (Ser(183)) and its binding to raptor. RNA interference-induced depletion of PRAS40 enhanced the amino acid-stimulated phosphorylation of both S6K1 and 4E-BP1. These results establish PRAS40 as a physiological mTORC1 substrate that contains a variant TOS motif. Moreover, they indicate that the ability of raptor to bind endogenous substrates is limiting for the activity of mTORC1 in vivo and is therefore a potential locus of regulation. C1 Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. Kobe Univ, Sch Med, Dept Internal & Geriatr Med, Kobe, Hyogo 6500017, Japan. Ajinomoto Co Inc, Pharmaceut Res Labs, Kawasaki, Kanagawa 2108681, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Dept Mol Biol & Diabet Unit, Boston, MA 02114 USA. RP Avruch, J (reprint author), Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [CA 73818, R01 CA073818]; NIDDK NIH HHS [DK 17776, P30 DK040561, P30 DK040561-12, R37 DK017776] NR 49 TC 193 Z9 198 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 13 PY 2007 VL 282 IS 28 BP 20329 EP 20339 DI 10.1074/jbc.M702636200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 187AI UT WOS:000247819300036 PM 17517883 ER PT J AU Lee, JY Engelman, JA Cantley, LC AF Lee, Jennifer Y. Engelman, Jeffrey A. Cantley, Lewis C. TI Biochemistry - PI3K charges ahead SO SCIENCE LA English DT Editorial Material ID PHOSPHATIDYLINOSITOL 3'-KINASE; 3-KINASES C1 Harvard Univ, Sch Med, Dept Biol Syst Engn, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Lee, JY (reprint author), Harvard Univ, Sch Med, Dept Biol Syst Engn, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 9 TC 20 Z9 21 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 13 PY 2007 VL 317 IS 5835 BP 206 EP 207 DI 10.1126/science.1146073 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 189DC UT WOS:000247968600027 PM 17626872 ER PT J AU Lee, TH Torchiana, DF Lock, JE AF Lee, Thomas H. Torchiana, David F. Lock, James E. TI Is zero the ideal death rate? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Partners Healthcare Syst, Boston, MA 02199 USA. Massachusetts Gen Phys Org, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Lee, TH (reprint author), Partners Healthcare Syst, Boston, MA 02199 USA. NR 4 TC 20 Z9 20 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 JUL 12 PY 2007 VL 357 IS 2 BP 111 EP 113 DI 10.1056/NEJMp078025 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 188NX UT WOS:000247927700004 PM 17625122 ER PT J AU Sheth, KN Greer, DM Gonzalez, RG Hedley-Whyte, ET Harris, NL Cagliero, E AF Sheth, Kevin N. Greer, David M. Gonzalez, R. Gilberto Hedley-Whyte, E. Tessa Harris, Nancy Lee Cagliero, Enrico TI Case 21-2007: A 58-year-old woman with headaches, weakness, and strokelike episodes - Severe microangiopathy characteristic of diabetic vasculopathy, with multiple cerebral infarcts. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTENSIVE INSULIN THERAPY; CENTRAL-NERVOUS-SYSTEM; CARDIOVASCULAR-DISEASE; MITOCHONDRIAL-DNA; ASSISTED SUICIDE; MELLITUS; SCLEROSIS; ABNORMALITIES; PATHOLOGY; MIGRAINE C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, 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 Sheth, KN (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 38 TC 0 Z9 0 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 JUL 12 PY 2007 VL 357 IS 2 BP 164 EP 173 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 188NX UT WOS:000247927700012 ER PT J AU Challa, M Malladi, S Pellock, BJ Dresnek, D Varadarajan, S Yin, YW White, K Bratton, SB AF Challa, Madhavi Malladi, Srinivas Pellock, Brett J. Dresnek, Douglas Varadarajan, Shankar Yin, Y. Whitney White, Kristin Bratton, Shawn B. TI Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease SO EMBO JOURNAL LA English DT Article DE apoptosis; DIAP1; dOmi; DRONC; Drosophila ID PROMOTES CELL-DEATH; CYTOCHROME-C; CASPASE ACTIVATION; APOPTOSIS PROTEINS; APAF-1 APOPTOSOME; REAPER; DIAP1; GRIM; INHIBITION; HID AB Although essential in mammals, in flies the importance of mitochondrial outer membrane permeabilization for apoptosis remains highly controversial. Herein, we demonstrate that Drosophila Omi (dOmi), a fly homologue of the serine protease Omi/HtrA2, is a developmentally regulated mitochondrial intermembrane space protein that undergoes processive cleavage, in situ, to generate two distinct inhibitor of apoptosis (IAP) binding motifs. Depending upon the proapoptotic stimulus, mature dOmi is then differentially released into the cytosol, where it binds selectively to the baculovirus IAP repeat 2 (BIR2) domain in Drosophila IAP1 (DIAP1) and displaces the initiator caspase DRONC. This interaction alone, however, is insufficient to promote apoptosis, as dOmi fails to displace the effector caspase DrICE from the BIR1 domain in DIAP1. Rather, dOmi alleviates DIAP1 inhibition of all caspases by proteolytically degrading DIAP1 and induces apoptosis both in cultured cells and in the developing fly eye. In summary, we demonstrate for the first time in flies that mitochondrial permeabilization not only occurs during apoptosis but also results in the release of a bona fide proapoptotic protein. C1 Univ Texas, Coll Pharm, Div Pharmacol & Toxicol, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. RP Bratton, SB (reprint author), Univ Texas, Coll Pharm, Div Pharmacol & Toxicol, 1 Univ Stn A1915,2409 Univ Ave, Austin, TX 78712 USA. EM sbbratton@mail.utexas.edu RI White, Kristin/D-7936-2013 FU NIGMS NIH HHS [GM55568, R01 GM055568] NR 47 TC 35 Z9 38 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 11 PY 2007 VL 26 IS 13 BP 3144 EP 3156 DI 10.1038/sj.emboj.7601745 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190DP UT WOS:000248038500010 PM 17557079 ER PT J AU Kim, D Nguyen, MD Dobbin, MM Fischer, A Sananbenesi, F Rodgers, JT Delalle, I Baur, JA Sui, GC Armour, SM Puigserver, P Sinclair, DA Tsai, LH AF Kim, Dohoon Nguyen, Minh Dang Dobbin, Matthew M. Fischer, Andre Sananbenesi, Farahnaz Rodgers, Joseph T. Delalle, Ivana Baur, Joseph A. Sui, Guangchao Armour, Sean M. Puigserver, Pere Sinclair, David A. Tsai, Li-Huei TI SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis SO EMBO JOURNAL LA English DT Article DE AD; ALS; neurodegeneration; p25; SIRT1 ID LIFE-SPAN EXTENSION; MOTOR-NEURON DEGENERATION; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; CELL-SURVIVAL; TRANSCRIPTION FACTORS; CDK5; P25; NAD; P35 AB A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention. C1 MIT, Tsai Brain & Cognit Sci, Boston, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. Univ Gottingen, Sch Med, Max Planck Soc, D-3400 Gottingen, Germany. MIT, RIKEN, Neurosci Res Ctr, Howard Hughes Med Inst,Dept Brain & Cognit Sci, Boston, MA USA. Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Tsai, LH (reprint author), MIT, Tsai Brain & Cognit Sci, 32 Vassar St, Boston, MA 02139 USA. EM david_sinclair@hms.harvard.edu; lhtsai@mit.edu RI Baur, Joseph/D-8163-2011; OI Sinclair, David/0000-0002-9936-436X; Baur, Joseph/0000-0001-8262-6549 FU NIA NIH HHS [P01 AG027916] NR 51 TC 541 Z9 564 U1 15 U2 81 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 11 PY 2007 VL 26 IS 13 BP 3169 EP 3179 DI 10.1038/sj.emboj.7601758 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190DP UT WOS:000248038500012 PM 17581637 ER PT J AU Zhang, NH Wei, WZ Mody, I Houser, CR AF Zhang, Nianhui Wei, Weizheng Mody, Istvan Houser, Carolyn R. TI Altered localization of GABAA receptor subunits on dentate granule cell dendrites influences tonic and phasic inhibition in a mouse model of epilepsy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE immunogold labeling; electron microscopy; dentate gyrus; tonic inhibition; neurosteroids; pilocarpine; temporal lobe; epilepsy ID TEMPORAL-LOBE EPILEPSY; MESSENGER-RNA EXPRESSION; DELTA-SUBUNIT; RAT HIPPOCAMPUS; GAMMA-2 SUBUNITS; DEFICIENT MICE; OVARIAN CYCLE; SYNAPSES; NEURONS; GYRUS AB Complex changes in GABA(A) receptors (GABA(A)Rs) in animal models of temporal lobe epilepsy during the chronic period include a decrease in the delta subunit and increases in the alpha 4 and gamma 2 subunits in the dentate gyrus. We used postembedding immunogold labeling to determine whether the subcellular locations of these subunits were also altered in pilocarpine-treated epileptic mice, and related functional changes were identified electrophysiologically. The ultrastructural studies confirmed a decrease in delta subunit labeling at perisynaptic locations in the molecular layer of the dentate gyrus where these subunits are critical for tonic inhibition. Unexpectedly, tonic inhibition in dentate granule cells was maintained in the epileptic mice, suggesting compensation by other GABA(A)Rs. An insensitivity of the tonic current to the neurosteroid tetrahydrodeoxy-corticosterone was consistent with decreased expression of the delta subunit. In the pilocarpine-treated mice, alpha 4 subunit labeling remained at perisynaptic locations, but increased gamma 2 subunit labeling was also found at many perisynaptic locations on granule cell dendrites, consistent with a shift of the gamma 2 subunit from synaptic to perisynaptic locations and potential partnership of the alpha 4 and gamma 2 subunits in the epileptic animals. The decreased gamma 2 labeling near the center of synaptic contacts was paralleled by a corresponding decrease in the dendritic phasic inhibition of granule cells in the pilocarpine-treated mice. These GABA(A) R subunit changes appear to impair both tonic and phasic inhibition, particularly at granule cell dendrites, and could reduce the adaptive responses of the GABA system in temporal lobe epilepsy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU BLRD VA [I01 BX000404]; NINDS NIH HHS [NS002808, NS035985, NS051311] NR 61 TC 126 Z9 128 U1 0 U2 2 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 JUL 11 PY 2007 VL 27 IS 28 BP 7520 EP 7531 DI 10.1523/JNEUROSCI.1555-07.2007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 191RD UT WOS:000248147900017 PM 17626213 ER PT J AU Gabel, CV Gabel, H Pavlichin, D Kao, A Clark, DA Samuel, ADT AF Gabel, Christopher V. Gabel, Harrison Pavlichin, Dmitri Kao, Albert Clark, Damon A. Samuel, Aravinthan D. T. TI Neural circuits mediate electrosensory behavior in Caenorhabditis elegans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C. elegans; electrical stimulation; motor control; movement (motion motor activity); navigation; sensorimotor ID C-ELEGANS; CHEMOSENSORY NEURONS; ESCHERICHIA-COLI; DECISION-MAKING; ELECTRIC-FIELDS; SENSORY NEURONS; GENE; THERMOTAXIS; RESPONSES; RECEPTOR AB The nematode Caenorhabditis elegans deliberately crawls toward the negative pole in an electric field. By quantifying the movements of individual worms navigating electric fields, we show that C. elegans prefers to crawl at specific angles to the direction of the electric field in persistent periods of forward movement and that the preferred angle is proportional to field strength. C. elegans reorients itself in response to time-varying electric fields by using sudden turns and reversals, standard reorientation maneuvers that C. elegans uses during other modes of motile behavior. Mutation or laser ablation that disrupts the structure and function of amphid sensory neurons also disrupts electrosensory behavior. By imaging intracellular calcium dynamics among the amphid sensory neurons of immobilized worms, we show that specific amphid sensory neurons are sensitive to the direction and strength of electric fields. We extend our analysis to the motor level by showing that specific interneurons affect the utilization of sudden turns and reversals during electrosensory steering. Thus, electrosensory behavior may be used as a model system for understanding how sensory inputs are transformed into motor outputs by the C. elegans nervous system. C1 Harvard Univ, Ctr Brain Sci, Dept Phys, Cambridge, MA 02138 USA. Harvard Med Sch, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Samuel, ADT (reprint author), Harvard Univ, Ctr Brain Sci, Dept Phys, 17 Oxford St, Cambridge, MA 02138 USA. EM samuel@physics.harvard.edu OI Clark, Damon/0000-0001-8487-700X NR 48 TC 42 Z9 58 U1 2 U2 5 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 JUL 11 PY 2007 VL 27 IS 28 BP 7586 EP 7596 DI 10.1523/JNEUROSCI.0775-07.2007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 191RD UT WOS:000248147900024 PM 17626220 ER PT J AU Biglione, S Byers, SA Price, JP Nguyen, VT Bensaude, O Price, DH Maury, W AF Biglione, Sebastian Byers, Sarah A. Price, Jason P. Nguyen, Van Trung Bensaude, Olivier Price, David H. Maury, Wendy TI Inhibition of HIV-I replication by P-TEFb inhibitors DRB, seliciclib and flavopiridol correlates with release of free P-TEFb from the large, inactive form of the complex SO RETROVIROLOGY LA English DT Article ID RNA-POLYMERASE-II; DEPENDENT KINASE INHIBITORS; BROMODOMAIN PROTEIN BRD4; PHASE-II; TRANSCRIPTIONAL ACTIVATION; ADVANCED MALIGNANCIES; 7SK SNRNA; ELONGATION; VIRUS; CDK9 AB Background: The positive transcription elongation factor, P-TEFb, comprised of cyclin dependent kinase 9 (Cdk9) and cyclin T1, T2 or K regulates the productive elongation phase of RNA polymerase II ( Pol II) dependent transcription of cellular and integrated viral genes. P-TEFb containing cyclin T1 is recruited to the HIV long terminal repeat (LTR) by binding to HIV Tat which in turn binds to the nascent HIV transcript. Within the cell, P-TEFb exists as a kinase-active, free form and a larger, kinase-inactive form that is believed to serve as a reservoir for the smaller form. Results: We developed a method to rapidly quantitate the relative amounts of the two forms based on differential nuclear extraction. Using this technique, we found that titration of the P-TEFb inhibitors flavopiridol, DRB and seliciclib onto HeLa cells that support HIV replication led to a dose dependent loss of the large form of P-TEFb. Importantly, the reduction in the large form correlated with a reduction in HIV-1 replication such that when 50% of the large form was gone, HIV-1 replication was reduced by 50%. Some of the compounds were able to effectively block HIV replication without having a significant impact on cell viability. The most effective P-TEFb inhibitor flavopiridol was evaluated against HIV-1 in the physiologically relevant cell types, peripheral blood lymphocytes (PBLs) and monocyte derived macrophages (MDMs). Flavopiridol was found to have a smaller therapeutic index (LD50/IC50) in long term HIV-1 infectivity studies in primary cells due to greater cytotoxicity and reduced efficacy at blocking HIV-1 replication. Conclusion: Initial short term studies with P-TEFb inhibitors demonstrated a dose dependent loss of the large form of P-TEFb within the cell and a concomitant reduction in HIV-1 infectivity without significant cytotoxicity. These findings suggested that inhibitors of P-TEFb may serve as effective anti-HIV-1 therapies. However, longer term HIV-1 replication studies indicated that these inhibitors were more cytotoxic and less efficacious against HIV-1 in the primary cell cultures. C1 Univ Iowa, Inst Mol & Cellular Biol, Iowa City, IA 52242 USA. Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. Ecole Normale Super, Lab Regulat Express Genet, F-75231 Paris, France. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. RP Maury, W (reprint author), Univ Iowa, Inst Mol & Cellular Biol, Iowa City, IA 52242 USA. EM biglione@cbrinstitute.org; byerssa@ohsu.edu; jason-price@uiowa.edu; vtnguyen@biologie.ens.fr; bensaude@wotan.ens.fr; david-price@uiowa.edu; wendy-maury@uiowa.edu RI Price, David/F-6173-2010 FU NIAID NIH HHS [AI54340, AI54340-03S1, R01 AI054340] NR 55 TC 66 Z9 68 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUL 11 PY 2007 VL 4 AR 47 DI 10.1186/1742-4690-4-47 PG 12 WC Virology SC Virology GA 204EO UT WOS:000249026700001 PM 17625008 ER PT J AU Fifer, MA AF Fifer, Michael A. TI Most fully informed patients choose septal ablation over septal myectomy SO CIRCULATION LA English DT Editorial Material ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; VENTRICULAR OUTFLOW TRACT; REDUCTION THERAPY; ALCOHOL ABLATION; FOLLOW-UP; TRANSCORONARY ABLATION; SYMPTOMATIC PATIENTS; SURGICAL-MANAGEMENT; MYOCARDIAL ABLATION; SUBAORTIC STENOSIS C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St,Gray Bigelow Bldg,Ste 800,Mailstop 84, Boston, MA 02114 USA. EM mfifer@partners.org NR 63 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 10 PY 2007 VL 116 IS 2 BP 207 EP 216 DI 10.1161/CIRCULATIONAHA.107.688135 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188ES UT WOS:000247902600013 PM 17620520 ER PT J AU Ribichini, F Joner, M Ferrero, V Finn, AV Crimins, J Nakazawa, G Acampado, E Kolodgie, FD Vassanelli, C Virmani, R AF Ribichini, Flavio Joner, Michael Ferrero, Valeria Finn, Aloke V. Crimins, Johanna Nakazawa, Gaku Acampado, Eduardo Kolodgie, Frank D. Vassanelli, Corrado Virmani, Renu TI Effects effects of oral prednisone after stenting in a rabbit model of established atherosclerosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DRUG-ELUTING STENTS; PORCINE CORONARY MODEL; TAXUS-IV TRIAL; FACTOR-KAPPA-B; SLOW-RELEASE; PACLITAXEL; IMPLANTATION; RESTENOSIS; PREVENTION; RESPONSES AB Objectives The aim of this study was to compare the effects of systemic prednisone in combination with a bare-metal stent (BMS) or a paclitaxel-eluting stent (Taxus, Boston Scientific Corp., Natick, Massachusetts) on neointimal inhibition and vessel healing in an atherosclerotic rabbit model. Background Inflammation plays a critical role in neointimal formation after coronary artery stenting. The efficacy of immunosuppressive doses of oral prednisone to inhibit in-stent neointimal proliferation was compared with BMS and with a commercially available paclitaxel-eluting stent (Taxus) in a rabbit model of established atherosclerosis. Methods Bilateral iliac artery injury in atherosclerotic New Zealand White rabbits fed an atherogenic diet was followed by stent implantation. Animals randomly received Taxus stents, BMS (Express, Boston Scientific Corp.) and placebo, or BMS and oral prednisone (2.1 mg/kg/day for the first 7 days, followed by 1.4 mg/kg/day for 14 days and 0.7 mg/kg/day for 21 days). Stented arterial segments were harvested at 42 days and processed for light microscopy, immunohistochemistry, and organoid culture. Results Compared with control subjects, prednisone-treated animals showed a 30% reduction in percent stenosis (p = 0.009), a 35% decrease in neointimal area (p < 0.003), and a 66% decrement in neointimal thickness (p < 0.001.). Taxus stents also reduced all 3 parameters significantly (-34%, -39%, and -83%, respectively), but showed significantly more inflammatory cells and fibrin deposition and less endothelialization compared with the other 2 groups. Plaque burden was equal among groups, as shown by the identical stent and vessel area, and no remodeling was observed. Conclusions Systemic prednisone treatment and Taxus stents reduce neointimal formation compared with BMS. The extent of neointimal reduction is similar between prednisone- and Taxus stent-treated animals; however, Taxus stents resulted in a significantly greater delay in healing. Targeting of inflammatory pathways after percutaneous coronary intervention may be an efficacious way to prevent restenosis without the long-term risk of late thrombosis. C1 Univ Verona, Div Cardiol, Osped Civile Maggiore, I-37100 Verona, Italy. Massachusetts Gen Hosp, Cardiac Unit, Dept Internal Med, Boston, MA 02114 USA. CVPath Inst Inc, Gaithersburg, MD USA. RP Virmani, R (reprint author), CVPath, Int Registry Pathol, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 20 TC 39 Z9 40 U1 1 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 JUL 10 PY 2007 VL 50 IS 2 BP 176 EP 185 DI 10.1016/j.jacc.2007.03.031 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 187ZE UT WOS:000247887200011 PM 17616304 ER PT J AU Seeley, WW Marty, FM Holmes, TM Upchurch, K Soiffer, RJ Antin, JH Baden, LR Bromfield, EB AF Seeley, W. W. Marty, F. M. Holmes, T. M. Upchurch, K. Soiffer, R. J. Antin, J. H. Baden, L. R. Bromfield, E. B. TI Post-transplant acute limbic encephalitis - Clinical features and relationship to HHV6 SO NEUROLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; HUMAN HERPESVIRUS-6 INFECTION; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; CEREBROSPINAL-FLUID; VARIANT-B; HUMAN-HERPESVIRUS-6 INFECTION; MULTIPLE-SCLEROSIS; SEVERE AMNESIA; RECIPIENT AB Background: Acute limbic encephalitis has been reported in the setting of treatment-related immunosuppression and attributed to human herpesvirus-6 (HHV6) infection. Clinical and laboratory features of the syndrome, however, have not been well characterized. Methods: We describe the clinical, EEG, MRI, and laboratory features of nine patients with acute limbic encephalitis after allogeneic hematopoietic stem cell transplantation (HSCT). To explore the relationship between HHV6 and this syndrome, we reviewed available CSF HHV6 PCR results from all HSCT patients seen at our center from March 17, 2003, through March 31, 2005. Results: Patients displayed a consistent and distinctive clinical syndrome featuring anterograde amnesia, the syndrome of inappropriate antidiuretic hormone secretion, mild CSF pleocytosis, and temporal EEG abnormalities, often reflecting clinical or subclinical seizures. MRI showed hyperintensities within the uncus, amygdala, entorhinal area, and hippocampus on T2, fluid-attenuated inversion recovery ( FLAIR), and diffusion-weighted imaging (DWI) sequences. CSF PCR assays for HHV6 were positive in six of nine patients on initial lumbar puncture. All patients were treated with foscarnet or ganciclovir. Cognitive recovery varied among long-term survivors. The one brain autopsy showed limbic gliosis and profound neuronal loss in amygdala and hippocampus. Among 27 HSCT patients with CSF tested for HHV6 over a 2-year period, positive results occurred only in patients with clinical limbic encephalitis. Conclusions: Patients undergoing allogeneic hematopoietic stem cell transplantation are at risk for post-transplant acute limbic encephalitis (PALE), a distinct neurologic syndrome. Treatment considerations should include aggressive seizure control and, possibly, antiviral therapy. PALE can be associated with the CSF presence of human herpesvirus-6, but the pathogenic role of the virus requires further exploration. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seeley, WW (reprint author), Univ Calif San Francisco, Memory & Aging Ctr, Box 1207, San Francisco, CA 94143 USA. EM wseeley@memory.ucsf.edu RI chen, xuanlan/H-4158-2011 NR 41 TC 125 Z9 130 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 10 PY 2007 VL 69 IS 2 BP 156 EP 165 DI 10.1212/01.wnl.0000265591.10200.d7 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 188ER UT WOS:000247902500006 PM 17620548 ER PT J AU Viswanathan, A Gschwendtner, A Guichard, JP Buffon, F Cumurciuc, R O'Sullivan, M Holtmannspotter, M Pachai, C Bousser, MG Dichgans, M Chabriat, H AF Viswanathan, A. Gschwendtner, A. Guichard, J.-P. Buffon, F. Cumurciuc, R. O'Sullivan, M. Holtmannspotter, M. Pachai, C. Bousser, M.-G. Dichgans, M. Chabriat, H. TI Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL SO NEUROLOGY LA English DT Article ID AUTOSOMAL-DOMINANT ARTERIOPATHY; SUBCORTICAL INFARCTS; CARDIOVASCULAR HEALTH; CEREBRAL MICROBLEEDS; DISEASE PROGRESSION; HISTOGRAM ANALYSIS; VASCULAR DEMENTIA; NOTCH3 MUTATIONS; BLOOD-PRESSURE; STROKE AB Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The disease is characterized by T2-hyperintense lesions (subcortical white matter lesions), T1-hypointense lesions (lacunar lesions), and T2*-weighted gradient-echo (GE) lesions (cerebral microhemorrhages [CMs]) visualized on clinical MRI sequences and is considered as a model of "pure" subcortical ischemic vascular dementia. Although numerous studies have investigated the impact of white matter lesions in patients with CADASIL, the clinical importance of lacunar lesions remains unknown. Our purpose was to examine the influence of the visible MRI markers in the disease, including the load of lacunar lesions on cognitive impairment and disability in CADASIL. Methods: We collected clinical data from 147 consecutive patients enrolled in an ongoing two-center prospective cohort study. Degree of disability was assessed by modified Rankin scale and Barthel index. Degree of cognitive impairment was assessed by Mattis Dementia Rating Scale and Mini-Mental Status Examination. T1-weighted, fluid-attenuated inversion recovery, and GE images were obtained on a 1.5-T MRI. Volume and location of lacunar lesions, white matter hyperintensities (WMHs), and CMs were assessed. Results: There was a significant independent association between age, volume of lacunar lesions, and global cognitive function scales when analyzed in a multivariable model. In contrast, WMHs and CMs had no independent influence on cognitive function. Disability in this cohort was associated with volume of lacunar lesions, CMs, systolic blood pressure, and age but not with WMHs. Conclusions: Among the lesions observed on conventional MRI in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the overall lacunar lesion burden seems to have the most important impact on cognitive function and disability. These findings suggest that preventive strategies to decrease the risk of lacunar lesions as observed on MRI may reduce disease-related impairment in CADASIL. These results suggest that lacunar lesions may also play a key role in disability and cognitive impairment in more common forms of small-vessel disease. C1 CHU Lariboisiere, APHP, Dept Neurol, Paris, France. CHU Lariboisiere, APHP, Dept Neuroradiol, Paris, France. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Univ Munich, Klinikum Grosshadern, Dept Neurol, D-8000 Munich, Germany. Univ Munich, Klinikum Grosshadern, Dept Neuroradiol, D-8000 Munich, Germany. Theralys Inc, Lyon, France. RP Chabriat, H (reprint author), Hop Lariboisiere, Neurol Serv, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI turton, miranda/F-4682-2011; O'Sullivan, Michael/A-1796-2010; Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 45 TC 62 Z9 69 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 10 PY 2007 VL 69 IS 2 BP 172 EP 179 DI 10.1212/01.wnl.0000265221.05610.70 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 188ER UT WOS:000247902500008 PM 17620550 ER PT J AU Fischl, B Wald, LL AF Fischl, Bruce Wald, Lawrence L. TI Phase maps reveal cortical architecture SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN BRAIN; CORTEX; MR; CONTRAST; VENOGRAPHY; TESLA C1 Massachusetts Gen Hosp, Harvard Med Sch, Athinoula A Martinos Ctr, Dept Radiol, Charlestown, MA 02129 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Comp Sci & Artificial Lab, Cambridge, MA 02139 USA. RP Fischl, B (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [U24 RR021382, P41 RR014075, R01 RR016594, P41-RR14075, R01 RR16594-01A1]; NIBIB NIH HHS [U54 EB005149, R01 EB001550]; NINDS NIH HHS [R01 NS052585, R01 NS052585-01] NR 21 TC 13 Z9 13 U1 0 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 JUL 10 PY 2007 VL 104 IS 28 BP 11513 EP 11514 DI 10.1073/pnas.0704515104 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190MQ UT WOS:000248063400002 PM 17609374 ER PT J AU Kerfoot, BP Holmberg, EF Lawler, EV Krupat, E Conlin, PR AF Kerfoot, B. Price Holmberg, Erika F. Lawler, Elizabeth V. Krupat, Edward Conlin, Paul R. TI Practitioner-level determinants of inappropriate prostate-specific antigen screening SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PRIMARY-CARE PHYSICIANS; ELDERLY-MEN; CANCER; GUIDELINES; QUALITY; CLINICS; GENDER; RATES AB Background: None of the major clinical practice guidelines recommend that prostate-specific antigen (PSA) screening be routinely performed in asymptomatic men older than 75 years or younger than 40 years. We investigated the practitioner-level determinants of inappropriate PSA screening in 7 Veterans Health Administration (VHA) hospitals. Methods: Data on PSA test use from 1997 to 2004 were obtained from VHA databases for 181 139 male patients and the 4823 health care providers who ordered their tests. Patients were excluded from the study population if they underwent PSA testing for nonscreening reasons, as indicated by prostate cancer-specific medications, diagnoses, and procedures. Inappropriate PSA test use was defined as PSA screening in patients older than 75 years or younger than 40 years. Univariate and multivariate Poisson regressions were performed. Results: The mean SD percentage of inappropriate tests by health care provider was 19.3% +/- 15.0%, with 18.4% +/- 14.9% in patients older than 75 years and 0.8% +/- 3.0% in patients younger than 40 years. Practitioners who were urology specialists, male, infrequent PSA test orderers, and affiliated with specific hospitals had significantly higher levels of inappropriate PSA screening. Compared with attending physicians, nurses and physician assistants had significantly lower levels of inappropriate screening. Under multivariate modeling, infrequent PSA test ordering and hospital affiliation retained statistical significance. The percentage of inappropriate PSA screening increased significantly with the age of male health care providers (P < .001). Conclusions: This study elucidates several important provider-level determinants of PSA screening misuse and substantiates that PSA screening is frequently performed counter to evidence-based guidelines. Further work is needed to determine the degree to which "prostatempathy" contributes to PSA misuse by older male providers. C1 VA Boston Healthcare Syst, Surg Serv, Urol Sect, Jamaica Plain, MA 02130 USA. VA Boston Healthcare Syst, Med Serv, Endocrinol Sect, Jamaica Plain, MA 02130 USA. VA Boston Healthcare Syst, Pharmacoepidemiol Res Grp, MAVERIC, Jamaica Plain, MA 02130 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, Surg Serv, Urol Sect, 150 S Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM price.kerfoot@gmail.com FU NHLBI NIH HHS [R01 HL77234]; NIDDK NIH HHS [K24 DK63214] NR 27 TC 23 Z9 23 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 9 PY 2007 VL 167 IS 13 BP 1367 EP 1372 DI 10.1001/archinte.167.13.1367 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 188AT UT WOS:000247891500005 PM 17620529 ER PT J AU Foster, MC Hwang, SJ Larson, MG Parikh, NI Meigs, JB Vasan, RS Wang, TJ Levy, D Fox, CS AF Foster, Meredith C. Hwang, Shih-Jen Larson, Martin G. Parikh, Nisha I. Meigs, James B. Vasan, Ramachandran S. Wang, Thomas J. Levy, Daniel Fox, Caroline S. TI Cross-classification of microalbuminuria and reduced glomerular filtration rate - Associations between cardiovascular disease risk factors and clinical outcomes SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC KIDNEY-DISEASE; CHRONIC RENAL-INSUFFICIENCY; CORONARY HEART-DISEASE; ENDOTHELIAL FUNCTION; SERUM CREATININE; NONDIABETIC INDIVIDUALS; HEMODIALYSIS-PATIENTS; GENERAL-POPULATION; OXIDATIVE STRESS; ALBUMINURIA AB Background: Chronic kidney disease is defined by reduced estimated glomerular filtration rate (reduced eGFR) or by microalbuminuria (MA). Concordance between reduced eGFR and MA and associated cardiovascular disease (CVD) and all-cause mortality according to these definitions is uncertain. Methods: Participants (n = 2966 [52.6% were women], mean age, 59 years) were drawn from the Framingham Offspring Cohort. Participants were classified into 4 groups based on the presence or absence of reduced eGFR (eGFR < 59 mL/min/ 1.73 m(2) in women, < 64 mL/min/ 1.73 m(2) in men or MA (spot urinary albumin to creatinine ratio of at least 30 mg/g). Cox proportional hazard models were used to determine the combined risk of CVD events and all-cause mortality for each group. Results: Of the participants, 9.9% (n = 295) had reduced eGFR, and 12.2% (n = 362) had MA. Among those with reduced eGFR, 28% had MA. Those with reduced eGFR and with MA were at increased risk for combined CVD and all cause mortality compared with those with neither condition (hazard ratio [HR] 1.7, 95% confidence interval [CI], 1.1-2.4; P = .009), whereas those with reduced eGFR and without MA and those without reduced eGFR and with MA had similar HRs (1.3 and 1.2, respectively). Those with reduced eGFR and with MA, as well as those with reduced eGFR and without MA, were at significantly increased risk of all-cause mortality (HR 2.2 [95% CI, 1.4-3.6] and HR 1.7 [95% CI, 1.1-2.6], respectively). Conclusions: Reduced eGFR and MA are relatively common conditions with different risk factor profiles. The coexistence of reduced eGFR and MA was present in 2.8% of the study sample and conferred substantial increased risk for CVD and all-cause mortality, in part because of a heavy burden of CVD risk factors. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, NIH, Framingham, MA 01702 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Gen Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195] NR 45 TC 96 Z9 101 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 9 PY 2007 VL 167 IS 13 BP 1386 EP 1392 DI 10.1001/archinte.167.13.1386 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 188AT UT WOS:000247891500008 PM 17620532 ER PT J AU Baeten, J Niedre, M Dunham, J Ntziachristos, V AF Baeten, John Niedre, Mark Dunham, Joshua Ntziachristos, Vasilis TI Development of fluorescent materials for diffuse fluorescence tomography standards and phantoms SO OPTICS EXPRESS LA English DT Article ID RADIATIVE-TRANSFER; RECONSTRUCTION; EQUATION; LOOKING; MEDIA AB The availability of fluorescence standards is necessary in the development of systems and methods for fluorescence imaging. In this study, two approaches for developing diffuse fluorescence materials to be used as standards or phantoms in diffuse fluorescent tomography applications were investigated. Specifically, silicone rubber and polyester casting resin were used as base materials, and silicone pigments or TiO2/ India Ink were added respectively to vary the optical properties. Characterization of the optical properties achieved was performed using time-resolved methods. Subsequently, different near-infrared fluorochromes were examined for imparting controlled and stable fluorescence properties. It was determined that hydrophobic fluorophores (IR 676 and IR 780 Iodide) suspended in dichloromethane and hydrophilic fluorophores (Cy5.5 and AF 750) suspended in methanol produced diffusive silicone and resin fluorescent materials, respectively. However only the hydrophobic fluorophores embedded within silicone resulted in the construction of a material with the characteristics of a standard, i.e. stability of fluorescence intensity with time and a linear dependence of normalized fluorescence intensity to fluorophore concentration. (c) 2007 Optical Society of America C1 Harvard Univ, Massachusetts Gen Hosp, Mol Imaging Ctr Mol Imaging Res, Lab Bio Opt, Charlestown, MA 02129 USA. Harvard Univ, MIT, Technol Biomed Opt Summer Inst, Div Hlth Sci, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Mol Imaging Ctr Mol Imaging Res, Lab Bio Opt, Boston, MA 02115 USA. RP Baeten, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Mol Imaging Ctr Mol Imaging Res, Lab Bio Opt, CNY149,13th St,5209, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu NR 18 TC 27 Z9 27 U1 1 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUL 9 PY 2007 VL 15 IS 14 BP 8681 EP 8694 DI 10.1364/OE.15.008681 PG 14 WC Optics SC Optics GA 195DY UT WOS:000248393900020 PM 19547203 ER PT J AU Prendergast, A Tudor-Williams, G Jeena, P Burchett, S Goulder, P AF Prendergast, Andrew Tudor-Williams, Gareth Jeena, Prakash Burchett, Sandra Goulder, Philip TI International perspectives, progress, and future challenges of paediatric HIV infection SO LANCET LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-CHILD; ACTIVE ANTIRETROVIRAL THERAPY; PNEUMOCYSTIS-CARINII-PNEUMONIA; RESOURCE-POOR SETTINGS; LATE POSTNATAL TRANSMISSION; POLYMERASE CHAIN-REACTION; MATERNAL VIRAL LOAD; BREAST-FED CHILDREN; HIV-1-INFECTED CHILDREN AB Paediatric HIV infection is a growing health challenge worldwide, with an estimated 1500 new infections every day. in developed countries, well established prevention programmes keep mother-to-child transmission rates at less than 2%. However, in developing countries, where transmission rates are 25-40%, interventions are available to only 5-10% of women. Children with untreated natural infection progress rapidly to disease, especially in resource-poor settings where mortality is greater than 50% by 2 years of age. As in adult infection, antiretroviral therapy has the potential to rewrite the natural history of HIV, but is accessible only to a small number of children needing therapy. We focus on the clinical and immunological features of HIV that are specific to paediatric infection, and the formidable challenges ahead to ensure that all children worldwide have access to interventions that have proved successful in developed countries. C1 Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. Univ London Imperial Coll Sci Technol & Med, Dept Paediat, Div Med, London, England. Univ Kwazulu Natal, Dept Child Life & Hlth, HIV Pathogenesis Programme, Durban, South Africa. Harvard Univ, Sch Med, Div Infect Dis, Childrens Hosp Boston, Boston, MA USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. RP Goulder, P (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. EM philip.goulder@ndm.ox.ac.uk FU Medical Research Council [G0500384]; Wellcome Trust NR 181 TC 67 Z9 69 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUL 7 PY 2007 VL 370 IS 9581 BP 68 EP 80 DI 10.1016/S0140-6736(07)61051-4 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 187QE UT WOS:000247862300032 PM 17617274 ER PT J AU Newhauser, WD Koch, NC Fontenot, JD Rosenthal, SJ Gombos, DS Fitzek, MM Mohan, R AF Newhauser, Wayne D. Koch, Nicholas C. Fontenot, Jonas D. Rosenthal, Stanley J. Gombos, Dan S. Fitzek, Markus M. Mohan, Radhe TI Dosimetric impact of tantalum markers used in the treatment of uveal melanoma with proton beam therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOCHROMIC FILM DOSIMETRY; DOSE-EQUIVALENT EXPOSURES; NONRADIOACTIVE GOLD SEED; MONTE-CARLO SIMULATIONS; IRRADIATION; EYE; RADIOTHERAPY; RADIOGRAPHY; IMPLEMENTATION; ELECTRON AB Metallic fiducial markers are frequently implanted in patients prior to external-beam radiation therapy to facilitate tumor localization. There is little information in the literature, however, about the perturbations in proton absorbed-dose distribution these objects cause. The aim of this study was to assess the dosimetric impact of perturbations caused by 2.5 mm diameter by 0.2 mm thick tantalum fiducial markers when used in proton therapy for treating uveal melanoma. Absorbed dose perturbations were measured using radiochromic film and confirmed by Monte Carlo simulations of the experiment. Additional Monte Carlo simulations were performed to study the effects of range modulation and fiducial placement location on the magnitude of the dose shadow for a representative uveal melanoma treatment. The simulations revealed that the fiducials caused perturbations in the absorbed-dose distribution, including absorbed-dose shadows of 22% to 82% in a typical proton beam for treating uveal melanoma, depending on the marker depth and orientation. The clinical implication of this study is that implanted fiducials may, in certain circumstances, cause dose shadows that could lower the tumor dose and theoretically compromise local tumor control. To avoid this situation, fiducials should be positioned laterally or distally with respect to the target volume. C1 Univ Texas, MD Anderson Canc Ctr, Unit 94, Dept Head & Neck Surg,Sect Ophthalmol, Houston, TX 77030 USA. Univ Texas, Grad Sch Biomed Sci, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Midwest Proton Radiotherapy Inst, Bloomington, IN 47408 USA. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. RP Newhauser, WD (reprint author), Univ Texas, MD Anderson Canc Ctr, Unit 94, Dept Head & Neck Surg,Sect Ophthalmol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM wnewhaus@mdanderson.org RI Grams, Michael/G-5197-2011 NR 56 TC 35 Z9 35 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUL 7 PY 2007 VL 52 IS 13 BP 3979 EP 3990 DI 10.1088/0031-9155/52/13/021 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 175XW UT WOS:000247048300021 PM 17664589 ER PT J AU Leng, YM Cao, C Ren, J Huang, L Chen, DS Ito, M Kufe, D AF Leng, Yumei Cao, Cheng Ren, Jian Huang, Lei Chen, Dongshu Ito, Masaki Kufe, Donald TI Nuclear import of the MUC1-C oncoprotein is mediated by nucleoporin Nup62 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; BETA-CATENIN; APOPTOTIC RESPONSE; GENE-TRANSCRIPTION; SURVIVAL RESPONSE; OXIDATIVE STRESS; TANDEM REPEATS; PROTEIN IMPORT; PORE COMPLEX AB The MUC1 heterodimeric transmembrane protein is aberrantly overexpressed by most human carcinomas. The MUC1 C-terminal subunit (MUC1-C) is devoid of a classical nuclear localization signal and is targeted to the nucleus by an unknown mechanism. The present results demonstrate that MUC1-C associates with importin beta and not importin alpha. The results also show that, like importin beta, MUC1-C binds to Nup62 ( nucleoporin p62). MUC1-C binds directly to the Nup62 central domain and indirectly to the Nup62 C-terminal alpha-helical coiled-coil domain. We demonstrate that MUC1-C forms oligomers and that oligomerization is necessary for binding to Nup62. The MUC1-C cytoplasmic domain contains a CQC motif that when mutated to AQA abrogates oligomerization and binding to Nup62. Stable expression of MUC1 with the CQC -> AQA mutations was associated with targeting to the cell membrane and cytosol and attenuation of nuclear localization. The results further show that expression of MUC1(CQC-AQA) attenuates MUC1-induced (i) transcriptional coactivation, (ii) anchorage-independent growth, and (iii) tumorigenicity. These findings indicate that the MUC1-C oncoprotein is imported to the nucleus by a pathway involving Nup62. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA97098] NR 52 TC 79 Z9 82 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 JUL 6 PY 2007 VL 282 IS 27 BP 19321 EP 19330 DI 10.1074/jbc.M703222200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 184OF UT WOS:000247650600007 PM 17500061 ER PT J AU Christensen, B Kazanecki, CC Petersen, TE Rittling, SR Denhardt, DT Sorensen, ES AF Christensen, Brian Kazanecki, Christian C. Petersen, Torben E. Rittling, Susan R. Denhardt, David T. Sorensen, Esben S. TI Cell type-specific post-translational modifications of mouse osteopontin are associated with different adhesive properties SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID O-GLYCOSYLATION SITES; GLYCINE-ASPARTIC ACID; IN-VITRO; CASEIN KINASE; HYDROXYAPATITE FORMATION; OSTEOCLAST ADHESION; BONE SIALOPROTEIN; MASS-SPECTROMETRY; PHOSPHORYLATION; EXPRESSION AB Osteopontin (OPN) is a highly modified integrin-binding protein found in all body fluids. Expression of OPN is strongly correlated with poor prognosis in many different human cancers, suggesting an important but poorly understood role for this protein in tumorigenesis and metastasis. The protein exists in a number of different isoforms differing in the degree of post-translational modifications that are likely to exhibit different functional properties. This study examines for the first time the post-translational modifications of OPN from transformed cells and the effects of these modifications on cell biology. We have characterized the complete phosphorylation and glycosylation patterns of OPN expressed by murineras-transformed fibroblasts(FbOPN) and differentiating osteoblasts (ObOPN) by a combination of mass spectrometric analyses and Edman degradation. Mass spectrometric analysis showed masses of 34.9 and 35.9 kDa for FbOPN and ObOPN, respectively. Enzymatic dephosphorylation, sequence, and mass analyses demonstrated that FbOPN contains approximately four phosphate groups distributed over 16 potential phosphorylation sites, whereas ObOPN contains similar to 21 phosphate groups distributed over 27 sites. Five residues are O-glycosylated in both isoforms. These residues are fully modified in FbOPN, whereas onesite is partially glycosylated in ObOPN. Although both forms of OPN mediated robust integrin-mediated adhesion of mouse ras-transformed fibroblasts, the less phosphorylated FbOPN mediated binding of MDA-MD-435 human tumor cells almost 6-fold more than the heavy phosphorylated ObOPN. These results strongly support the hypothesis that the degree of phosphorylation of OPN produced by different cell types can regulate its function. C1 Univ Aarhus, Dept Mol Biol, Protein Chem Lab, DK-8000 Aarhus C, Denmark. Rutgers State Univ, Dept Cell Biol & Neurosci, Nelson Labs, Piscataway, NJ USA. Forsyth Inst, Boston, MA USA. RP Sorensen, ES (reprint author), Univ Aarhus, Dept Mol Biol, Protein Chem Lab, Sci Pk,Gustav Wields Vej 10C, DK-8000 Aarhus C, Denmark. EM ess@mb.au.dk FU NIDDK NIH HHS [DK067685] NR 45 TC 88 Z9 94 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2007 VL 282 IS 27 BP 19463 EP 19472 DI 10.1074/jbc.M703055200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 184OF UT WOS:000247650600020 PM 17500062 ER PT J AU Taneja, V Maddelein, ML Talarek, N Saupe, SJ Liebman, SW AF Taneja, Vibha Maddelein, Marie-Lise Talarek, Nicolas Saupe, Sven J. Liebman, Susan W. TI A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast SO MOLECULAR CELL LA English DT Article ID DE-NOVO APPEARANCE; SACCHAROMYCES-CEREVISIAE; IN-VITRO; PSI+ PRION; PODOSPORA-ANSERINA; SUP35 PROTEIN; HETEROKARYON INCOMPATIBILITY; GUANIDINE-HYDROCHLORIDE; HSP104 INACTIVATION; SPECIES BARRIER AB Prions are self-propagating, infectious aggregates of misfolded proteins. The mammalian prion, PrPSc, causes fatal neurodegenerative disorders. Fungi also have prions. While yeast prions depend upon glutamine/asparagine (Q/N)-rich regions, the Podospora anserina HET-s and PrP prion proteins lack such sequences. Nonetheless, we show that the HET-s prion domain fused to GFP propagates as a prion in yeast. Analogously to native yeast prions, transient overexpression of the HET-s fusion induces ring-like aggregates that propagate in daughter cells as cytoplasmically inherited, detergent-resistant dot aggregates. Efficient dot propagation, but not ring formation, is dependent upon the Hsp104 chaperone. The yeast prion [PIN+] enhances HET-s ring formation, suggesting that prions with and without Q/N-rich regions interact. Finally, HET-s aggregates propagated in yeast are infectious when introduced into Podospora. Taken together, these results demonstrate prion propagation in a truly foreign host. Since yeast can host non-Q/N-rich prions, such native yeast prions may exist. C1 Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. Univ Bordeaux 2, CNRS 5095, IBGC, Lab Genet Mol Champignons,UMR, F-33077 Bordeaux, France. Univ Bordeaux 2, CNRS 5095, Heredite Struct Genet Cellulaire, UMR, F-33077 Bordeaux, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Liebman, SW (reprint author), Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. EM suel@uic.edu RI MADDELEIN, Marie-Lise/G-5395-2010; OI saupe, sven/0000-0002-5589-721X FU NIGMS NIH HHS [R01 GM056350, R01 GM056350-10] NR 82 TC 62 Z9 63 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL 6 PY 2007 VL 27 IS 1 BP 67 EP 77 DI 10.1016/j.molcel.2007.05.027 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190VK UT WOS:000248088500007 PM 17612491 ER PT J AU Mason, MF Norton, MI Van Horn, JD Wegner, DM Grafton, ST Macrae, CN AF Mason, Malia F. Norton, Michael I. Van Horn, John D. Wegner, Daniel M. Grafton, Scott T. Macrae, C. Neil TI Response to comment on "Wandering minds: The default network and stimulus-independent thought" SO SCIENCE LA English DT Editorial Material ID CORTEX; TASK; ATTENTION AB Gilbert et al. suggest that activity in the default network may be due to the emergence of stimulus-oriented rather than stimulus-independent thought. Although both kinds of thought likely emerge during familiar tasks, we argue - and report data suggesting - that stimulus-independent thought dominates unconstrained cognitive periods. C1 Harvard Univ, Sch Business, Boston, MA 02163 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. Univ Aberdeen, Sch Psychol, Aberdeen AB24 2UB, Scotland. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Mason, MF (reprint author), Columbia Univ, Uris Hall,3022 Broadway, New York, NY 10027 USA. EM malia.mason@mail.gsb.columbia.edu RI Macrae, Neil/C-4761-2008 NR 15 TC 13 Z9 13 U1 3 U2 12 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 JUL 6 PY 2007 VL 317 IS 5834 BP 43 EP + DI 10.1126/science.1141078 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 186KD UT WOS:000247776700027 ER PT J AU Martin, LF Leonard, S Hall, MH Tregellas, JR Freedman, R Olincy, A AF Martin, Laura F. Leonard, Sherry Hall, Mei-Hua Tregellas, Jason R. Freedman, Robert Olincy, Ann TI Sensory gating and alpha-7 nicotinic receptor gene allelic variants in schizoaffective disorder, bipolar type SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; bipolar disorder; chromosomes; human pair 15; receptors; nicotinic; evoked potentials; auditory ID SUSCEPTIBILITY LOCI; CHROMOSOME 15Q13-14; SUGGESTIVE EVIDENCE; LINKAGE ANALYSIS; NO EVIDENCE; SCHIZOPHRENIA; SCAN; DISEQUILIBRIUM; PEDIGREES; FAMILIES/ AB Objectives: Single nucleotide allelic variants in the promoter region of the chromosome 15 alpha-7 acetylcholine nicotinic receptor gene (CHRNA7) are associated with both schizophrenia and the P50 auditory evoked potential sensory gating deficit. The purpose of this study was to determine if CHRNA7 promoter allelic variants are also associated with abnormal P50 ratios in persons with schizoaffective disorder, bipolar type. Methods: P50 auditory evoked potentials were recorded in a paired stimulus paradigm in 17 subjects with schizoaffective disorder, bipolar type. The P50 test to conditioning ratio was used as the measure of sensory gating. Mutation screening of the CHRNA7 promoter region was performed on the subjects' DNA samples. Comparisons to previously obtained data from persons with schizophrenia and controls were made. Results: Subjects with schizophrenia, regardless of allele status, had an abnormal mean P50 ratio. Subjects with schizoaffective disorder, bipolar type and a variant allele had an abnormal mean P50 ratio, whereas those schizoaffective subjects with the common alleles had a normal mean P50 ratio. Normal control subjects had a normal mean ratio, but controls with variant alleles had higher P50 ratios. Conclusions: In persons with bipolar type schizoaffective disorder, CHRNA7 promoter region allelic variants are linked to the capacity to inhibit the P50 auditory evoked potential and thus are associated with a type of illness genetically and biologically more similar to schizophrenia. (c) 2006 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Martin, LF (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4200 E 9th Ave,C268-71, Denver, CO 80262 USA. EM laura.martin@uchsc.edu RI Tregellas, Jason/J-3637-2015; Hall, Mei-Hua/A-3674-2008 OI Hall, Mei-Hua/0000-0002-4558-7023 FU NIMH NIH HHS [MH 38321, R37 MH038321, R01 MH038321, P50 MH068582, P50 MH068582-030001] NR 27 TC 38 Z9 39 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 5 PY 2007 VL 144B IS 5 BP 611 EP 614 DI 10.1002/ajmg.b.30470 PG 4 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 187QU UT WOS:000247864000005 PM 17192894 ER PT J AU Kumar, P Wu, HQ McBride, JL Jung, KE Kim, MH Davidson, BL Lee, SK Shankar, P Manjunath, N AF Kumar, Priti Wu, Haoquan McBride, Jodi L. Jung, Kyeong-Eun Kim, Moon Hee Davidson, Beverly L. Lee, Sang Kyung Shankar, Premlata Manjunath, N. TI Transvascular delivery of small interfering RNA to the central nervous system SO NATURE LA English DT Article ID CELL-PENETRATING PEPTIDES; INHIBITS TUMOR-GROWTH; IN-VIVO DELIVERY; INTRACELLULAR DELIVERY; MODIFIED SIRNAS; GENE-THERAPY; BRAIN; VIRUS; RECEPTORS; TRANSPORTERS AB A major impediment in the treatment of neurological diseases is the presence of the blood - brain barrier, which precludes the entry of therapeutic molecules from blood to brain. Here we show that a short peptide derived from rabies virus glycoprotein (RVG) enables the transvascular delivery of small interfering RNA ( siRNA) to the brain. This 29-amino-acid peptide specifically binds to the acetylcholine receptor expressed by neuronal cells. To enable siRNA binding, a chimaeric peptide was synthesized by adding nonamer arginine residues at the carboxy terminus of RVG. This RVG-9R peptide was able to bind and transduce siRNA to neuronal cells in vitro, resulting in efficient gene silencing. After intravenous injection into mice, RVG-9R delivered siRNA to the neuronal cells, resulting in specific gene silencing within the brain. Furthermore, intravenous treatment with RVG-9R-bound antiviral siRNA afforded robust protection against fatal viral encephalitis in mice. Repeated administration of RVG-9R-bound siRNA did not induce inflammatory cytokines or anti-peptide antibodies. Thus, RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood - brain barrier. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Iowa, Dept Internal Med, Roy J & Lucille J Carver Coll Med, Iowa City, IA 52242 USA. Samchully Pharm Co Ltd, Res Ctr, Seoul 135735, South Korea. Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. Hanyang Univ, Hanyang Fus Mat Program, Seoul 133791, South Korea. RP Manjunath, N (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM shankar@cbrinstitute.org; swamy@cbrinstitute.org RI Kumar, Priti/C-5699-2009 NR 36 TC 599 Z9 645 U1 16 U2 137 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 5 PY 2007 VL 448 IS 7149 BP 39 EP 43 DI 10.1038/nature05901 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 185OS UT WOS:000247720900032 PM 17572664 ER PT J AU Zhou, PC Porcionatto, M Pilapil, M Chen, YC Choi, Y Tolias, KF Bikoff, JB Hong, EJ Greenberg, ME Segal, RA AF Zhou, Pengcheng Porcionatto, Marimelia Pilapil, Mariecel Chen, Yicheng Choi, Yoojin Tolias, Kimberley F. Bikoff, Jay B. Hong, Elizabeth J. Greenberg, Michael E. Segal, Rosalind A. TI Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors SO NEURON LA English DT Review ID GRANULE CELL-MIGRATION; DEVELOPING CEREBRAL-CORTEX; NEURONAL MIGRATION; NERVOUS-SYSTEM; PHOSPHATIDYLINOSITOL 3-KINASE; NEUROTROPHIN RELEASE; PHOSPHOINOSITIDE 3-KINASE; DIFFERENTIAL EXPRESSION; RADIAL MIGRATION; PROTEIN-KINASE AB During development, neural precursors migrate in response to positional cues such as growth factor gradients. However, the mechanisms that enable precursors to sense and respond to such gradients are poorly understood. Here we show that cerebellar granule cell precursors (GCPs) migrate along a gradient of brain-derived neurotrophic factor (BDNF), and we demonstrate that vesicle trafficking is critical for this chemotactic process. Activation of TrkB, the BDNF receptor, stimulates GCPs to secrete BDNF, thereby amplifying the ambient gradient. The BDNF gradient stimulates endocytosis of TrkB and associated signaling molecules, causing asymmetric accumulation of signaling endosomes at the subcellular location where BDNF concentration is maximal. Thus, regulated BDNF exocytosis; and TrkB endocytosis enable precursors to polarize and migrate in a directed fashion along a shallow BDNF gradient. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, Brazil. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu RI Porcionatto, Marimelia/C-3322-2012 OI Porcionatto, Marimelia/0000-0001-6287-916X FU NICHD NIH HHS [P01 HD18655, P30 HD018655]; NINDS NIH HHS [R01 NS037757-09, NS045500, NS377057, R01 NS037757, R01 NS037757-08, R01 NS045500] NR 101 TC 81 Z9 85 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JUL 5 PY 2007 VL 55 IS 1 BP 53 EP 68 DI 10.1016/j.neuron.2007.05.030 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 189TF UT WOS:000248010700008 PM 17610817 ER PT J AU Nathan, DM AF Nathan, David M. TI Rosiglitazone and cardiotoxicity - Weighing the evidence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COMPLICATIONS; RISK C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. NR 11 TC 68 Z9 69 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 5 PY 2007 VL 357 IS 1 BP 64 EP 66 DI 10.1056/NEJMe078117 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 185OR UT WOS:000247720800013 PM 17551161 ER PT J AU Ulm, JW Perron, M Sodroski, J Mulligan, RC AF Ulm, J. Wesley Perron, Michel Sodroski, Joseph Mulligan, Richard C. TI Complex determinants within the Moloney murine leukemia virus capsid modulate susceptibility of the virus to Fv1 and Ref1-mediated restriction SO VIROLOGY LA English DT Article DE viral restriction; host range; retroviral vector ID FV-1 HOST RANGE; RETROVIRUS RESTRICTION; HUMAN-CELLS; TRIM5-ALPHA; INFECTION; REF1; GENE; RESISTANCE; TROPISM; LV1 AB Two of the most well-known genetic mechanisms in mammalian cells which control the susceptibility of cells to productive infection by retroviruses and lentiviruses rely on the cellular Fv1 and Ref1 restriction factors, which act, after viral entry, to prevent productive infection through their interactions with viral capsid (CA) sequences. While previous studies of Fv1 restriction involving N- and B-tropic murine leukemia viruses (MLVs) had demonstrated that the identity of a single amino acid residue at CA110 (arginine vs. glutamic acid) determines whether the resulting virus is N (arg) or B-tropic (glu), analogous studies of dual-tropic MLVs, such as Moloney MLV (Mo-MLV), have shown that additional residues other than CA110 are also involved in the specification of dual-tropic host range. Here we have further studied the CA determinants of Mo-MLV host range, with an emphasis on identifying additional CA residues and unique combinations of CA residues which differentially influence the ability of the resulting virus to infect murine and human cells. First, we show that CA82, a residue previously identified to affect the pattern of Fv1 restriction of different MLV viruses in murine cells, is a particularly strong potentiator of B-tropism in an Mo-MLV background carrying a glutamic acid residue at CA110 (Al 10E substitution), and that interestingly, different residues at CA82 lead to distinct patterns of restriction in human but not in murine cells. We also identify another CA residue, CA214, as a similarly potent potentiator of B-tropism, in the context of the Al10E substitution. While another substitution at CA110, Al10R, leads to strong potentiation of N-tropism in murine cells, in the absence of additional mutations, we found that A110R alone was not sufficient to confer appreciable restriction in Ref1-expressing cells, despite the fact that authentic N-MLV shows strong restriction in those cells. In conjunction with the A110R substitution, substitutions at CA82, but not at CA214, do lead to significant restriction in human cells, thus demonstrating a distinction between the interactions between those two determinants of restriction and CA110. Finally, using cell lines engineered to express the TRIM5 alpha(hu). gene product, recently identified as the Ref1 restriction factor, and RNAi technology to knock-down expression of TRIM5 alpha(hu). in human cells, we directly demonstrate that the unique patterns of restriction observed in human cells with the different mutants are consistent with a TRIM5 alpha(h mu)-mediated restriction. These studies shed further light on the complex determinants within the viral CA gene product which control the susceptibility of murine and human cells to retroviral infection. (C) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol, AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA USA. RP Mulligan, RC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Genet, 4 Blackfan Circle, Boston, MA 02115 USA. EM mulligan@receptor.med.harvard.edu NR 34 TC 16 Z9 17 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 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2007 VL 363 IS 2 BP 245 EP 255 DI 10.1016/j.virol.2006.09.048 PG 11 WC Virology SC Virology GA 176BQ UT WOS:000247058100001 PM 17343889 ER PT J AU Cronin-Fenton, DP Ries, LA Clegg, LX Edwards, BK AF Cronin-Fenton, Deirdre P. Ries, Lynn A. Clegg, Limin X. Edwards, Brenda K. TI Rising incidence rates of breast carcinoma with micrometastatic lymph node involvement SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HORMONE REPLACEMENT THERAPY; EARLY-STAGE MELANOMA; SENTINEL NODE; CANCER INCIDENCE; MULTICENTER TRIAL; BIOPSY; LYMPHADENECTOMY; DISSECTION; TRENDS; VALIDATION AB We investigated the increased incidence of early-stage breast cancer with micrometastatic lymph node involvement. Breast cancer incidence trends from 1990 through 2002 in the US Surveillance, Epidemiology, and End Results Program catchment area were analyzed. Joinpoint regression was used to show the annual percentage change (APC) in breast cancer incidence trends. The overall incidence of breast cancer among women aged 50-64 years increased 1.8% (95% confidence interval [CI] = 1.4% to 2.2%) per annum from 1990 through 2002 but decreased in all other age groups. Stage IIA and stage IIB tumor incidence increased (APC for stage IIA from 1996 to 2002 = 61.9%, 95% Cl = 51.1% to 73.4%, and APC for stage IIB from 1998 to 2002 = 53.7%, 95% Cl = 20.6% to 96.0%). The incidence of micrometastatic lymph node involvement for stage IIA and stage IIB tumors increased during the 1990s, especially after 1997 (APC = 17.3% for both stages), more for estrogen receptor-positive than estrogen receptor-negative disease. Increased use of mammography screening partly explains the increased incidence of early-stage breast cancer. Increases in small tumors with micrometastatic lymph node involvement may be attributable to the increased use of the sentinel lymph node biopsy in community practice. C1 Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC USA. RP Cronin-Fenton, DP (reprint author), Aarhus Univ Hosp, Dept Clin Epidemiol, Ole Worms Alle 1150, DK-8000 Aarhus, Denmark. EM dc@dce.au.dk NR 48 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 4 PY 2007 VL 99 IS 13 BP 1044 EP 1049 DI 10.1093/jnci/djm026 PG 6 WC Oncology SC Oncology GA 191GF UT WOS:000248118900012 PM 17596573 ER PT J AU MacConaill, LE Aldred, MA Lu, XC LaFramboise, T AF MacConaill, Laura E. Aldred, Micheala A. Lu, Xincheng LaFramboise, Thomas TI Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation SO BMC GENOMICS LA English DT Article ID OLIGONUCLEOTIDE MICROARRAY ANALYSIS; HUMAN GENOME; SEGMENTAL DUPLICATIONS; STRUCTURAL VARIATION; UNIPARENTAL DISOMY; MENTAL-RETARDATION; DELETION; POLYMORPHISM; ARRAYS AB Background: The recent discovery of widespread copy number variation in humans has forced a shift away from the assumption of two copies per locus per cell throughout the autosomal genome. In particular, a SNP site can no longer always be accurately assigned one of three genotypes in an individual. In the presence of copy number variability, the individual may theoretically harbor any number of copies of each of the two SNP alleles. Results: To address this issue, we have developed a method to infer a "generalized genotype" from raw SNP microarray data. Here we apply our approach to data from 48 individuals and uncover thousands of aberrant SNPs, most in regions that were previously unreported as copy number variants. We show that our allele-specific copy numbers follow Mendelian inheritance patterns that would be obscured in the absence of SNP allele information. The interplay between duplication and point mutation in our data shed light on the relative frequencies of these events in human history, showing that at least some of the duplication events were recurrent. Conclusion: This new multi-allelic view of SNPs has a complicated role in disease association studies, and further work will be necessary in order to accurately assess its importance. Software to perform generalized genotyping from SNP array data is freely available online [1]. C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Dana Farber Canc Inst, Boston, MA 02116 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02141 USA. Cleveland Clin, Lerner Res Inst, Genom Med Inst, Cleveland, OH 44195 USA. RP LaFramboise, T (reprint author), Case Western Reserve Univ, Dept Genet, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM laura_macconaill@dfci.harvard.edu; aldredm@ccf.org; xxl16@case.edu; thomas.laframboise@case.edu NR 29 TC 8 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUL 3 PY 2007 VL 8 AR 211 DI 10.1186/1471-2164-8-211 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 196KV UT WOS:000248481200001 PM 17608949 ER PT J AU Aarnoudse, AJLHJ Newton-Cheh, C de Bakker, PIW Straus, SMJM Kors, JA Hofman, A Uitterlinden, AG Witteman, JCM Stricker, BHC AF Aarnoudse, Albert-Jan L. H. J. Newton-Cheh, Christopher de Bakker, Paul I. W. Straus, Sabine M. J. M. Kors, Jan A. Hofman, Albert Uitterlinden, Andre G. Witteman, Jacqueline C. M. Stricker, Bruno H. C. TI Common NOS1AP variants are associated with a prolonged QTc interval in the Rotterdam study SO CIRCULATION LA English DT Article DE arrhythmia; death, sudden; electrocardiography; genetics; long-QT syndrome ID SUDDEN CARDIAC DEATH; NITRIC-OXIDE SYNTHASE; MYOCARDIAL-INFARCTION; HAPLOTYPE RECONSTRUCTION; GENERAL-POPULATION; HEART-FAILURE; RISK-FACTOR; ELECTROCARDIOGRAMS; ARREST; GENOME AB Background - QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was found to be associated with QT-interval variation. We tested for association of 2 NOS1AP variants with QT duration and sudden cardiac death. Methods and Results - The Rotterdam Study is a population-based, prospective cohort study of individuals >= 55 years of age. The NOS1AP variants rs10494366 T > G and rs10918594 C > G were genotyped in 6571 individuals. Heart rate - corrected QT interval ( QTc) was determined with ECG analysis software on up to 3 digital ECGs per individual ( total, 11 108 ECGs from 5374 individuals). The association with QTc duration was estimated with repeated-measures analyses, and the association with sudden cardiac death was estimated by Cox proportional-hazards analyses. The rs10494366 G allele (36% frequency) was associated with a 3.8-ms (95% confidence interval, 3.0 to 4.6; P = 7.8 x 10(-20)) increase in QTc interval duration for each additional allele copy, and the rs10918594 G allele (31% frequency) was associated with a 3.6-ms ( 95% confidence interval, 2.7 to 4.4; P = 6.9 x 10(-17)) increase per additional allele copy. None of the inferred NOS1AP haplotypes showed a stronger effect than the individual single-nucleotide polymorphisms. There were 233 sudden cardiac deaths over 11.9 median years of follow-up. No significant association was observed with sudden cardiac death risk. Conclusions - Common variants in NOS1AP are strongly associated with QT-interval duration in an elderly population. Larger sample sizes are needed to confirm or exclude an effect on sudden cardiac death risk. C1 Erasmus MC, Dept Epidemiol & Biostat, NL-3000 CA Rotterdam, Netherlands. Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. Erasmus MC, Dept Med Informat, NL-3000 CA Rotterdam, Netherlands. Massachusetts Gen Hosp, Dept Biol Mol, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Inspectorate Hlth Care, The Hague, Netherlands. Dutch Med Evaluat Board, The Hague, Netherlands. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol & Biostat, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 FU NHLBI NIH HHS [K23 HL80025] NR 48 TC 90 Z9 95 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 2007 VL 116 IS 1 BP 10 EP 16 DI 10.1161/CIRCULATIONAHA.106.676783 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 185NZ UT WOS:000247719000004 PM 17576865 ER PT J AU Fox, CS Massaro, JM Hoffmann, U Pou, KM Maurovich-Horvat, P Liu, CY Vasan, RS Murabito, JM Meigs, JB Cupples, LA D'Agostino, RB O'Donnell, CJ AF Fox, Caroline S. Massaro, Joseph M. Hoffmann, Udo Pou, Karla M. Maurovich-Horvat, Pal Liu, Chun-Yu Vasan, Ramachandran S. Murabito, Joanne M. Meigs, James B. Cupples, L. Adrienne D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. TI Abdominal visceral and subcutaneous adipose tissue compartments - Association with metabolic risk factors in the Framingham Heart Study SO CIRCULATION LA English DT Article DE abdominal fat; diabetes mellitus; epidemiology; hypertension; intra-abdominal fat; metabolic syndrome X; obesity ID IMPAIRED GLUCOSE-TOLERANCE; ENDOTHELIAL GROWTH-FACTOR; TREATMENT PANEL-III; C-REACTIVE PROTEIN; BETA-CELL FUNCTION; INSULIN-RESISTANCE; JAPANESE-AMERICANS; CARDIOVASCULAR-DISEASE; FAT ACCUMULATION; BODY-FAT AB Background - Visceral adipose tissue ( VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue ( SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Methods and Results - Participants (n = 3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome ( P range < 0.01). In women, relations between VAT and risk factors were consistently stronger than in men. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. For example, among women and men, both SAT and VAT were associated with increased odds of metabolic syndrome. In women, the odds ratio ( OR) of metabolic syndrome per 1 - standard deviation increase in VAT ( OR, 4.7) was stronger than that for SAT ( OR, 3.0; P for difference between SAT and VAT < 0.0001); similar differences were noted for men ( OR for VAT, 4.2; OR for SAT, 2.5). Furthermore, VAT but not SAT contributed significantly to risk factor variation after adjustment for body mass index and waist circumference ( P <= 0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively. Conclusions - Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Div Biostat, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Semmelweis Univ, H-1085 Budapest, Hungary. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Maurovich-Horvat, Pal/0000-0003-0885-736X FU NHLBI NIH HHS [2K24HL04334, N01-HC-25195]; NIDDK NIH HHS [T32 DK007529] NR 75 TC 966 Z9 1007 U1 15 U2 79 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 3 PY 2007 VL 116 IS 1 BP 39 EP 48 DI 10.1161/CIRCULATIONAHA.106.675355 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 185NZ UT WOS:000247719000012 PM 17576866 ER PT J AU Aguilar, D Bozkurt, B Pritchett, A Petersen, NJ Deswal, A AF Aguilar, David Bozkurt, Biykern Pritchett, Allison Petersen, Nancy J. Deswal, Anita TI The impact of thiazolidinedione use on outcomes in ambulatory patients with diabetes mellitus and heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QUALITY-OF-CARE; INSULIN-RESISTANCE; FLUID RETENTION; ROSIGLITAZONE; ASSOCIATION; AGONISTS; THERAPY; COHORT AB Objectives This study sought to examine the relationship between thiazolidinedione (TZD) use and outcomes in ambulatory patients with diabetes and heart failure (HF). Background Thiazolidinediones have been relatively contraindicated in diabetic patients with HF. Methods We conducted a retrospective study of a national cohort of veterans with HF and diabetes treated in ambulatory clinics at Veterans Affairs medical centers. Patients were classified into those using TZDs and those not using insulin-sensitizing medication based on prescriptions filled 90 days before or 30 days after the index outpatient visit. The outcomes were time to hospitalization for HF and time to death. Results Of 7,147 ambulatory HF patients receiving diabetic therapy, 818 (11.4%) were receiving a TZD and 4,700 (65.8%) were not receiving insulin sensitizers. Over 2 years of follow-up, 134 (16.4%) patients receiving TZDs and 741 (15.8%) patients not receiving insulin-sensitizing medications required HF hospitalization (adjusted hazard ratio 1.00, 95% confidence interval 0.81 to 1.24, p = 0.97). A total of 168 (20.5%) patients receiving TZDs and 1,192 (25.4%) patients not receiving insulin-sensitizing medications died (adjusted hazard ratio 0.98, 95% confidence interval 0.81 to 1.17, p = 0.80). Conclusions In ambulatory patients with established HF and diabetes, the use of TZDs was not associated with an increased risk of HF hospitalization or total mortality when compared with those not receiving insulin-sensitizing medications. C1 Baylor Coll Med, Dept Med, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Cardiol Sect, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care Utilizat Studies, Houston, TX USA. RP Aguilar, D (reprint author), Baylor Coll Med, Dept Med, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX 77030 USA. EM daguilar@bcm.edu FU NCRR NIH HHS [5K12RR017665-05] NR 16 TC 26 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 3 PY 2007 VL 50 IS 1 BP 32 EP 36 DI 10.1016/j.jacc.2007.01.096 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 186AD UT WOS:000247750600005 PM 17601542 ER PT J AU Simarro, M Mauger, D Rhee, K Pujana, MA Kedersha, NL Yamasaki, S Cusick, ME Vidal, M Garcia-Blanco, MA Anderson, P AF Simarro, Maria Mauger, David Rhee, Kirsten Pujana, Miguel A. Kedersha, Nancy L. Yamasaki, Satoshi Cusick, Michael E. Vidal, Marc Garcia-Blanco, Mariano A. Anderson, Paul TI Fas-activated serine/threonine phosphoprotein (FAST) is a regulator of alternative splicing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TIA-1; FGFR2; exon definition ID PRE-MESSENGER-RNA; FACTOR RECEPTOR 2; INTRON SEQUENCES; STRESS GRANULES; BINDING-PROTEIN; 5'-SPLICE SITES; EXON; TIA-1; FGFR2; IIIB AB Fas-activated serine/threonine phosphoprotein (FAST) is a survival protein that is tethered to the outer mitochondrial membrane. In cells subjected to environmental stress, FAST moves to stress granules, where it interacts with TIA1 to modulate the process of stress-induced translational silencing. Both FAST and TIAll are also found in the nucleus, where TIA1 promotes the inclusion of exons f lanked by weak splice recognition sites such as exon Illb of the fibroblast growth factor receptor 2 (FGFR2) mRNA. Two-hybrid interaction screens and biochemical analysis reveal that FAST binds to several alternative and constitutive splicing regulators, suggesting that FAST might participate in this process. The finding that FAST is concentrated at nuclear speckles also supports this contention. We show that FAST, like TIA1, promotes the inclusion of exon Illb of the FGFR2 mRNA. Both FAST and TIA1 target a U-rich intronic sequence (IAS1) adjacent the 5' splice site of exon Illb. However, unlike TIA1, FAST does not bind to the IAS1 sequence. Surprisingly, knockdown experiments reveal that FAST and TIA1 act independently of one another to promote the inclusion of exon Illb. Mutational analysis reveals that FAST-mediated alternative splicing is separable from the survival effects of FAST. Our data reveal that nuclear FAST can regulate the splicing of FGFR2 transcripts. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Anderson, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Smith 652,1 Jimmy Fund way, Boston, MA 02115 USA. EM panderson@rics.bwh.harvard.edu RI pujana, Miguel Angel/N-3127-2014; Simarro, Maria/M-3947-2015 OI pujana, Miguel Angel/0000-0003-3222-4044; Simarro, Maria/0000-0001-8917-7328 FU NIAID NIH HHS [AI50167S1, R01 AI050167]; NIAMS NIH HHS [R01 AR51472, R01 AR051472]; NIGMS NIH HHS [R01 GM063090, R01 GM63090] NR 35 TC 18 Z9 18 U1 0 U2 0 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 JUL 3 PY 2007 VL 104 IS 27 BP 11370 EP 11375 DI 10.1073/pnas.0704964104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 188DT UT WOS:000247900000045 PM 17592127 ER PT J AU Araki, KY Sims, JR Bhide, PG AF Araki, Kiyomi Y. Sims, John R. Bhide, Pradeep G. TI Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development SO BRAIN RESEARCH LA English DT Article DE dopamine receptor; striatum; cerebral cortex; ganglionic eminence ID PRECURSOR CELL-PROLIFERATION; MEDIUM SPINY NEURONS; D-3 RECEPTOR; RAT-BRAIN; ANTIPSYCHOTIC-DRUGS; PATTERN-FORMATION; ADENYLYL-CYCLASE; SUBSTANTIA-NIGRA; PRIMARY CULTURES; D1 AB The outcome of dopaminergic signaling and effectiveness of dopaminergic drugs depend on the relative preponderance of each of the five dopamine receptors in a given brain region. The separate contribution of each receptor to overall dopaminergic tone is difficult to establish at a functional level due to lack of receptor subtype specific pharmacological agents. A surrogate for receptor function is receptor protein or mRNA expression. We examined dopamine receptor mRNA expression by quantitative reverse transcription real-time PCR in the striatum, globus pallidus, frontal cortex and cingulate cortex of embryonic and postnatal mice. Samples of each region were collected by laser capture microdissection. D1- and D2-receptor mRNAs were the most abundant in all the regions of the mature brain. The D1-receptor was predominant over the D2-receptor in the frontal and cingulate cortices whereas the situation was reversed in the striatum and globus pallidus. In the proliferative domains of the embryonic forebrain, D3-, D4- and D5-receptors were predominant. In the corpus striatum and cerebral cortex, the D3- and D4-receptors were the only receptors that showed marked developmental regulation. By analyzing D1 receptor protein expression, we show that developmental changes in mRNA expression reliably translate into changes in protein levels, at least for the D1-receptor. (c) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM Bhide@helix.mgh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU NIDA NIH HHS [DA020796, R01 DA020796, R01 DA020796-01A1]; NINDS NIH HHS [NS43426, P30 NS045776, P30 NS045776-04, P30 NS045776-05, P30NS45776, R01 NS043426, R01 NS043426-04, R01 NS043426-05] NR 57 TC 54 Z9 56 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 2 PY 2007 VL 1156 BP 31 EP 45 DI 10.1016/j.brainres.2007.04.043 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 193EL UT WOS:000248257000004 PM 17509542 ER PT J AU DePrimo, SE Bello, CL Smeraglia, J Baum, CM Spinella, D Rini, BI Michaelson, MD Motzer, RJ AF DePrimo, Samuel E. Bello, Carlo L. Smeraglia, John Baum, Charles M. Spinella, Dominic Rini, Brian I. Michaelson, M. Dror Motzer, Robert J. TI Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; ADVANCED COLORECTAL-CANCER; EPITHELIAL OVARIAN-CANCER; MYELOID-LEUKEMIA AML; BREAST-CANCER; PHASE-I; PTK787/ZK-222584 PTK/ZK; BIOLOGICAL-ACTIVITY; ANTITUMOR-ACTIVITY AB Background: Sunitinib malate (SUTENT (R)) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or - intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PIGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3). Methods: Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA. Results: At the end of cycle I, VEGF and PlGF levels increased > 3-fold (relative to baseline) in 24/ 54 (44%) and 22/55 (40%) cases, respectively ( P < 0.001). sVEGFR-2 levels decreased = 30% in 50/ 55 (91%) cases and = 20% in all cases (P < 0.001) during cycle I, while sVEGFR-3 levels were decreased = 30% in 48 of 55 cases ( 87%), and = 20% in all but 2 cases. These levels tended to return to near-baseline after 2 weeks off treatment, indicating that these effects were dependent on drug exposure. Overall, significantly larger changes in VEGF, sVEGFR-2, and sVEGFR-3 levels were observed in patients exhibiting objective tumor response compared with those exhibiting stable disease or disease progression (P < 0.05 for each analyte; analysis not done for PIGF). Conclusion: Sunitinib treatment in advanced RCC patients leads to modulation of plasma levels of circulating proteins involved in VEGF signaling, including soluble forms of two VEGF receptors. This panel of proteins may be of value as biomarkers of the pharmacological and clinical activity of sunitinib in RCC, and of angiogenic processes in cancer and other diseases. C1 Pfizer Global Res & Dev, La Jolla, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP DePrimo, SE (reprint author), Pfizer Global Res & Dev, La Jolla, CA USA. EM sam.deprimo@pfizer.com; carlo.bello@pfizer.com; john.smeraglia@pfizer.com; charles.baum@pfizer.com; dominic.spinella@pfizer.com; rinib2@ccf.org; Dror_Michaelson@dfci.harvard.edu; motzerr@MSKCC.ORG OI Michaelson, Dror/0000-0001-9249-6338 NR 59 TC 215 Z9 223 U1 4 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUL 2 PY 2007 VL 5 AR 32 DI 10.1186/1479-5876-5-32 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 198UD UT WOS:000248652100001 PM 17605814 ER PT J AU Finkbeiner, M Slotnick, SD Moo, LR Caramazza, A AF Finkbeiner, Matthew Slotnick, Scott D. Moo, Lauren R. Caramazza, Alfonso TI Involuntary capture of attention produces domain-specific activation SO NEUROREPORT LA English DT Article DE attentional capture; domain-specific processing; visual word form area ID WORD FORM AREA; PREFRONTAL CORTEX; FUSIFORM GYRUS; VISUAL-SEARCH; TOP-DOWN; FMRI; MEMORY; SPECIALIZATION; MODULATION AB In this study, we ask whether or not the involuntary capture of attention by a specific information type can produce domain-specific activation. Participants indicated the presence of a flicker in rapidly alternating letter-string masks presented in the periphery. Despite letters not being relevant to the task, we found, using functional MRI and a novel task that allowed us to contrast attended and unattended processing of the same visual information, a robust modulation by attentional capture in a localized letter-processing region. This finding suggests that the involuntary capture of attention is sufficient to produce domain-specific activation in early visual processing. C1 Macquarie Univ, Macquarie Ctr Cognit Sci, Sydney, NSW 2121, Australia. Boston Coll, Dept Psychol, Chestnut Hill, MA USA. Massachusetts Gen Hosp, Neurol Dept, Boston, MA USA. Harvard Univ, Cognit Neurosci Lab, Cambridge, MA USA. RP Finkbeiner, M (reprint author), Macquarie Univ, Macquarie Ctr Cognit Sci, Sydney, NSW 2121, Australia. EM matthew.finkbeiner@maccs.mq.edu.au FU NIDCD NIH HHS [K23-DC5068, DC 04542-04] NR 31 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 2 PY 2007 VL 18 IS 10 BP 975 EP 979 DI 10.1097/WNR.0b013e3281668bcc PG 5 WC Neurosciences SC Neurosciences & Neurology GA 184GL UT WOS:000247629000006 PM 17558280 ER PT J AU Kline, JA Hernandez-Nino, J Jones, AE Rose, GA Norton, HJ Camargo, CA AF Kline, Jeffrey A. Hernandez-Nino, Jackeline Jones, Alan E. Rose, Geoffrey A. Norton, H. James Camargo, Carlos A., Jr. TI Prospective study of the clinical features and outcomes of emergency department patients with delayed diagnosis of pulmonary embolism SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE thromboembolism; insurance; liability; malpractice; screening; differential diagnosis; X-ray diagnosis ID CARDIAC TROPONIN-I; RIGHT-VENTRICULAR DYSFUNCTION; BRAIN NATRIURETIC PEPTIDE; DEEP-VEIN THROMBOSIS; NORMOTENSIVE PATIENTS; PROGNOSTIC VALUE; VENOUS THROMBOEMBOLISM; COMPUTED-TOMOGRAPHY; HEPARIN TREATMENT; ULTRASOUND AB Objectives: The authors hypothesized that emergency department (ED) patients with a delayed diagnosis of pulmonary embolism (PE) will have a higher frequency of altered mental status, older age, comorbidity, and worsened outcomes compared with patients who have PE diagnosed by tests ordered in the ED. Methods: For 144 weeks, all patients with PE diagnosed by computed tomographic angiography were prospectively screened to identify ED diagnosis (testing ordered from the ED) versus delayed diagnosis (less than 48 hours postadmission). Serum troponin I level, right ventricular hypokinesis on echocardiography, and percentage pulmonary vascular occlusion were measured at diagnosis; patients were prospectively followed up for adverse events (death, intubation, or circulatory shock). Results: Among 161 patients with PE, 141 (88%) were ED diagnosed and 20 (12%) had a delayed diagnosis. Patients with a delayed diagnosis were older than ED-diagnosed patients (61 [+/- 15] vs. 51 [+/- 17] years; p < 0.001), had a longer median time to heparin administration (33 vs. 8 hours; p < 0.001), and had a higher frequency of altered mental status (30% vs. 8%; p = 0.01) but did not have a higher frequency of prior cardiopulmonary disease (25% vs. 23%). Patients with a delayed diagnosis had equal or worse measures of PE severity (right ventricular hypokinesis on echocardiography, 60% vs. 58%; abnormal troponin I level, 55% vs. 24%); on computed tomographic angiography, ten of 20 patients with a delayed diagnosis had PE in lobar or larger arteries and > 50% vascular obstruction. Patients with a delayed diagnosis had a higher rate of in-hospital adverse events (9% vs. 30%; p = 0.01). Conclusions: In this single-center study, the diagnosis of PE was frequently delayed and outcomes of patients with delayed diagnosis were worse than those of patients with PE diagnosed in the ED. C1 Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. Carolinas Med Ctr, Dept Cardiol, Charlotte, NC 28203 USA. Carolinas Med Ctr, Dept Biostat, Charlotte, NC 28203 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. EM jkline@carolinas.org FU NHLBI NIH HHS [R01 HL074384] NR 33 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 2007 VL 14 IS 7 BP 592 EP 598 DI 10.1197/j.aem.2007.03.1356 PG 7 WC Emergency Medicine SC Emergency Medicine GA 186KB UT WOS:000247776500002 PM 17554011 ER PT J AU Rowe, BH Campbell, SG Boudreaux, ED Colman, I Abu-Laban, RB Sivilotti, MLA Clark, S Camargo, CA AF Rowe, Brian H. Campbell, Sam G. Boudreaux, Edwin D. Colman, Ian Abu-Laban, Riyad B. Sivilotti, Marco L. A. Clark, Sunday Camargo, Carlos A., Jr. TI Community-acquired pneumonia in North American emergency departments: Drug resistance and treatment success with clarithromycin SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE bacterial pneumonia; sputum; microbiological sensitivity tests; pneumonia severity index (PSI); macrolide ID ANTIMICROBIAL RESISTANCE; PNEUMOCOCCAL PNEUMONIA; STREPTOCOCCUS-PNEUMONIAE; BLOOD CULTURES; UNITED-STATES; MANAGEMENT; SURVEILLANCE; GUIDELINES; PATHOGENS; THERAPY AB Background: Limited information on antibiotic resistance of Streptococcus pneumoniae (SP) exists for patients discharged from emergency departments with community-acquired pneumonia. Objectives: Using a standardized collection process, this study examined sputum microbiology in outpatient community-acquired pneumonia. Methods: This was a inulticenter, prospective cohort study conducted in North American emergency departments between December 2001 and May 2003. Thirty-one emergency departments enrolled patients older than 18 years with a Pneumonia Severity Index of I to III. All patients received oral clarithromycin and were followed up for four weeks. SP resistance to macrolides and penicillin was determined by a central laboratory. Results: Among the 317 cultured sputum samples, 116 (37%; 95% confidence interval [CI] = 32% to 42%) grew an identifiable organism; 74 (23% of cultured cases; 95% CI = 19% to 28%) grew non-SP organisms and 42 grew SP organisms (SP positive; 13% of cultured cases; 95% CI = 10% to 17%). A total of 13 resistant organisms (4% of cultured cases; 95% CI = 2% to 6%) were identified. Resistance to macrolides occurred in nine patients (3% of cultured cases [95%, CI = 1% to 5%]; 24% of SP-positive cases [95% CI = 11% to 37%]); and resistance to penicillin occurred in nine patients (3% of all sputum-positive cases [95% CI = 1% to 5%]; 21% of SP-positive cases [95% CI = 9% to 34%]). The four-week cure rates were similar in both groups. Conclusions: Among outpatients with community-acquired pneumonia, half produced adequate sputum samples and most were culture negative. SP resistance was similar to rates from large national databases. C1 Univ Alberta Hosp, Dept Emergency Med, Edmonton, AB T6G 2B7, Canada. Queen Elizabeth Hosp 2, Dept Emergency Med, Halifax, NS, Canada. Cooper Univ Hosp, Dept Emergency Med, Camden, NJ USA. Univ Cambridge, Dept Psychiat, Cambridge, England. Vancouver Gen Hosp, Dept Emergency Med, Vancouver, BC, Canada. Queens Univ, Dept Emergency Med, Kingston, ON, Canada. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Rowe, BH (reprint author), Univ Alberta Hosp, Dept Emergency Med, Edmonton, AB T6G 2B7, Canada. EM brian.rowe@ualberta.ca OI Boudreaux, Edwin/0000-0002-3223-6371 NR 19 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 2007 VL 14 IS 7 BP 607 EP 615 DI 10.1197/j.aem.2007.02.026 PG 9 WC Emergency Medicine SC Emergency Medicine GA 186KB UT WOS:000247776500004 PM 17478882 ER PT J AU Petersen, T Fava, M Alpert, JE Vorono, S Sanders, KM Mischoulon, D AF Petersen, Timothy Fava, Maurizio Alpert, Jonathan E. Vorono, Sienna Sanders, Kathy M. Mischoulon, David TI Does psychiatry residency training reflect the "Real world" of psychiatry practice? A survey of residency graduates SO ACADEMIC PSYCHIATRY LA English DT Article ID PSYCHODYNAMIC PSYCHOTHERAPY; GERIATRIC PSYCHIATRY; MANAGED CARE; PROGRAMS; DEPRESSION; ATTITUDES; HEALTH AB Objective: The authors determine whether Massachusetts General Hospital's residency graduates believed their training reflected their current practice activities. Method: The authors surveyed 134 graduates from MGH and MGH-McLean residency classes from 1983 to 2003. Subjects ranked their satisfaction with different components of training on a scale of 1 to 6 and listed areas they wanted emphasized during residency. Results: Sixty-six subjects (49%) returned surveys. Twenty respondents graduated in the 1980s (Cohort 1), 27 in the 1990s (Cohort 2), and 16 in the 2000s (Cohort 3). The most common activities included psychopharmacology, teaching, supervision, research, administration, psychodynamic therapy, and supportive therapy. Least common activities included geriatrics, addiction, and psychoanalysis. Satisfaction with training was high, as was relevance of training. Conclusions: Our graduates from 1983 to 2003 considered residency good preparation for the world of practice and reported that psychopharmacology should be emphasized during training. Respondents expressed a strong desire for continued training in psychodynamic therapy, despite growing emphasis on short-term therapies and biological treatments. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC-812,15 Parkman St, Boston, MA 02114 USA. EM dmischoulon@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 21 TC 9 Z9 9 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2007 VL 31 IS 4 BP 281 EP 289 DI 10.1176/appi.ap.31.4.281 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 190HI UT WOS:000248049500007 PM 17626190 ER PT J AU Cai, W Holalkere, NS Harris, G Sahani, D Yoshida, H AF Cai, Wenli Holalkere, Nagaraj-Setty Harris, Gordon Sahani, Dushyant Yoshida, Hiroyuki TI Dynamic-threshold level set method for volumetry of porcine kidney in CT images: In vivo and ex vivo assessment of the accuracy of volume measurement SO ACADEMIC RADIOLOGY LA English DT Article DE computerized volumetry; image segmentation; level set; validation; renal volumetry ID COMPUTED-TOMOGRAPHY; TUMOR; SEGMENTATION; LIVER AB Rationale and Objective. We sought to assess the accuracy of a novel computerized volumetry method, called dynamic-thresholding (DT) level set, in determining the renal volume of pigs in CT images on the basis of in vivo and ex vivo reference standards. Methods and Materials. Eight Yorkshire breed anesthetized pigs (weight range 45-50 kg) were scanned on a 64-slice multidetector CT scanner (Sensation 64; Siemens) after injection of an iodinated (300 mg I/ml) contrast agent through an IV cannula. The kidneys of the pigs were then surgically resected and scanned by CT in the same manner. Both in vivo and ex vivo CT images were subjected to our computerized volumetry using DT level set method. The resulting volumes of the kidneys were compared with in vivo and ex vivo reference standards: the former was established by manual contouring of the kidneys on the CT images by an experienced radiologist, and the latter was established as the water displacement volume of the resected kidney. Results. The comparisons of the in vivo and ex vivo measurements by our volumetric scheme with the associated reference standards yielded a mean difference of 1.73 +/- 1.24% and 3.38 +/- 2.51%, respectively. The correlation coefficients were 0.981 and 0.973 for in vivo and ex vivo comparisons, respectively. The mean difference between in vivo and ex vivo reference standards was 5.79 +/- 4.26%, and the correlation coefficient between the two standards was 0.760. Conclusion. Our computerized volumetry using the DT level set method can provide accurate in vivo and ex vivo measurements of kidney volume, despite a large difference between the two reference standards. This technique can be employed in human subjects for the determination of renal volume for preoperative surgical planning and assessment of oncology treatment. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. RP Cai, W (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, 25 New Chardon St 400C, Boston, MA 02114 USA. EM Wenli.Cai@mgh.harvard.edu OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 25 TC 22 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2007 VL 14 IS 7 BP 890 EP 896 DI 10.1016/j.acra.2007.03.005 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 186DP UT WOS:000247759600013 PM 17574138 ER PT J AU Chodosh, J Sultzer, DL Lee, ML Hahn, TJ Reuben, DB Yano, EM Mittman, BS Rubenstein, LZ AF Chodosh, Joshua Sultzer, David L. Lee, Martin L. Hahn, Theodore J. Reuben, David B. Yano, Elizabeth M. Mittman, Brian S. Rubenstein, Laurence Z. TI Memory impairment among primary care veterans SO AGING & MENTAL HEALTH LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc ID COGNITIVE IMPAIRMENT; ELDERLY PERSONS; DEMENTIA; PREVALENCE; DECLINE; QUALITY; SCREEN; HEALTH AB Memory impairment is the most frequent cognitive dysfunction for older patients. Though studies have shown that dementia is often overlooked in primary care settings, there has been minimal focus specifically on memory impairment, on patients' concerns about memory, or their desire to address these concerns. The objectives of this study were to (1) investigate the prevalence of memory impairment among patients without dementia diagnoses, (2) determine the degree of patients' concern about memory impairment and (3) identify other patient characteristics associated with memory impairment among older primary care patients. Using telephone versions of a four-item memory test and proxy-reported cognitive decline for patients unable to complete interviews, we performed memory assessment of randomly selected patients, 75 years and older, without dementia diagnoses who see primary care physicians at least twice every six months. Among 260 patients and 20 proxies, 19.8% had memory impairment at a level indicative of probable dementia. Adjusting for age, ethnicity, and education, subjects who were more concerned about memory impairment were more likely to be impaired. (Adjusted odds ratio [AOR]: 1.4 (for each additional level of concern); 95% confidence interval [Cl]: (1.0-2.0)). Similarly, subjects wanting their physician to discuss with them their memory concerns were more likely to be impaired (AOR: 1.4-95% Cl: 1.0-1.9). Memory impairment is common among older primary care patients without diagnosed dementia. Knowing patients' concerns about memory impairment and their desire to discuss these concerns may facilitate cognitive screening in this setting. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. VA Greater Los Angeles Geriatr Res Educ & Clin Ca, Sepulveda, CA USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Chodosh, J (reprint author), VA Greater Los Angeles Healthcare Syst, 11G 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jchodosh@mednet.ucla.edu OI Mittman, Brian/0000-0003-3589-9178; Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [AG10415] NR 29 TC 4 Z9 4 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD JUL PY 2007 VL 11 IS 4 BP 444 EP 450 DI 10.1080/13607860601086272 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 187ST UT WOS:000247869500010 PM 17612808 ER PT J AU Freedberg, KA Kumarasamy, N Losina, E Cecelia, AJ Scott, CA Divi, N Flanigan, TP Lu, ZG Weinstein, MC Wang, BX Ganesh, AK Bender, MA Mayer, KH Walensky, RP AF Freedberg, Kenneth A. Kumarasamy, Nagalingeswaran Losina, Elena Cecelia, Anitha J. Scott, Callie A. Divi, Nomita Flanigan, Timothy P. Lu, Zhigang Weinstein, Milton C. Wang, Bingxia Ganesh, Aylur K. Bender, Melissa A. Mayer, Kenneth H. Walensky, Rochelle P. CA CEPAC-Int Investigators TI Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy SO AIDS LA English DT Article; Proceedings Paper CT Meeting on Sustaining Treatment Costs - Who Will Pay CY NOV 27-29, 2006 CL Washington, DC SP WHO, UNAIDS, World Bank DE antiretroviral therapy; HIV/AIDS; India ID HIV-INFECTED ADULTS; COTE-DIVOIRE; SOUTHERN INDIA; COTRIMOXAZOLE PROPHYLAXIS; OBSERVATIONAL DATABASE; NATURAL-HISTORY; DISEASE; TRANSMISSION; GUIDELINES; TRIAL AB Background: India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. Objective: To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. Methods: We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/mu l (SD 291 cells/mu l). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-basedregimen. Cost-effectiveness in US dollars peryear of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. Results: Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 < 350cells/mu l, to 88.9 (106.5) months with two lines of therapy initiated at CD4 < 350cells/mu l. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430NLS to US$550NLS as the CD4 starting criterion was increased from CD4 < 250cells/mu l to < 350cells/mu l. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880NLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. Conclusions: In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens. (c) 2007 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Div Gen Med & Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. YR Gaitonde Ctr AIDS Res & Educ, Madras, Tamil Nadu, India. Brown Univ, Miriam Hosp, Providence, RI 02912 USA. RP Freedberg, KA (reprint author), Massachusetts Gen Hosp, Div Gen Med, HIV Res Program, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM kfreedberg@partners.org; kumarasamy@yrgcare.org FU NIAID NIH HHS [U01 AI038858-07, U01 AI038858, U01 AI 38858, T32 AI007433-10, T32 AI007433, T32 AI 07433, R01 AI058736-01A1, R01 AI058736, R01 AI 058736, K25 AI050436-05, K25 AI050436, K25 AI 50436, K24 AI062476-01, K24 AI062476, K24 AI 062476, K23 AI 01794, K23 AI001794, K23 AI001794-05, P30 AI 60354, P30 AI060354, P30 AI060354-03] NR 45 TC 36 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL PY 2007 VL 21 SU 4 BP S117 EP S128 DI 10.1097/01.aids.0000279714.60935.a2 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 210CS UT WOS:000249434900015 PM 17620747 ER PT J AU Durazzo, TC Rothlind, JC Gazdzinski, S Banys, P Meyerhoff, DJ AF Durazzo, Timothy C. Rothlind, Johannes C. Gazdzinski, Stefan Banys, Peter Meyerhoff, Dieter J. TI Chronic smoking is associated with differential neurocognitive recovery in abstinent alcoholic patients: A preliminary investigation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE alcoholism; alcohol dependence; chronic cigarette smoking; neurocognition; recovery ID CHRONIC CIGARETTE-SMOKING; FRONTAL-SUBCORTICAL CIRCUITS; CEREBRAL-BLOOD-FLOW; COGNITIVE PERFORMANCE; NEUROPSYCHIATRIC DISORDERS; FEMALE ALCOHOLICS; STIMULANT ABUSERS; POSTURAL STABILITY; MAJOR DEPRESSION; SOCIAL DRINKERS AB Background: Approximately 50 to 90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests that chronic cigarette smokers show a pattern of neurocognitive dysfunction similar to that observed in alcoholic patients. However, previous studies investigating neurocognitive recovery in abstinent alcoholic patients did not specifically consider the potential effects of chronic cigarette smoking. Methods: This study comprehensively compared longitudinal neurocognitive changes over 6 to 9 months of abstinence among 13 nonsmoking recovering alcoholic patients (ALC) and 12 actively smoking ALC. The neurocognitive performance of the alcoholic groups was compared with nonsmoking light-drinking controls (nonsmoking LD). Results: Nonsmoking ALC exhibited a significantly greater magnitude of longitudinal improvement than smoking ALC on measures of cognitive efficiency, executive skills, visuospatial skills, and working memory. Both nonsmoking ALC and smoking ALC demonstrated equivalent improvement on auditory-verbal learning, auditory-verbal memory, and processing speed. Nonsmoking LD showed no significant changes in neurocognition over time. In cross-sectional comparisons at 6 to 9 months of abstinence, nonsmoking ALC were superior to smoking ALC on measures of auditory-verbal learning, auditory-verbal memory, cognitive efficiency, executive skills, processing speed, and working memory. The longitudinal and cross-sectional neurocognitive differences observed between nonsmoking and smoking ALC remained significant after covarying for group differences in education, estimated premorbid intelligence alcohol consumption, and other potentially confounding variables. In smoking ALC, greater smoking severity was inversely related to longitudinal improvement on multiple neurocognitive measures. Conclusions: These preliminary results suggest that chronic smoking may modulate neurocognitive recovery in abstinent alcoholic patients. More generally, chronic smoking may impact neurocognition in other conditions where is it a prevalent behavior. C1 San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. No Calif Inst Res & Educ, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, 114M,4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU NIAAA NIH HHS [AA10788] NR 122 TC 30 Z9 30 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2007 VL 31 IS 7 BP 1114 EP 1127 DI 10.1111/j.1530-0277.2007.00398.x PG 14 WC Substance Abuse SC Substance Abuse GA 179VO UT WOS:000247318400005 PM 17451399 ER PT J AU Bradley, KA DeBenedetti, AF Volk, RJ Williams, EC Frank, D Kivlahan, DR AF Bradley, Katharine A. DeBenedetti, Anna F. Volk, Robert J. Williams, Emily C. Frank, Danielle Kivlahan, Daniel R. TI AUDIT-C as a brief screen for alcohol misuse in primary care SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol screening; alcohol drinking; primary care ID IDENTIFICATION TEST AUDIT; AT-RISK DRINKING; BEHAVIORAL-COUNSELING INTERVENTIONS; GENERAL-POPULATION SAMPLE; BRIEF PHYSICIAN ADVICE; USE DISORDERS; CONTROLLED-TRIAL; CONSUMPTION; DRINKERS; VETERANS AB Background: The Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questions have been previously validated as a 3-item screen for alcohol misuse and implemented nationwide in Veterans Affairs (VA) outpatient clinics. However, the AUDIT-C's validity and optimal screening threshold(s) in other clinical populations are unknown. Methods: This cross-sectional validation study compared screening questionnaires with standardized interviews in 392 male and 927 female adult outpatients at an academic family practice clinic from 1993 to 1994. The AUDIT-C, full AUDIT, self-reported risky drinking, AUDIT question #3, and an augmented CAGE questionnaire were compared with an interview primary reference standard of alcohol misuse, defined as a Diagnostic and Statistical Manual, 4th ed. alcohol use disorder and/or drinking above recommended limits in the past year. Results: Based on interviews with 92% of eligible patients, 128 (33%) men and 177 (19%) women met the criteria for alcohol misuse. Areas under the receiver operating characteristic curves (AUROCs) for the AUDIT-C were 0.94 (0.91, 0.96) and 0.90 (0.87, 0.93) in men and women, respectively (p=0.04). Based on AUROC curves, the AUDIT-C performed as well as the full AUDIT and significantly better than self-reported risky drinking, AUDIT question #3, or the augmented CAGE questionnaire (p-values < 0.001). The AUDIT-C screening thresholds that simultaneously maximized sensitivity and specificity were >= 4 in men (sensitivity 0.86, specificity 0.89) and >= 3 in women (sensitivity 0.73, specificity 0.91). Conclusions: The AUDIT-C was an effective screening test for alcohol misuse in this primary care sample. Optimal screening thresholds for alcohol misuse among men (>= 4) and women (>= 3) were the same as in previously published VA studies. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM willi@u.washington.edu OI Volk, Robert/0000-0001-8811-5854 FU BHP HRSA HHS [D32-PE16033]; NIAAA NIH HHS [R21 AA14672, R03 AA09496] NR 50 TC 376 Z9 380 U1 7 U2 28 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2007 VL 31 IS 7 BP 1208 EP 1217 DI 10.1111/j.1530-0277.2007.00403.x PG 10 WC Substance Abuse SC Substance Abuse GA 179VO UT WOS:000247318400014 PM 17451397 ER PT J AU Banerji, A Long, AA Camargo, CA AF Banerji, Aleena Long, Aidan A. Camargo, Carlos A., Jr. TI Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: A literature review SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Review DE acute allergic reaction; anaphylaxis; antihistamines; cognitive function; cost; diphenhydramine; impairment; psychomotor performance; sedation; urticaria ID CHRONIC IDIOPATHIC URTICARIA; ENVIRONMENTAL EXPOSURE UNIT; FEXOFENADINE HYDROCHLORIDE 120; EMERGENCY-DEPARTMENT VISITS; HISTAMINE-INDUCED WHEAL; LORATADINE 10 MG; DOUBLE-BLIND; PSYCHOMOTOR PERFORMANCE; 2ND-GENERATION ANTIHISTAMINES; ORAL ANTIHISTAMINES AB First-generation antihistamines can have adverse effects on the central nervous system and thereby complicate discharge planning from the emergency department (ED). Newer antihistamines are potentially safer, causing less sedation with similar efficacy. The aim of this study was to review the literature to better define which antihistamines are good options for the treatment of acute allergic reactions. A Medline search was conducted to identify English language articles published between January 1975 and March 2006 on antihistamines, sedation, and acute allergic reactions. Bibliographies from included studies were further investigated. We focused on sedative potential, effect on cognitive function, efficacy, onset of clinical activity, and cost of antihistamines. Diphenhydramine impairs psychomotor performance and cognitive function. Loratadine and desloratadine are nonsedating but less efficacious than cetirizine orfexofenadine. The incidence of sedation with cetirizine is less than that of first-generation antihistamines but is greater than placebo. Cetirizine has thefastest onset of action among the newer antihistamines. Fexofenadine does not impair psychomotor or cognitive skills and shows no dose-related increase in sedation but has a slower onset of action than diphenhydramine and cetirizine. Newer antihistamines cost similar to$0.52-2.39 more per dose than diphenhydramine ($0.37). Newer antihistamines provide similar efficacy as first-generation antihistamines but with less sedation. We believe this benefit outweighs the small increase in cost and that newer antihistamines should be considered in the management of acute allergic reactions. Although comparative ED-based trials are not available, newer antihistamines are an option for management of acute allergic reactions when sedation is a concern. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Banerji, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, 100 Blossom St,Cox 201, Boston, MA 02114 USA. EM abanerji@partners.org NR 84 TC 23 Z9 24 U1 1 U2 6 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 2007 VL 28 IS 4 BP 418 EP 426 DI 10.2500/aap.2007.28.3015 PG 9 WC Allergy SC Allergy GA 204DV UT WOS:000249024700005 PM 17883909 ER PT J AU Kleinman, RE Murphy, JM Wieneke, KM Desmond, MS Schiff, A Gapinski, JA AF Kleinman, Ronald E. Murphy, J. Michael Wieneke, Kristin M. Desmond, M. Sheila Schiff, Andrew Gapinski, Jennifer A. TI Use of a single-question screening tool to detect hunger in families attending a neighborhood health center SO AMBULATORY PEDIATRICS LA English DT Article DE community health; hunger; screening ID FOOD INSUFFICIENCY; CHILDREN; INCOME; INSECURITY; MODULE AB Objective.-To examine the use and accuracy of a brief screening tool to identify family hunger, administered in an inner-city primary health care setting and the use of food assistance programs by families in this setting, Methods.-Parents were asked to complete a screening tool for hunger during a routine visit with their children to their neighborhood health center. To evaluate the accuracy of the single-question screening, a subsample of parents who completed the screening participated in an extended interview. Patients were from a neighborhood health center in Chelsea, Massachusetts. A total of 1750 families were screened, and 122 parents completed extended interviews. The US Department of Agriculture (USDA) Household Food Security Scale (HFSS) was used as the standard to assess the accuracy of the brief hunger screening tool. The USDA Food Assistance Program Participation Survey was used to gather information about food program use. Results.-The brief hunger screening tool showed 83% sensitivity and 80% specificity (kappa = .62) compared with the HFSS. The screening also had significant time-to-time reliability (77%). Among families screened as hungry, no food assistance programs were fully used. Conclusions.-The single-question screening tool had acceptable sensitivity, specificity, and reliability. Hungry families underused all types of food assistance programs. Taken together, these findings suggest that screening for hunger could become an important addition to routine pediatric health care in low-income neighborhoods. C1 Massachusetts Gen Hosp, Pediat Gastrointestinal & Nutr Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Chelsea Hlth Ctr, Adolescent & Pediat Med Unit, Boston, MA 02114 USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Pediat Gastrointestinal & Nutr Unit, VBK 107,55 Fruit St, Boston, MA 02114 USA. EM rkleinman@partners.org NR 20 TC 24 Z9 24 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JUL-AUG PY 2007 VL 7 IS 4 BP 278 EP 284 DI 10.1016/j.ambp.2007.03.005 PG 7 WC Pediatrics SC Pediatrics GA 196SA UT WOS:000248501100005 PM 17660098 ER PT J AU Mansbach, JM Pelletier, AJ Camargo, CA AF Mansbach, Jonathan M. Pelletier, Andrea J. Camargo, Carlos A., Jr. TI US outpatient office visits for bronchiolitis, 1993-2004 SO AMBULATORY PEDIATRICS LA English DT Article DE bronchiolitis; primary care; variation in care ID RESPIRATORY SYNCYTIAL VIRUS; EMERGENCY-DEPARTMENTS; AMBULATORY CHILDREN; CONTROLLED-TRIAL; MANAGEMENT; INFECTION; INFANTS; HOSPITALIZATIONS; PREDNISOLONE; EPINEPHRINE AB Objective.-To describe the clinical epidemiology of US outpatient visits for children younger than 2 years with bronchiolitis. Methods.-Data were obtained from the 1993-2004 National Ambulatory Medical Care Survey. Visits had ICD-9 code 466 and were restricted to patients younger than 2 years. National estimates were obtained by using assigned patient visit weights and reported with 95% confidence intervals (95% Cls) calculated by the relative standard error of the estimate; analysis included the X-2 test. Results.-From 1993 to 2004, bronchiolitis accounted for approximately 198 outpatient visits representing 8.75 million visits for children younger than 2 years. Among this same age group, the overall rate was 103 (95% Cl 83, 124) per 1000 US children and 17 (95% CI, 13, 20) per 1000 visits. When we compared bronchiolitis visits to all nonbronchiolitis visits, we found that those with bronchiolitis were less likely to be from the Northeast (12% vs 22%; P < .05) and more likely to be admitted to the hospital (2% vs 0.4%; P < .05). Fifty-two percent were prescribed albuterol; diagnostic tests were uncommon. Conclusions.-The annual number of outpatient office visits for bronchiolitis among children younger than 2 years has remained stable over the last decade but has averaged almost 750 000 visits per year. More than half of primary care providers are prescribing medications to children with bronchiolitis. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Mansbach, JM (reprint author), Childrens Hosp, Dept Med, Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 25 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JUL-AUG PY 2007 VL 7 IS 4 BP 304 EP 307 DI 10.1016/j.ambp.2007.03.006 PG 4 WC Pediatrics SC Pediatrics GA 196SA UT WOS:000248501100009 PM 17660102 ER PT J AU Steinberg, BA Moghbeli, N Buros, J Ruda, M Parkhomenko, A Raju, BS Garcia-Castillo, A Janion, M Nicolau, JC Fox, KAA Morrow, DA Gibson, CM Antman, EM AF Steinberg, Benjamin A. Moghbeli, Nazanin Buros, Jacqueline Ruda, Mikhail Parkhomenko, Alexander Raju, B. Sorna Garcia-Castillo, Armando Janion, Marianna Nicolau, Jose C. Fox, Keith A. A. Morrow, David A. Gibson, C. Michael Antman, Elliott M. TI Acute ischemic heart disease - Global outcomes of ST-elevation myocardial infarction: Comparisons of the enoxaparin and thrombolysis reperfusion for acute myocardial infarction treatment-thrombolysis in myocardial infarction study 25 (ExTRACT-TIMI 25) registry and trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROME; SIMPLE RISK INDEX; UNITED-STATES; UNFRACTIONATED HEPARIN; RANDOMIZED-TRIALS; CLINICAL-TRIAL; MANAGEMENT; FIBRINOLYSIS; MORTALITY; PATIENT AB Background Outcomes in patients with ST-elevation myocardial infarction (STEMI) differ between those in clinical trials and those in routine practice, as well as across different regions. We hypothesized that adjustment for baseline risk would minimize such variations. Methods The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction (ExTRACT-TIMI) 25 registry was an observational study of patients with STEMI presenting to hospitals participating in the ExTRACT-TIMI 25 randomized clinical trial. Consecutive patients with STEMI who were not enrolled in the trial were entered into the registry. Demographics, in-hospital therapies, and in-hospital events were collected. Baseline risk was assessed using the TIMI Risk Index for STEMI. To adjust for differences among the countries from which the patients presented, the gross national income per annum per capita (GNI) was used. Results A total of 3726 patients were registered from 109 sites in 25 countries. Patients in the registry had a higher baseline risk than those in the trial; they had more extensive prior cardiac histories and more comorbidities. Unadjusted in-hospital mortality was higher in the registry (8.3%) than in the trial (6.6%) (hazard ratio, 1.30; P <.00 1); however, after adjusting for TIMI Risk Index, mortality was similar (hazard ratio(adj) 1.00; P =.97). The GNI was not significantly predictive of in-hospital mortality in the multivariable model of the registry. Conclusion Patients in the registry had higher mortality than those in the trial. This difference could be explained by the higher baseline risk of patients in the registry. After adjusting for baseline risk, the GNI of the country in which the patient presented did not contribute to predicting in-hospital mortality. C1 TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Natl Inst Cardiol, Warsaw, Poland. Inst Cardiol, Kiev, Ukraine. Care Hosp, Hyderabad, Andhra Pradesh, India. Hosp Enfermedades Cardiovasc & Torax, Monterrey, Mexico. Swietokrzyskie Ctr Kardiol, Kielce, Poland. Univ Sao Paulo, Sch Med, Inst Heart, BR-05508 Sao Paulo, Brazil. Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. RP Steinberg, BA (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM eantmon@rics.bwh.harvard.edu RI Nicolau, Jose/E-1487-2012; OI Buros, Jacqueline/0000-0001-9588-4889 NR 21 TC 10 Z9 12 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 JUL PY 2007 VL 154 IS 1 BP 54 EP 60 DI 10.1016/j.ahj.2007.03.047 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 188KR UT WOS:000247919300008 PM 17584551 ER PT J AU Joy, T Grinspoon, SK AF Joy, Tisha Grinspoon, Steven K. TI Adipose compartmentalization and insulin resistance among obese HIV-infected women: the role of intermuscular adipose tissue SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID ABDOMINAL FAT; LIPODYSTROPHY; ASSOCIATION; GLUCOSE; RISK C1 Massachusetts Gen Hosp, Program Nutr Metabolism, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metabolism, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 12 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2007 VL 86 IS 1 BP 5 EP 6 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 189IF UT WOS:000247981900003 PM 17616756 ER PT J AU Nolt, BR Gonzales, R Maselli, J Aagaard, E Camargo, CA Metlay, JP AF Nolt, Brendon R. Gonzales, Ralph Maselli, Judy Aagaard, Eva Camargo, Carlos A., Jr. Metlay, Joshua P. TI Vital-sign abnormalities as predictors of pneumonia in adults with acute cough illness SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; ANTIMICROBIAL THERAPY; DIAGNOSING PNEUMONIA; PHYSICAL-EXAMINATION; CLINICAL-PREDICTION; MANAGEMENT; OUTCOMES; OUTPATIENTS; QUALITY; RISK AB Purpose: This study examines the strength of the association between vital-sign abnormalities, advanced age, and the diagnosis of community-acquired pneumonia (CAP) in the evaluation of adults with acute cough illness. Methods: A random sample of adult visits for acute cough to 15 EDs during the winter period of 2 consecutive years (2003-2005) was selected for medical record abstraction. Visits were initially sampled based on discharge diagnoses for a broad range of acute respiratory tract infection diagnoses. Participating sites were a national sample of EDs in Veterans Administration and non-Veterans Administration hospitals stratified across the US region. Results: Of 4464 charts reviewed, 421 had a diagnosis of CAP based on physician discharge diagnosis and radiographic findings. Age greater than 50 years and vital-sign abnormality (including fever, hypoxemia, tachycardia, or tachypnea) were the only significant predictors of CAP. Hypoxemia had the strongest association with CAP diagnosis (odds ratio, 3.5; 95% confidence interval, 2.4-5.0). A greater number of abnormalities were associated with a higher prevalence of CAP, from 12% with 1 abnormality to 69% with 4 vital-sign abnormalities (P <.001). Most vital-sign abnormalities were predictive of CAP regardless of age. Conclusions: Increases in vital-sign abnormalities are associated with a greater probability of CAP, and the strength of the association does not vary substantially by age. (c) 2007 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Metlay, JP (reprint author), VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. EM jmetlay@cceb.med.upenn.edu FU AHRQ HHS [1 R01 HS013915] NR 20 TC 11 Z9 12 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2007 VL 25 IS 6 BP 631 EP 636 DI 10.1016/j.ajem.2006.11.031 PG 6 WC Emergency Medicine SC Emergency Medicine GA 189WS UT WOS:000248019900008 PM 17606087 ER PT J AU Linnan, L Weiner, B Graham, A Emmons, K AF Linnan, Laura Weiner, Bryan Graham, Amanda Emmons, Karen TI Manager beliefs regarding worksite health promotion: Findings from the Working Healthy Project 2 SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Worksite Health Promotion; management; organizational change; worksite interventions ID PROGRAMS; PARTICIPATION AB Purpose. To explore differences in manager beliefs about worksite health promotion programs (HPP). Design. Cross-sectional written survey. Setting. Twenty-four manufacturing worksites, with 11,811 employees and 1719 eligible managers. Subjects. Sixty-six percent (1133/1719) of managers completed the survey; 1047 managers were categorized by level (169 senior 567 middle, and 311 line supervisors). Analysis. Results are reported on overall manager beliefs (and by manager level) about importance, efficacy, barriers, and benefits of HPPs. Multilevel analysis modeled the influence of manager level, age, and experience with HHPs on beliefs about HPPs, while accounting for worksite-level effects. Results. Seventy-five percent of managers beleived that offering HPPs is highly important. Eighty percent beleived that HPPs improved employee health, 68% believed that they reduced health care costs, and 67% believed that they improved employee morale. Few significant differences by manager level were observed on the perceived importance of health promotion, employer responsibilities for health promotion and protection, and efficacy of health promotion strategies or perceived benefits. Senior managers (vs. line supervisors) were significantly less likely to beleive that space or cost was a barrier to offering HPPs and were less likely than middle managers or line supervisors to believe that production conflicts were barriers to offering HPPs. Conclusion. Targeted interventions to address managers beliefs, including differences by age, experience, and manager level, are worth consideration when planning worksite HPPs. (Am J Health Promot 2007;21[6]:521-528.) C1 Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Hlth Policy & Adm, Chapel Hill, NC 27515 USA. Miriam Hosp, Providence, RI 02906 USA. Ctr Behav & Prevent Med, Providence, RI 02906 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Linnan, L (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, CB 7440, Chapel Hill, NC 27599 USA. EM linnan@email.unc.edu FU NCI NIH HHS [P01 CA50087] NR 14 TC 21 Z9 21 U1 2 U2 7 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JUL-AUG PY 2007 VL 21 IS 6 BP 521 EP 528 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 188AQ UT WOS:000247891200009 PM 17674640 ER PT J AU Lin, JP O'Donnell, CJ Jin, L Fox, C Yang, Q Cupples, LA AF Lin, Jing-Ping O'Donnell, Christopher J. Jin, Li Fox, Caroline Yang, Qiong Cupples, L. Adrienne TI Evidence for linkage of red blood cell size and count: Genome-wide scans in the Framingham Heart Study SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE red blood cell; mean corpuscular volume; mean corpuscular hemoglobin; genome scan; linkage ID ERYTHROPOIETIN RECEPTOR GENE; KRUPPEL-LIKE FACTOR; BETA-GLOBIN GENE; TRANSCRIPTION FACTOR; TRAIT LOCI; EKLF; HEMATOCRIT; MUTATION; ELEMENT; RISK AB Red blood cell (RBC) count and size are major criteria for evaluating anemia and related hematology disease diagnoses. While environmental factors influence RBC count (RBCC) and size, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), studies have indicated that each of these measures has a substantial genetic component. So far, no linkage analysis or genome scan has been reported. We carried out 10 cM genome-wide scans on RBCC, MCV, and MCH in a community-based Caucasian cohort, the Framingham Heart Study, using 325 pedigrees with 1,144 individuals genotyped and phenotyped. Using variance-component linkage methods, heritabilities were estimated as 56, 52, and 52% after covariate adjusted for RBCC, MCV, and IVICH, respectively. For RBCC, we found a maximum LOD score of 3.2 on chromosome 19, 24 cM (7.0 Mbp). Near this region, there lie a few important candidate genes, including erythropoietin receptor and erythroid Kruppel-like factor. For linkage analyses for MCV and IVICH, there were coinciding maximized LOD scores on chromosome 11, 9 cM (5.2 Mbp) with values of 3.8 and 3.6, respectively. Under the peak resides the hemoglobin beta cluster - several beta-like genes, which are important candidates for RBC size. In subsequent analyses, we excluded individuals with low MCV to assess the possible influence of beta-thalassemia carriers, and there continued to be evidence for linkage in the same region on chromosome 11p15 (LOD scores of 2.6 and 2.7 for MCV and IVICH, respectively). For MCV, we also identified a new region on chromosome 6q24 with a LOD score of 2.9. These findings suggest that further studies are warranted to identify potential causal genetic variants for RBC size and count and related erythrocyte indices. C1 NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NHLBI, Framingham Heart Study, Off Director, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Cincinnati, Ctr Genom Informat, Cincinnati, OH USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Lin, JP (reprint author), NHLBI, Off Biostat Res, NIH, 6701 Rockledge Dr Suite 8110, Bethesda, MD 20892 USA. EM linj@nhlbi.nih.gov RI Jin, Li/C-1468-2009; Yang, Qiong/G-5438-2014; OI Jin, Li/0000-0002-4546-2415; Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [N01 HC25195] NR 31 TC 24 Z9 24 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2007 VL 82 IS 7 BP 605 EP 610 DI 10.1002/ajh.20868 PG 6 WC Hematology SC Hematology GA 183EO UT WOS:000247555700001 PM 17211848 ER PT J AU Masiello, D Heeney, MM Adewoye, AH Eung, SH Luo, HY Steinberg, MH Chui, DHK AF Masiello, David Heeney, Matthew M. Adewoye, Adebore H. Eung, Shawn H. Luo, Hong-Yuan Steinberg, Martin H. Chui, David. H. K. TI Hemoglobin SE disease - A concise review SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Review DE sickle cell disease; variant hemoglobin; beta-thalassemia ID SICKLE-CELL-DISEASE; E-GLOBIN GENE; E HBSE DISEASE; BETA-THALASSEMIA; CELL/BETA-THALASSEMIA; CLINICAL SEVERITY; MULTIPLE ORIGINS; HYDROXYUREA; MUTATION; ANEMIA AB An infant with Hb SE disease is reported. He was clinically well. Review of the literature shows that patients aged 18 and younger are usually well. On the other hand, more than half of those aged 20 and older developed sickling-related complications, including potentially life-threatening acute chest syndrome. These patients have 60-65% Hb S, similar to the percent Hb S in patients with Hb S/beta(+)-thalassemia. Their hematological features and clinical course appear to parallel those of Hb S/beta(+)-thalassemia. Patients have variable levels of anemia, and some develop clinical complications. With population migrations and increasing racial intermarriages, Hb SE disease is expected to be encountered more often around the globe. Patients with Hb SE disease should be followed and managed in a similar fashion as those with Hb S/beta(+)-thalassemia, and treated appropriately when they develop sickling-related symptoms and complications. C1 Boston Med Ctr, Hemoglobin Diagnost Reference Lab, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Ctr Excellence Sickle Cell Dis, Boston, MA 02118 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. RP Chui, DHK (reprint author), Boston Med Ctr, Hemoglobin Diagnost Reference Lab, Evans 248,88 E Newton St, Boston, MA 02118 USA. EM david.chui@bmc.org RI Heeney, Matthew/J-6838-2015; OI Heeney, Matthew/0000-0002-1104-6843; Steinberg, Martin/0000-0001-8800-8020 FU NHLBI NIH HHS [1 U54 HL708819]; NIDDK NIH HHS [R01 DK069646] NR 44 TC 15 Z9 15 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2007 VL 82 IS 7 BP 643 EP 649 DI 10.1002/ajh.20847 PG 7 WC Hematology SC Hematology GA 183EO UT WOS:000247555700009 PM 17278112 ER PT J AU de Boer, IH Ioannou, GN Kestenbaum, B Brunzell, JD Weiss, NS AF de Boer, Ian H. Ioannou, George N. Kestenbaum, Bryan Brunzell, John D. Weiss, Noel S. TI 25-hydroxyvitamin D levels and albuminuria in the Third National Health and Nutrition Examination Survey (NHANES III) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE vitamin D; albuminuria; microalbuminuria; kidney; epidemiology ID RENIN-ANGIOTENSIN SYSTEM; CHRONIC KIDNEY-DISEASE; NEGATIVE ENDOCRINE REGULATOR; VITAMIN-D; NEPHROTIC SYNDROME; SERUM 25-HYDROXYVITAMIN-D; 1,25-DIHYDROXYVITAMIN D-3; ALBUMIN/CREATININE RATIO; NONDIABETIC INDIVIDUALS; CARDIOVASCULAR EVENTS AB Background: Albuminuria is a risk factor for chronic kidney disease progression, end-stage renal disease, cardiovascular events, and mortality. Animal studies suggested that vitamin D insufficiency may contribute to the pathogenesis of albuminuria. Study Design: Cross-sectional study. Setting & Participants: 15,068 adults participating in the Third National Health and Nutrition Examination Survey. Predictor: Serum 25-hydroxyvitamin D concentration, examined in quartiles. Outcomes & Measurements: Albuminuria, defined using established sex-specific cutoff values for urine albumin-creatinine ratio (25 to 2,999 mg/g for women, 17 to 2,999 mg/g for men). Results: A stepwise increase in the prevalence of albuminuria was observed with decreasing quartiles of vitamin D concentration: 8.9%, 11.5%, 13.7%, and 15.8% (P < 0.001). Adjusting for age, sex, race/ethnicity, region and season of measurement, smoking status, body mass index, and estimated glomerular filtration rate, relative risks for albuminuria by decreasing quartile of vitamin D concentration were 1.00 (reference group), 1.14 (95% confidence interval, 0.95 to 1.37), 1.22 (95% confidence interval, 1.03 to 1.45), and 1.37 (95% confidence interval, 1.10 to 1.71; P = 0.006). Additionally adjusting for blood pressure and diabetes mellitus, these risks were somewhat attenuated and retained statistical significance. Limitations: The cross-sectional design of this study does not allow demonstration of temporal or causal relationships between vitamin D and albuminuria. Conclusions: Additional studies are needed to clarify the relationship of vitamin D with albuminuria and determine whether vitamin D therapy prevents or improves markers of kidney and cardiovascular disease. C1 Univ Washington, Div Nephrol, Seattle, WA 98117 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP de Boer, IH (reprint author), Univ Washington, Div Nephrol, Box 356521,1959 NE Pacific, Seattle, WA 98117 USA. EM deboer@u.washington.edu FU NCRR NIH HHS [5 K12 RR023265-03] NR 50 TC 150 Z9 153 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2007 VL 50 IS 1 BP 69 EP 77 DI 10.1053/j.ajkd.2007.04.015 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 197QJ UT WOS:000248570400009 PM 17591526 ER PT J AU Gripp, KW Lin, AE Nicholson, L Allen, W Cramer, A Jones, KL Kutz, W Peck, D Rebolledo, MA Wheeler, PG Wilson, W Al-Rahawan, MM Stabley, DL Sol-Church, K AF Gripp, Karen W. Lin, Angela E. Nicholson, Linda Allen, William Cramer, Andrea Jones, Kenneth L. Kutz, Wendy Peck, Dawn Rebolledo, Michael A. Wheeler, Patricia G. Wilson, William Al-Rahawan, Mohamad M. Stabley, Deborah L. Sol-Church, Katia TI Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE VMA; HVA; hypertrophic cardiomyopathy; pulmonic stenosis; ras/MAPK pathway ID HRAS MUTATIONS; ABNORMALITIES; GENOTYPE; PATHWAY; ORIGIN; KRAS AB Because Cardio-facio-cutaneous (CFC) syndrome has significant phenotypic overlap with Costello syndrome, it may be difficult to establish the diagnosis on a clinical basis. The recent discoveries of germline HRAS mutations in patients with Costello syndrome and mutations in BRAF, MEK1, and MEK2 in CFC syndrome uncovered the biologic mechanism for the shared phenotypic findings based on the close interaction of the affected gene products within the MAP kinase pathway. We evaluated a series of patients who were either clinically diagnosed with Costello syndrome, or in whom the diagnoses of both Costello and CFC syndromes were considered. After excluding mutations in HRAS, we identified eight changes in BRAF and five in MEK1. Five mutations are novel, and all changes occurred de novo among those triads tested. A review of the clinical abnormalities showed important differences between patients with either a BRAF or MEK1 mutation, and those previously reported with an HRAS mutation. Statistical significance was achieved, despite the relatively small number of patients with BRAF and MEK1 mutations reported here, for polyhydramnios, growth hormone deficiency and the presence of more than one papilloma, which were less common in CFC compared to HRAS mutation positive patients. Although both CFC and Costello syndrome are characterized by cardiac abnormalities in about three-fourths of patients, the pattern of congenital heart defects (CHD), hypertrophic cardiomyopathy (HCM), and tachycardia differs somewhat. CHD, especially pulmonic stenosis associated with a secundum-type atrial septal defect, are more common in CFC than Costello syndrome (P = 0.02). Atrial tachycardia is less frequent in CFC patients with BRAF or MEK1 mutations, compared to Costello syndrome patients with HRAS mutation (P = 0.04). Chaotic atrial rhythm or multifocal atrial tachycardia was observed only in Costello syndrome. Malignant tumors have been viewed as characteristic for Costello syndrome due to HRAS mutations, however, we report here on a MEK1 mutation in a patient with a malignant tumor, a hepatoblastoma. Although this indicates that the presence of a tumor is not specific for Costello syndrome with HRAS mutation, it is noteworthy that the tumor histology differs from those commonly seen in Costello syndrome. Based on these clinical differences we suggest that patients with BRAF and MEK mutations should be diagnosed with CFC syndrome, and the diagnosis of Costello syndrome be reserved for patients with HRAS mutations. (c) 2007 Wiley-Liss, Inc. C1 Alfred I DuPont Hosp Children, Div Med Genet, Nemours Childrens Clin, Wilmington, DE 19899 USA. Massachusetts Gen Hosp, Genet Unit, Boston, MA 02114 USA. Mission Hosp, Fullerton Genet Ctr, Asheville, NC USA. Presbyterian Med Ctr, Dept Pediat, Dallas, TX USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Alfred I DuPont Hosp Children, Div Dermatol, Nemours Childrens Clin, Wilmington, DE 19899 USA. Univ Missouri, Sch Med, Div Med Genet, Dept Child Hlth, Columbia, MO USA. Childrens Hosp Orange Cty, Inst Heart, Orange, CA 92668 USA. Nemours Childrens Clin, Div Genet & Metab, Orlando, FL USA. Univ Virginia Hlth Syst, Dept Pediat, Charlottesville, VA USA. Alfred I DuPont Hosp Children, Dept Biomed Res, Nemours Childrens Clin, Wilmington, DE 19899 USA. RP Gripp, KW (reprint author), Alfred I DuPont Hosp Children, Div Med Genet, Nemours Childrens Clin, POB 269, Wilmington, DE 19899 USA. EM kgripp@nemours.org FU NCRR NIH HHS [P30 RR 020173-01] NR 19 TC 48 Z9 54 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL 1 PY 2007 VL 143A IS 13 BP 1472 EP 1480 DI 10.1002/ajmg.a.31815 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 186DZ UT WOS:000247760600010 PM 17551924 ER PT J AU Leach, NT Chudoba, I Stewart, TV Holmes, LB Weremowicz, S AF Leach, Natalia T. Chudoba, Ilse Stewart, Tasheena V. Holmes, Lewis B. Weremowicz, Stanislawa TI Maternally inherited duplication of chromosome 7, dup(7)(p11.2p12), associated with mild cognitive deficit without features of Silver-Russell syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE duplication; chromosome 7; fluorescence in situ hybridization (FISH); multicolor banding (mBAND); Silver-Russell syndrome (SRS) ID DIRECT TANDEM DUPLICATION; CANDIDATE GENE REGION; UNIPARENTAL DISOMY 7; HUMAN GRB10; INCLUDING GRB10; TRISOMY 7P; SHORT ARM; PHENOTYPE; SEGMENT; ABERRATIONS AB We report on a familial duplication in the short arm of chromosome 7, dup(7)(p11.2p12, present in three generations The duplication was identified by GTG-banding and fluorescence in situ hybridization (FISH) with a whole chromosome 7 DNA painting probe that verified that the duplicated material originated from chromosome 7. The multicolor banding (mBAND) was used to refine the breakpoint assignment. The duplication identified in the proband was also present in her son and mother. All three carriers have mild cognitive deficiencies. Interstitial duplications of the short arm of chromosome 7, although relatively uncommon, have been described in association with a variety of clinical features, including mental retardation of varying severity. Duplication of the p11.2p13 region on chromosome 7 was reported in association with Silver-Russell syndrome (SRS), and an overlapping dup(7) (p11.2.p14.1)dn was described in an individual with autistic disorder. Furthermore, a potentially overlapping maternally transmitted inverted duplication, dup(7)(p13p12.2), was reported in patients with cognitive delay. These observations and the phenotype of our duplication carriers suggest that partial trisomy of the proximal 7p region causes cognitive deficiency. The maternal origin of the duplication is of special interest in light of genomic imprinting and implication of the 7p11-p13 region in the SRS etiology. Locus-specific FISH targeting a growth factor receptor binding protein 10 (GRB10), the strong candidate for SRS residing at 7p.12.2, showed that it is not duplicated in our patients. Our study helps refine the SRS critical region on 7p and extends our Understanding of the clinical manifestations associated with 7p duplications. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. MetaSystems, Altlussheim, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Leach, NT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM leach@rics.bwh.harvard.edu NR 33 TC 14 Z9 15 U1 1 U2 3 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 JUL 1 PY 2007 VL 143A IS 13 BP 1489 EP 1493 DI 10.1002/ajmg.a.31794 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 186DZ UT WOS:000247760600012 PM 17551927 ER PT J AU Smith, ME AF Smith, Mary Ellin TI From student to practicing nurse - How institutions, managers, and colleagues can ease the transition. SO AMERICAN JOURNAL OF NURSING LA English DT Article ID GRADUATE NURSES C1 Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. RP Smith, ME (reprint author), Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. EM nesmith@partners.org NR 10 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUL PY 2007 VL 107 IS 7 BP 72A EP 72D PG 4 WC Nursing SC Nursing GA 188AH UT WOS:000247890200027 ER PT J AU Vivaldelli, J AF Vivaldelli, Joan TI Therapeutic reciprocity - 'A union through pain.' SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. RP Vivaldelli, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM joanvivaldelli@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUL PY 2007 VL 107 IS 7 BP 74 EP + PG 2 WC Nursing SC Nursing GA 188AH UT WOS:000247890200032 PM 17589244 ER PT J AU Chafetz, I Kuhnreich, I Sammar, M Tal, Y Gibor, Y Meiri, H Cuckle, H Wolf, M AF Chafetz, Ilana Kuhnreich, Ido Sammar, Marei Tal, Yossi Gibor, Yair Meiri, Hamutal Cuckle, Howard Wolf, Myles TI First-trimester placental protein 13 screening for preeclampsia and intrauterine growth restriction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE intrauterine growth restriction; placental protein 13; preeclampsia ID UTERINE-ARTERY-DOPPLER; HUMAN CHORIONIC-GONADOTROPIN; SERUM PAPP-A; HYPERTENSIVE DISORDERS; PREGNANCY COMPLICATIONS; VITAMIN-C; RISK; PREDICTION; TRIMESTER; WOMEN AB OBJECTIVE: The purpose of this study was to evaluate first-trimester serum placental protein 13 (PP13) as a screening test for preeclampsia and intrauterine growth restriction (IUGR). STUDY DESIGN: We performed a prospective, nested case-control study in the Massachusetts General Hospital Obstetric Maternal Study. PP13 was measured by solid- phase sandwich enzyme-linked immunosorbent assay in serum samples that were collected at the first prenatal visit (9-12 weeks of gestation) from women who subsequently experienced preeclampsia (n = 47), IUGR (n = 42), or preterm delivery (n = 46). Women with uncomplicated term deliveries served as control subjects (n = 290) and were matched to cases by gestational age when serum was collected and for the duration of specimen storage. RESULTS: The median first-trimester PP13 level was 132.5 pg/mL in the control subjects. Median PP13 levels were significantly lower among women who had preeclampsia (27.2 pg/ mL; P < .001), IUGR 86.6 pg/mL; P < .001), and preterm delivery (84.9 pg/mL; P = .007). When PP13 was expressed as multiples of the gestational ages-specific medians among the control subjects, the multiples of the medians were 0.2 for preeclampsia, 0.6 for IUGR, and 0.6 for preterm delivery (P < .001 for each disorder compared with control subjects). Receiver operating characteristic analysis yielded areas under the curve of 0.91, 0.65, and 0.60 for preeclampsia, IUGR, and preterm delivery, respectively. At a 90% specificity rate, the corresponding sensitivities were 79%, 33%, and 28%, respectively. CONCLUSION: The screening of maternal PP13 levels in the first trimester is a promising diagnostic tool for the prediction of preeclampsia with high sensitivity and specificity. C1 Harvard Univ, Massachusetts Gen Hosp, Renal Unit, Dept Med,Med Sch, Boston, MA 02114 USA. Diagnost Technol Ltd, Haifa, Israel. TechnoStat Ltd, Kefar Sava, Israel. Univ Leeds, Sch Med, Dept Reprod Epidemiol, Leeds LS2 9JT, W Yorkshire, England. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Renal Unit, Dept Med,Med Sch, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org NR 38 TC 14 Z9 14 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2007 VL 197 IS 1 AR 35.e2 DI 10.1016/j.ajog.2007.02.025 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 188HH UT WOS:000247910500019 ER PT J AU Papadaki, TG Zacharopoulos, IP Pasquale, LR Christen, WB Netland, PA Foster, CS AF Papadaki, Thekla G. Zacharopoulos, Ioannis P. Pasquale, Louis R. Christen, William B. Netland, Peter A. Foster, C. Stephen TI Long-term results of Ahmed glaucoma valve implantation for uveitic glaucoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ADJUNCTIVE MITOMYCIN-C; FOLLOW-UP; PENETRATING KERATOPLASTY; SECONDARY GLAUCOMA; TRABECULECTOMY; SURGERY; EYES AB PURPOSE: To present long-term outcomes of Ahmed glaucoma valve implantation for uveitic glaucoma. DESIGN: Interventional case series. METHODS: Retrospective chart review of 60 patients (60 eyes) with uveitic glaucoma who underwent Ahmed valve implantation over a four-year period at a tertiary uveitis referral center. Success definition I included patients with an intraocular pressure (IOP) between 5 and 21 mm Hg, reduced by 25% from that before implantation. Success definition 2 (qualified success) excluded those patients in whom serious complications occurred. RESULTS- Mean follow,up time was 30 months (range, six to 87 months; four,year results relate to a cohort of 15 patients). Success rates were 77% and 50% and qualified success rates were 57% and 39% at one and four years, respectively. At four years, 74% of the patients required glaucoma medication to maintain IOP? control. The overall complication rate was 12%/person, years. The rate of visual acuity loss was 4%/person, years; that was most commonly attributed to corneal complications that were more likely to occur in patients with preoperative corneal disease (P = .01, Fisher exact test). CONCLUSIONS: Ahmed glaucoma valve implantation is * safe yet moderately successful procedure for uveitic glaucoma. Long-term success rates are enhanced with the use of glaucoma medications, and corneal complications are the most common of all potential serious complications. C1 Harvard Univ, Sch Med, Massachusetts Eye Res & Surg Inst, Ocular Immunol & Uveitis Fdn, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02115 USA. Univ Memphis, Glaucoma Serv, Memphis, TN 38152 USA. RP Papadaki, TG (reprint author), Univ Crete, Dept Ophthalmol, 40 Anopoleos St, Iraklion 71201, Crete, Greece. EM theklapap@med.uoc.gr NR 25 TC 46 Z9 50 U1 0 U2 2 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 JUL PY 2007 VL 144 IS 1 BP 62 EP 69 DI 10.1016/j.ajo.2007.03.013 PG 8 WC Ophthalmology SC Ophthalmology GA 187SD UT WOS:000247867800010 PM 17493574 ER PT J AU Bourla, DH Sarraf, D Schwartz, SD AF Bourla, Dan H. Sarraf, David Schwartz, Steven D. TI Peripheral retinopathy and Maculopathy in high-dose tamoxifen therapy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To describe the clinical, angiographic, and optical coherence tomography (OCT) features of high-dose tamoxifen retinopathy in three male patients. DESIGN: Observational case series. METHODS: A review of history, clinical examination, and findings on fluorescein angiography (FA) and optical coherence tomography (OCT) was conducted. RESULTS: Three male patients receiving high-dose tamoxifen therapy sought treatment for vision loss and a crystalline maculopathy. Crystalline deposits were noted in the peripheral retina of two patients. All the patients showed macular leakage by FA, but cystoid macular edema (CME) on OCT was detected in two patients. Inner retinal hyperreflective deposits were identified by OCT in all the patients. CONCLUSIONS: High-dose tamoxifen therapy may result in peripheral crystalline retinopathy in addition to perifoveal opacities. Angiographic evidence of macular edema may not unanimously correlate with presence of CME on OCT in these cases. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. King Drew Med Ctr, Los Angeles, CA USA. RP Bourla, DH (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, 200 Stein Pl, Los Angeles, CA 90095 USA. EM bourla@jsei.ucla.edu NR 5 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2007 VL 144 IS 1 BP 126 EP 128 DI 10.1016/j.ajo.2007.03.023 PG 3 WC Ophthalmology SC Ophthalmology GA 187SD UT WOS:000247867800023 PM 17601434 ER PT J AU Collins, JF Dartt, DA Dana, R AF Collins, James F. Dartt, Darlene A. Dana, Reza TI Mist delivery of eye medication to the anterior segment SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To compare the mydriatic efficacies of mist and drop delivery of tropicamide 1.0%. DESIGN: Randomized, masked, active, controlled clinical trial. METHODS: One hundred subjects were randomized to receive small,volume (6 mu l) mist administration of tropicamide 1.0% in one eye and either nothing or a conventional drop (30 mu l) of the same solution in the fellow eye. RESULTS: Comparing misted eyes with untreated eyes in the same subjects, the mean maximal increase in pupil diameter in the misted eyes was 2.02 ram. and was 0.25 mm in the fellow eyes. The difference is statistically significant (P <= .001) Comparing mist,treated eyes with drop treated eyes in the same subjects, the mean maximal increase in pupil diameter in the misted eyes was 1.98 mm and was 2.11 mm in the drop-treated eyes. The difference was not statistically significant (P =.051). CONCLUSIONS: Small-volume mist and conventional drop delivery of tropicamide 1.0% were shown to be similar in mydriatic effectiveness. C1 Ctr Eye Care & Opt, W Islip, NY 11795 USA. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02115 USA. RP Collins, JF (reprint author), Ctr Eye Care & Opt, 360 Montauk Highway, W Islip, NY 11795 USA. EM optimystsystems@gmail.com NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2007 VL 144 IS 1 BP 137 EP 139 DI 10.1016/j.ajo.2007.03.022 PG 3 WC Ophthalmology SC Ophthalmology GA 187SD UT WOS:000247867800028 PM 17601439 ER PT J AU Lee, BW Jurkunas, UV Harissi-Dagher, M Poothullil, AM Tobaigy, FM Azar, DT AF Lee, Brandon W. Jurkunas, Ula V. Harissi-Dagher, Mona Poothullil, Antony M. Tobaigy, Faisal M. Azar, Dimitri T. TI Ectatic disorders associated with a claw-shaped pattern on corneal topography SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DEGENERATION AB PURPOSE: To identify clinical findings associated with claw-shaped patterns on corneal topography. DESIGN: Retrospective, observational case series. METHODS: Forty eyes (26 patients) with classic claw-shaped patterns on corneal topography were identified from 3,993 Orbscan 11 records. They were subclassified into three groups: Group 1 (pellucid marginal degeneration [PMD] or PMD suspect); group 2 (keratoconus or keratoconus suspect); and group 3 (ectasia). The refractive and topographic indices of groups 1 and 2 were compared. RESULTS: There were nine eyes (six patients) in group 1, 27 eyes (18 patients) in group 2, and four eyes (two patients) in group 3. The mean radii of maximal anterior (2.96 mm) and posterior (3.06 mm) elevation in group 1 were significantly greater than those of group 2 (1.89 mm; P =.018 and 1.72 mm; P =.022, respectively). CONCLUSIONS: The claw,shaped pattern on corneal topography is not diagnostic of PMD; it is also seen in keratoconus. C1 Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. RP Azar, DT (reprint author), Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu NR 7 TC 29 Z9 29 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 JUL PY 2007 VL 144 IS 1 BP 154 EP 157 DI 10.1016/j.ajo.2007.02.032 PG 4 WC Ophthalmology SC Ophthalmology GA 187SD UT WOS:000247867800037 PM 17601448 ER PT J AU Farris, W Schutz, SG Cirrito, JR Shankar, GM Sun, XY George, A Leissring, MA Walsh, DM Qiao, W Holtzman, DM Selkoe, DJ AF Farris, Wesley Schutz, Sonja G. Cirrito, John R. Shankar, Ganesh M. Sun, Xiaoyan George, Ana Leissring, Malcolm A. Walsh, Dominic M. Qiao, Wei Holtzman, David M. Selkoe, Dennis J. TI Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INSULIN-DEGRADING ENZYME; ENDOTHELIN-CONVERTING ENZYME; ONSET ALZHEIMERS-DISEASE; PROTEIN A-BETA; LEVELS IN-VIVO; INTERSTITIAL FLUID; TRANSGENIC MICE; EXTRACELLULAR LEVELS; MOUSE-BRAIN; PEPTIDE AB Cerebral deposition of the amyloid 6 protein (A beta), an invariant feature of Alzheimer's disease, reflects an imbalance between the rates of A beta production and clearance. The causes of A beta elevation in the common late-onset form of Alzheimer's disease (LOAD) are largely unknown. There is evidence that the A beta-degrading protease neprilysin (NEP) is down-regulated in normal aging and LOAD. We asked whether a decrease in endogenous NEP levels can prolong the half-life of A,6 in vivo and promote development of the classic amyloid neuropathology of Alzheimer's disease. We examined the brains and plasma of young and old mice expressing relatively low levels of human amyloid precursor protein and having one or both NEP genes silenced. NEP loss of function 1) elevated whole-brain and plasma levels of human AB(40) and A beta 42, 2) prolonged the half-life of soluble A beta in brain interstitial fluid of awake animals, 3) raised the concentration of A beta dimers, 4) markedly increased hippocampal amyloid plaque burden, and 5) led to the development of amyloid angiopathy. A similar to 50% reduction in NEP levels, similar to that reported in some LOAD brains, was sufficient to increase amyloid neuropathology. These findings demonstrate an important role for proteolysis in determining the levels of A,6 and A beta-associated neuropathology in vivo and support the hypothesis that primary defects in A beta clearance can cause or contribute to LOAD pathogenesis. C1 Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA. Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Scripps Res Inst, Jupiter, FL USA. Scripps Florida, Jupiter, FL USA. Univ Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Dublin 2, Ireland. RP Farris, W (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh Inst Neurodegenerat Dis, 3501 5th Ave,BST3 7019, Pittsburgh, PA 15260 USA. EM farrisw@upmc.edu; dselkoe@rics.bwh.harvard.edu OI Qiu, Wendy/0000-0002-2082-2410 FU NIA NIH HHS [AG13956, K23 AG022476, AG12749, R01 AG012749, R01 AG013956, AG022476, R37 AG013956]; NIDA NIH HHS [DA07261, T32 DA007261]; NINDS NIH HHS [K08 NS046324, NS046324] NR 53 TC 79 Z9 81 U1 1 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2007 VL 171 IS 1 BP 241 EP 251 DI 10.2353/ajpath.2007070105 PG 11 WC Pathology SC Pathology GA 185LO UT WOS:000247712700024 PM 17591969 ER PT J AU Da Silva, N Shum, WWC El-Annan, J Paunescu, TG Mckee, M Smith, PJS Brown, D Breton, S AF Da Silva, Nicolas Shum, Winnie W. C. El-Annan, Jaafar Paunescu, Teodor G. McKee, Mary Smith, Peter J. S. Brown, Dennis Breton, Sylvie TI Relocalization of the V-ATPase B2 subunit to the apical membrane of epididymal clear cells of mice deficient in the B1 subunit SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE male reproductive tract; male fertility; luminal acidification; proton pump; vacuolar H(+)ATPase ID VACUOLAR H+-ATPASE; MALE REPRODUCTIVE-TRACT; RENAL TUBULAR-ACIDOSIS; PROTON PUMP ATPASE; RAT EPIDIDYMIS; EPITHELIAL-CELLS; INTERCALATED CELLS; OSTEOCLAST DIFFERENTIATION; CARBONIC-ANHYDRASE; PLASMA-MEMBRANE AB An acidic luminal pH in the epididymis contributes to maintaining sperm quiescent during their maturation and storage. The vacuolar H+ ATPase (V-ATPase), located in narrow and clear cells, is a major contributor to luminal acidification. Mutations in one of the V-ATPase subunits, ATP6v1B1 (B1), cause distal renal tubular acidosis in humans but surprisingly, B1(-/-) mice do not develop metabolic acidosis and are fertile. While B1 is located in the apical membrane of narrow and clear cells, the B2 subunit localizes to subapical vesicles in wild-type mouse, rat and human epididymis. However, a marked increase (84%) in the mean pixel intensity of B2 staining was observed in the apical pole of clear cells by conventional immunofluorescence, and relocalization into their apical membrane was detected by confocal microscopy in B1(-/-) mice compared with B1(-/-). Immunogold electron microscopy showed abundant B2 in the apical microvilli of clear cells in B1(-/-) mice. B2 mRNA expression, determined by real time RT-PCR using laser-microdissected epithelial cells, was identical in both groups. Semiquantitative Western blots from whole epididymis and cauda epididymidis showed no variation of B2 expression. Finally, the luminal pH of the cauda epididymidis was the same in B1(-/-) mice as in B1(+/+) (pH 6.7). These data indicate that whereas overall expression of B2 is not affected in B1(-/-) mice, significant redistribution of B2-containing complexes occurs from intracellular compartments into the apical membrane of clear cells in B1(-/-) mice. This relocation compensates for the absence of functional B1 and maintains the luminal pH in an acidic range that is compatible with fertility. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Nephrol Div, Boston, MA 02114 USA. Biol Marine Lab, Biocurrents Res Ctr, Woods Hole, MA USA. RP Da Silva, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Nephrol Div, 185 Cambridge St,CPZN 8150, Boston, MA 02114 USA. EM ndasilva@partners.org FU NICHD NIH HHS [HD-40793]; NIDDK NIH HHS [DK-43351, DK-57521, DK-73266, DK-38452] NR 63 TC 30 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2007 VL 293 IS 1 BP C199 EP C210 DI 10.1152/ajpcell.00596.2006 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 189DF UT WOS:000247968900022 PM 17392376 ER PT J AU Lo, J Bernstein, LE Canavan, B Torriani, M Jackson, MB Ahima, RS Grinspoon, SK AF Lo, Janet Bernstein, L. Elizabeth Canavan, Bridget Torriani, Martin Jackson, Malaka B. Ahima, Rexford S. Grinspoon, Steven K. TI Effects of TNF-alpha neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE tumor necrosis factor-alpha; adiponectin; resistin; muscle adiposity; metabolic syndrome ID TUMOR-NECROSIS-FACTOR; COMPLEMENT-RELATED PROTEIN; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; FACTOR RECEPTOR; RHEUMATOID-ARTHRITIS; COMPUTED-TOMOGRAPHY; LIPOPROTEIN-LIPASE; 3T3-L1 ADIPOCYTES; HUMAN ADIPONECTIN AB In a prior study, we have shown that tumor necrosis factor (TNF)-alpha neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF-alpha neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (-0.03 +/- 0.03 vs. 0.06 +/- 0.03, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (-0.6 +/- 0.7 vs. 1.2 +/- 0.7 ng/ml, P = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [-0.61 +/- 0.64 Hounsfield units (HU) vs. 1.54 +/- 0.77 HU in placebo, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate that neutralization of TNF-alpha in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF-alpha neutralization in obesity. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Diabet Endocrinol & Metab, Philadelphia, PA 19104 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [K30 RR-022292-07, K30 RR022292, M01 RR-01066-25S1, M01 RR001066]; NICHD NIH HHS [T32 HD052961, T32 HD-052961-01A]; NIDDK NIH HHS [P01 DK-49210, P01 DK049210, P30 DK040561, P30 DK040561-12] NR 59 TC 56 Z9 57 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2007 VL 293 IS 1 BP E102 EP E109 DI 10.1152/ajpendo.00089.2007 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 190OJ UT WOS:000248068200014 PM 17374698 ER PT J AU Zalutskaya, AA Arai, M Bounoutas, GS Abou-Samra, AB AF Zalutskaya, Alena A. Arai, Maya Bounoutas, George S. Abou-Samra, Abdul B. TI Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE corticosterone; stress; mice ID CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RNA EXPRESSION; ANXIETY-LIKE BEHAVIOR; TYPE-2 CRF RECEPTORS; MULTIPLE G-PROTEINS; HORMONE-RECEPTORS; CHRONIC STRESS; RAT-BRAIN; PITUITARY; IDENTIFICATION AB Urocortin 1 (UCN1) is a corticotropin-releasing factor (CRF)-like peptide whose role in stress is not well characterized. To study the physiological role of UCN1 in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress, we generated UCN1-knockout (KO) mice and examined their adaptation to repeated restraint and to cold environment. Wild-type (WT) and UCN1-KO animals were restrained hourly for 15 min from 9 AM to 2 PM, and blood samples were obtained for corticosterone measurement. WT animals adapted to repeated restraint with a decreased corticosterone response; the restraint-stimulated corticosterone levels fell from 215 +/- 31 ng/mI in naive animals to 142 +/- 50 ng/mI in mice subjected to repeated restraint (P < 0.01) and from 552 +/- 98 to 314 +/- 58 ng/mI (P < 0.001) in males and females, respectively. Male UCN1-KO mice did not show any adaptation to repeated restraint; instead, restraint-stimulated corticosterone levels were increased from 274 +/- 80 ng/ml in nalve animals to 480 +/- 75 ng/mI in mice subjected to repeated restraint (P < 0.001). Female UCN1-KO mice showed only a partial adaptation to repeated restraint, with a decrease in the restraint-stimulated corticosterone response from 631 +/- 102 ng/mI in nalve animals to 467 +/- 78 ng/mI in mice subjected to repeated restraint (P < 0.01). In addition, UCN1-KO mice showed no corticosterone response to 2-h cold environment. These data demonstrate an important role for UCN1 in the HPA axis adaptation to repeated restraint and in the corticosterone response to a cold environment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Wayne State Univ, Sch Med, Detroit, MI 48201 USA. RP Zalutskaya, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,55 Fruit St, Boston, MA 02114 USA. EM azalutskaya@partners.org OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [5R01-DK-063211] NR 34 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2007 VL 293 IS 1 BP E259 EP E263 DI 10.1152/ajpendo.00616.2006 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 190OJ UT WOS:000248068200033 PM 17456638 ER PT J AU Kohler, H Sakaguchi, T Hurley, BP Kase, BJ Reinecker, HC McCormick, BA AF Koehler, Henrik Sakaguchi, Takanori Hurley, Bryan P. Kase, Benjamin J. Reinecker, Hans-Christian McCormick, Beth A. TI Salmonella enterica serovar Typhimurium regulates intercellular junction proteins and facilitates transepithelial neutrophil and bacterial passage SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE epithelial barrier; mucosal immunology; tight junctions; host defense ID TIGHT JUNCTION; INTESTINAL EPITHELIA; ESCHERICHIA-COLI; BARRIER FUNCTION; CELLS; OCCLUDIN; SECRETION; MIGRATION; IDENTIFICATION; MONOLAYERS AB The establishment of tight junctions (TJ) between columnar epithelial cells defines the functional barrier, which enteroinvasive pathogens have to overcome. Salmonella enterica serovar Typhimurium (S. typhimurium) directly invades intestinal epithelial cells but it is not well understood how the pathogen is able to overcome the intestinal barrier and gains access to the circulation. Therefore, we sought to determine whether infection with S. typhimurium could regulate the molecular composition of the TJ and, if so, whether these modifications would influence bacterial translocation and polymorphonuclear leukocyte (PMN) movement across model intestinal epithelium. We found that infection of a model intestinal epithelium with S. typhimurium over 2 h resulted in an similar to 80% loss of transepithelial electrical resistance. Western blot analysis of epithelial cell lysates demonstrated that S. typhimurium regulated the distribution of the TJ complex proteins claudin-1, zonula occludens (ZO)-2, and E-cadherin in Triton X-100-soluble and insoluble fractions. In addition, S. typhimurium was specifically able to dephosphorylate occludin and degrade ZO-1. This TJ alteration in the epithelial monolayer resulted in 10-fold increase in bacterial translocation and a 75% increase in N-formylmethionin-leucylphenyalanineinduced PMN transepithelial migration. Our data demonstrate that infection with S. typhimurium is associated with the rapid targeting of the tight junctional complex and loss of barrier function. This results in enhanced bacterial translocation and initiation of PMN migration across the intestinal barrier. Therefore, the ability to regulate the molecular composition of TJs facilitates the pathogenicity of S. typhimurium by aiding its uptake and distribution within the host. C1 Massachusetts Gen Hosp, Mucosal Immunol Labs, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Labs, Combined Program Pediat Gastroenterol & Nutr, CNY 114 16th St,114-3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 33506, DK 56754] NR 50 TC 57 Z9 57 U1 2 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 2007 VL 293 IS 1 BP G178 EP G187 DI 10.1152/ajpgi.00535.2006 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 190QX UT WOS:000248075100020 PM 17615177 ER PT J AU Buys, ES Raher, MJ Blake, SL Neilan, TG Graveline, AR Passeri, JJ Llano, M Perez-Sanz, TM Ichinose, F Janssens, S Zapol, WM Picard, MH Bloch, KD Scherrer-Crosbie, M AF Buys, Emmanuel S. Raher, Michael J. Blake, Sarah L. Neilan, Tomas G. Graveline, Amanda R. Passeri, Jonathan J. Llano, Miguel Perez-Sanz, Teresa M. Ichinose, Fumito Janssens, Stefan Zapol, Warren M. Picard, Michael H. Bloch, Kenneth D. Scherrer-Crosbie, Marielle TI Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE echocardiography; heart failure; hypertrophy; mice ID NITRIC-OXIDE SYNTHASE; CONGESTIVE-HEART-FAILURE; ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; HYPERTROPHY; DYSFUNCTION; OVEREXPRESSION; MICE; STRESS; LOAD AB Although nitric oxide synthase (NOS) 3 is implicated as an important modulator of left ventricular (LV) remodeling, its role in the cardiac response to chronic pressure overload is controversial. We examined whether selective restoration of NOS3 to the hearts of NOS3-deficient mice would modulate the LV remodeling response to transverse aortic constriction (TAC). LV structure and function were compared at baseline and after TAC in NOS3-deficient (NOS3(-/-)) mice and NOS3(-/-) mice carrying a transgene directing NOS3 expression specifically in cardiomyocytes (NOS3(-/-TG) mice). At baseline, echocardiographic assessment of LV dimensions and function, invasive hemodynamic measurements, LV mass, and myocyte width did not differ between the two genotypes. Four weeks after TAC, echocardiographic and hemodynamic indexes of LV systolic function indicated that contractile performance was better preserved in NOS3(-/-TG) mice than in NOS3(-/-) mice. Echocardiographic LV wall thickness and cardiomyocyte width were greater in NOS3(-/-) mice than in NOS3(-/-TG) mice. TAC-induced cardiac fibrosis did not differ between these genotypes. TAC increased cardiac superoxide generation in NOS3(-/-TG) but not NOS3(-/-) mice. The ratio of NOS3 dimers to monomers did not differ before and after TAC in NOS3(-/-TG) mice. Restoration of NOS3 to the heart of NOS3-deficient mice attenuates LV hypertrophy and dysfunction after TAC, suggesting that NOS3 protects against the adverse LV remodeling induced by prolonged pressure overload. C1 Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Sch Med, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div,Cardiac Ultrasound Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. Univ Louvain, Ctr Transgene Technol & Gene Therapy, Div Cardiol, Louvain, Belgium. RP Scherrer-Crosbie, M (reprint author), Cardiac Ultrasound Lab, 55 Fruit St,Blake 254, Boston, MA 02115 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL 71987, HL 42397, HL 70896]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 27 TC 50 Z9 50 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2007 VL 293 IS 1 BP H620 EP H627 DI 10.1152/ajpheart.01236.2006 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 189DE UT WOS:000247968800075 PM 17416602 ER PT J AU Thibault, H Gomez, L Donal, E Pontier, G Scherrer-Crosbie, M Ovize, M Derumeaux, G AF Thibault, Helene Gomez, Ludovic Donal, Erwan Pontier, Gerard Scherrer-Crosbie, Marielle Ovize, Michel Derumeaux, Genevieve TI Acute myocardial infarction in mice: assessment of transmurality by strain rate imaging SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE echocardiography; murine model ID EMISSION COMPUTED-TOMOGRAPHY; LEFT-VENTRICULAR FUNCTION; MURINE MODEL; DOPPLER-ECHOCARDIOGRAPHY; ISCHEMIA-REPERFUSION; SIZE; VIABILITY; INJURY; EXTENT; MOUSE AB In vivo evaluation of the transmural extension of myocardial infarction (TEI) is crucial to prediction of viability and prognosis. With the rise of transgenic technology, murine myocardial infarction (MI) models are increasingly used. Our study aimed to evaluate systolic strain rate (SR), a new parameter of regional function, to quantify TEI in a murine model of acute MI induced by various durations of ischemia followed by 24 h of reperfusion. Global and regional left ventricular (LV) function were assessed by echocardiography (13 MHz, Vivid 7, GE) in 4 groups of wild-type mice (C57BL/6, 2 mo old): a sham-treated group (n = 10) and three MI groups [30 (n = 11), 60 (n = 10), and 90 (n = 9) min of left coronary artery occlusion]. Conventional LV dimensions, anterior wall (AW) thickening, and peak systolic SR were measured before and 24 h after reperfusion. Area at risk (AR) was measured by blue dye and infarct size (area of necrosis, AN) and TEI by triphenyltetrazolium chloride staining. AN increased with ischemia duration (25 +/- 2%, 56 +/- 5%, 71 +/- 6% of AR for 30, 60, and 90 min, respectively; P < 0.05). LV end-diastolic volume significantly increased with ischemia duration (30 +/- 5, 34 +/- 5, 43 +/- 5 mu l; P < 0.05), whereas LV ejection fraction decreased (63 +/- 5%, 58 +/- 6%, 46 +/- 5%; P < 0.05). AW thickening decrease was not influenced by ischemia duration. Conversely, systolic SR decreased with ischemia duration (13 +/- 5, 4 +/- 3, +/- 2 +/- 6 s(-1); P < 0.05) and was significantly correlated with TEI (r = 0.89, P < 0.01). Receiver operating characteristic (ROC) curves identified systolic SR as the most accurate parameter to predict TEI. In conclusion, in a murine model of MI, SR imaging is superior to conventional echocardiography to predict TEI early after MI. C1 Univ Lyon 1, INSERM, E 0226, F-69365 Lyon, France. Hop Louis Pradel, Hospices Civils Lyon, Lyon, France. Hop Pontchaillou, Rennes, France. Hop Charles Nicolle, Rouen, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Derumeaux, G (reprint author), Fac Med Lyon, INSERM, E 0226, 8,Ave Rockefeller, F-69373 Lyon 8, France. EM genevieve.derumeaux@chu-lyon.fr NR 46 TC 31 Z9 35 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2007 VL 293 IS 1 BP H496 EP H502 DI 10.1152/ajpheart.00087.2007 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 189DE UT WOS:000247968800060 PM 17384134 ER PT J AU Watson, PA Reusch, JEB McCune, SA Leinwand, LA Luckey, SW Konhilas, JP Brown, DA Chicco, AJ Sparagna, GC Long, CS Moore, RL AF Watson, Peter A. Reusch, Jane E. B. McCune, Sylvia A. Leinwand, Leslie A. Luckey, Stephen W. Konhilas, John P. Brown, David A. Chicco, Adam J. Sparagna, Genevieve C. Long, Carlin S. Moore, Russell L. TI Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE exercise; mitochondria; apoptosis; cyclic-nucleotide regulatory element binding protein ID ELEMENT-BINDING PROTEIN; MUSCLE CELL-PROLIFERATION; HEART-FAILURE; DILATED CARDIOMYOPATHY; CYTOCHROME-C; MITOCHONDRIAL BIOGENESIS; TRANSCRIPTION FACTOR; OXIDATIVE CAPACITY; BRAIN MITOCHONDRIA; MYOCYTE APOPTOSIS AB Potential regulation of two factors linked to physiological outcomes with left ventricular (LV) hypertrophy, resistance to apoptosis, and matching of metabolic capacity, by the transcription factor cyclic-nucleotide regulatory element binding protein (CREB), was examined in the two models of physiological LV hypertrophy: involuntary treadmill running of female Sprague-Dawley rats and voluntary exercise wheel running in female C57Bl/6 mice. Comparative studies were performed in the models of pathological LV hypertrophy and failure: the spontaneously hypertension heart failure (SHHF) rat and the hypertrophic cardiomyopathy (HCM) transgenic mouse, a model of familial idiopathic cardiomyopathy. Activating CREB serine-133 phosphorylation was decreased early in remodeling in response to both physiological (decreased 50-80%) and pathological (decreased 60-80%) hypertrophic stimuli. Restoration of LV CREB phosphorylation occurred concurrent with completion of physiological hypertrophy (94% of sedentary control), but remained decreased (by 90%) during pathological hypertrophy. In all models of hypertrophy, CREB phosphorylation/ activation demonstrated strong positive correlations with 1) expression of the anti-apoptotic protein bcl-2 ( a CREB-dependent gene) and subsequent reductions in the activation of caspase 9 and caspase 3; 2) expression of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1; a major regulator of mitochondrial content and respiratory capacity), and 3) LV mitochondrial respiratory rates and mitochondrial protein content. Exercise-induced increases in LV mitochondrial respiratory capacity were commensurate with increases observed in LV mass, as previously reported in the literature. Exercise training of SHHF rats and HCM mice in LV failure improved cardiac phenotype, increased CREB activation (31 and 118%, respectively), increased bcl-2 content, improved apoptotic status, and enhanced PGC-1 content and mitochondrial gene expression. Adenovirus-mediated expression of constitutively active CREB in neonatal rat cardiac recapitulated exercise-induced upregulation of PGC-1 content and mitochondrial oxidative gene expression. These data support a model wherein CREB contributes to physiological hypertrophy by enhancing expression of genes important for efficient oxidative capacity and resistance to apoptosis. C1 Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Colorado, Boulder, CO 80309 USA. Myogen Inc, Boulder, CO USA. RP Watson, PA (reprint author), Denver VA Med Ctr, 111H,1055 Clermont St, Denver, CO 80220 USA. EM pete.watson@uchsc.edu RI Moore, Russell/D-1040-2013; OI Moore, Russell/0000-0002-6727-8985; LEINWAND, LESLIE/0000-0003-1470-4810 FU NHLBI NIH HHS [HL 40306-15]; NIDDK NIH HHS [R01 DK 06741]; PHS HHS [DERC 57576, P01 56481] NR 60 TC 46 Z9 46 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2007 VL 293 IS 1 BP H246 EP H259 DI 10.1152/ajpheart.00734.2006 PG 14 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 189DE UT WOS:000247968800031 PM 17337597 ER PT J AU Frank, JA Briot, R Lee, JW Ishizaka, A Uchida, T Matthay, MA AF Frank, James A. Briot, Raphael Lee, Jae Woo Ishizaka, Akitoshi Uchida, Tokujiro Matthay, Michael A. TI Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE alveolar epithelial fluid transport; acute lung injury; acute respiratory distress syndrome; lung transplantation; biological markers; pulmonary edema; primary graft failure; air space fluid clearance ID RESPIRATORY-DISTRESS-SYNDROME; FLUID CLEARANCE; PULMONARY-EDEMA; LIQUID CLEARANCE; PROTEIN CLEARANCE; UP-REGULATION; RAT LUNGS; IN-SITU; TRANSPLANTATION; INJURY AB To study air space fluid clearance ( AFC) under conditions that resemble the clinical setting of pulmonary edema in patients, we developed a new perfused human lung preparation. We measured AFC in 20 human lungs rejected for transplantation and determined the contribution of AFC to lung fluid balance. AFC was then compared with air space and perfusate levels of a biological marker of epithelial injury. The majority of human lungs rejected for transplant had intact basal ( 75%) and beta(2)-adrenergic agonist-stimulated ( 70%) AFC. For lungs with both basal and stimulated AFC, the basal AFC rate was 19 +/- 10%/ h, and the beta(2)-adrenergic- stimulated AFC rate was 43 +/- 13%/ h. Higher rates of AFC were associated with less lung weight gain ( Pearson coefficient -0.90, P < 0.0001). Air space and perfusate levels of the type I pneumocyte marker receptor for advanced glycation end products ( RAGE) were threefold and sixfold higher, respectively, in lungs without basal AFC compared with lungs with AFC ( P < 0.05). These data show that preserved AFC is a critical determinant of favorable lung fluid balance in the perfused human lung, raising the possibility that beta(2)-agonist therapy to increase edema fluid clearance may be of value for patients with acute lung injury and pulmonary edema. Also, although additional studies are needed, a biological marker of alveolar epithelial injury may be useful clinically in predicting preserved AFC. C1 Univ Calif San Francisco, Cardiovasc Res Inst, No Calif Inst Res & Educ, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94121 USA. No Calif Inst Res & Educ, San Francisco Vet Adm Med Ctr, San Francisco, CA USA. Keio Univ, Dept Med, Tokyo, Japan. Tokyo Med & Dent Univ, Dept Anesthesiol, Tokyo, Japan. RP Frank, JA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, No Calif Inst Res & Educ, San Francisco Vet Affairs Med Ctr, 4150 Clement St,Mail Stop 111D, San Francisco, CA 94121 USA. EM james.frank@ucsf.edu RI BRIOT, Raphael/M-6732-2014 FU NHLBI NIH HHS [R01 HL051856, HL-51856, HL-69900, K08 HL069900, R01 HL088440, R01 HL088440-01A1, R37 HL051856, R37 HL051856-14, R56 HL088440] NR 40 TC 59 Z9 60 U1 0 U2 1 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 JUL PY 2007 VL 293 IS 1 BP L52 EP L59 DI 10.1152/ajplung.00256.2006 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 188FT UT WOS:000247905500008 PM 17351061 ER PT J AU Nakanishi, H Sugiura, T Streisand, JB Lonning, SM Roberts, JD AF Nakanishi, Hidehiko Sugiura, Takahiro Streisand, James B. Lonning, Scott M. Roberts, Jesse D., Jr. TI TGF-beta-neutralizing antibodies improve pulmonary alveologenesis and vasculogenesis in the injured newborn lung SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE bronchopulmonary dysplasia; transforming growth factor-beta ID GROWTH-FACTOR-BETA; BRONCHOPULMONARY-DYSPLASIA; TRANSFORMING GROWTH-FACTOR-BETA-1; VASCULAR DEVELOPMENT; MOUSE LUNG; RETINOIC ACID; HYPEROXIA; MICE; RAT; EXPRESSION AB Pulmonary injury is associated with the disruption of alveologenesis in the developing lung and causes bronchopulmonary dysplasia ( BPD) in prematurely born infants. Transforming growth factor ( TGF)-beta is an important regulator of cellular differentiation and early lung development, and its levels are increased in newborn lung injury. Although overexpression of TGF-beta in the lungs of newborn animals causes pathological features that are consistent with BPD, the role of endogenous TGF-beta in the inhibition of the terminal stage of lung development is incompletely understood. In this investigation, the hypothesis that O-2-induced injury of the maturing lung is associated with TGF-beta- mediated disruption of alveologenesis and microvascular development was tested using a murine model of BPD. Here we report that treatment of developing mouse lungs with TGF-beta-neutralizing antibodies attenuates the increase in pulmonary cell phospho-Smad2 nuclear localization, which is indicative of augmented TGF-beta signaling, associated with pulmonary injury induced by chronic inhalation of 85% oxygen. Importantly, the neutralization of the abnormal TGF-beta activity improves quantitative morphometric indicators of alveologenesis, extracellular matrix assembly, and microvascular development in the injured developing lung. Furthermore, exposure to anti- TGF-beta antibodies is associated with improved somatic growth in hyperoxic mouse pups and not with an increase in pulmonary inflammation. These studies indicate that excessive pulmonary TGF-beta signaling in the injured newborn lung has an important role in the disruption of the terminal stage of lung development. In addition, they suggest that anti- TGF-beta antibodies may be an effective therapy for preventing some important developmental diseases of the newborn lung. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Newborn Med, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Genzyme Corp, Cambridge, MA USA. RP Roberts, JD (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM roberts@cvrc.mgh.harvard.edu NR 70 TC 63 Z9 66 U1 0 U2 2 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 JUL PY 2007 VL 293 IS 1 BP L151 EP L161 DI 10.1152/ajplung.00389.2006 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 188FT UT WOS:000247905500019 PM 17400601 ER PT J AU Velez, JCQ Bland, AM Arthur, JM Raymond, JR Janech, MG AF Velez, Juan Carlos Q. Bland, Alison M. Arthur, John M. Raymond, John R. Janech, Michael G. TI Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY NOV 14-19, 2006 CL San Diego, CA SP Amer Soc Nephrol DE angiotensin II; angiotensin-(1-7); neprilysin; ACE2; aminopeptidase A ID HUMAN MESANGIAL CELLS; CONVERTING-ENZYME; HIGH GLUCOSE; PROXIMAL TUBULES; AMINOPEPTIDASE-A; MESSENGER-RNA; EXPRESSION; KIDNEY; RATS; GLOMERULOSCLEROSIS AB Intraglomerular ANG II has been linked to glomerular injury. However, little is known about the contribution of podocytes (POD) to intraglomerular ANG II homeostasis. The aim of the present study was to examine the processing of angiotensin substrates by cultured POD. Our approach was to use matrix-assisted laser desorption/ ionization time-of-flight (MALDITOF) mass spectrometry for peptide determination from conditioned cell media and customized AQUA peptides for quantification. Immortalized mouse POD were incubated with 1-2 mu M ANG I, ANG II, or the renin substrate ANG-(1-14) for different time intervals and coincubated in parallel with various inhibitors. Human mesangial cells (MES) were used as controls. POD incubated with 1 mu M ANG I primarily formed ANG-(1-9) and ANG-(1-7). In contrast, MES incubated with ANG I primarily generated ANG II. In POD, ANG-(1-7) was the predominant product, and its formation was inhibited by a neprilysin inhibitor. Modest angiotensin-converting enzyme (ACE) activity was also detected in POD, although only after cells were incubated with 2 mu M ANG I. In addition, we observed that POD degraded ANG II into ANG III and ANG-(1-7). An aminopeptidase A inhibitor inhibited ANG III formation, and an ACE2 inhibitor led to ANG II accumulation. Furthermore, we found that POD converted ANG-(1-14) to ANG I and ANG-(1-7). This conversion was inhibited by a renin inhibitor. These findings demonstrate that POD express a functional intrinsic renin-angiotensin system characterized by neprilysin, aminopeptidase A, ACE2, and renin activities, which predominantly lead to ANG-(1- 7) and ANG-(1- 9) formation, as well as ANG II degradation. These findings may reflect a specific role of POD in maintenance of intraglomerular renin-angiotensin system balance. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Res, Charleston, SC USA. RP Velez, JCQ (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,Clin Sci Bldg,Rm 829, Charleston, SC 29425 USA. EM velezj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811 FU NHLBI NIH HHS [N01-HV-28181] NR 55 TC 57 Z9 64 U1 0 U2 3 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 JUL PY 2007 VL 293 IS 1 BP F398 EP F407 DI 10.1152/ajprenal.00050.2007 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 187LZ UT WOS:000247850500050 PM 17429035 ER PT J AU Limbos, MA Chan, LS Warf, C Schneir, A Iverson, E Shekelle, P Kipke, MD AF Limbos, Mary Ann Chan, Linda S. Warf, Curren Schneir, Arlene Iverson, Ellen Shekelle, Paul Kipke, Michele D. TI Effectiveness of interventions to prevent youth violence - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID SERIOUS JUVENILE-OFFENDERS; AMERICAN ADOLESCENT MALES; SAFE DATES PROGRAM; DARE PLUS PROJECT; MIDDLE SCHOOL; FOLLOW-UP; CONFLICT-RESOLUTION; OUTCOME EVALUATION; REDUCING VIOLENCE; SUBSTANCE-ABUSE AB Objectives: To identify interventions effective in preventing youth violent behavior and commonalities of effective and ineffective interventions. Methods: A systematic review of the literature on the effectiveness of youth violence interventions was conducted. Interventions were categorized according to the level of the intervention: primary (implemented universally to prevent the onset of violence), secondary (implemented selectively with youth at increased risk for violence), and tertiary (focused on youth who had already engaged in violent behavior). An intervention was considered effective if one or more violence outcome indicators was reported as significantly different at the p < 0.05 level, and ineffective if none of the violence outcome indicators was significantly different at the p < 0.05 level. Data collection and analysis were conducted in 2003 and updated in 2006. Results: Forty-one studies were included in the review. Overall, 49% of interventions were effective. Tertiary-level interventions were more likely to report effectiveness than primary- or secondary-level interventions. Effective interventions evaluated by randomized controlled trials included Responding in Peaceful and Positive Ways, Aban Aya Youth Project, Moving to Opportunity, Early Community-Based Intervention Program, Childhaven's Therapeutic Child-Care Program, Turning Point: Rethinking Violence, and a multisystemic therapy program. Differences among programs and within subpopulations could not be assessed because of inadequate data. Conclusions: Increasing effectiveness was reported as the level of intervention increased from primary to tertiary. Approaches to evaluate prevention interventions need to be clarified and standardized. C1 RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Univ So Calif, Dept Pediat, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Med Ctr, Div Gen Pediat, Los Angeles, CA USA. Univ So Calif, Med Ctr, Div Res Children Youth & Families, Los Angeles, CA USA. Univ So Calif, Med Ctr, Childrens Hosp Los Angeles, Div Biostat & Outcomes Assessment, Los Angeles, CA USA. Greater Los Angeles Vet Affair Healthcare Syst, Hlth Serv Res & Dev Serv, Los Angeles, CA USA. RP Limbos, MA (reprint author), Childrens Hosp Los Angeles, 4650 Sunset Blvd,Mailstop 76, Los Angeles, CA 90027 USA. EM mlimbos@chla.usc.edu NR 59 TC 40 Z9 40 U1 2 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2007 VL 33 IS 1 BP 65 EP 74 DI 10.1016/j.amepre.2007.02.045 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 184WF UT WOS:000247672600011 PM 17572314 ER PT J AU Cunningham-Sabo, L Carpenter, WR Peterson, JC Anderson, LA Helfrich, CD Davis, SM AF Cunningham-Sabo, Leslie Carpenter, William R. Peterson, Jeffery C. Anderson, Lynda A. Helfrich, Christian D. Davis, Sally M. TI Utilization of prevention research - Searching for evidence SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID BRIEF ALCOHOL INTERVENTION; PRIMARY-HEALTH-CARE; CONTINUOUS QUALITY IMPROVEMENT; CLINICAL-PRACTICE GUIDELINES; KONG CHINESE WOMEN; HIV PREVENTION; GENERAL-PRACTITIONERS; DECISION-MAKING; FAMILY-PRACTICE; SERVICE ORGANIZATIONS AB Objective: Understanding the process of translating prevention research into practice calls for systematic efforts to assess the state of the published literature on the utilization of prevention research in public health programs and policy. This review describes the search strategy, methods, results, and challenges in identifying and reviewing literature relevant to this objective. Methods: Systematic searches of topics related to prevention research in literature published in 1995-2002 revealed 86 empiric articles in 12 public health areas. Results: A lack of uniform terminology, variation in publication sources, and limited descriptions of the stages of research utilization (e.g., adoption and implementation) in the published literature posed major challenges to identifying articles that met study criteria. Most accepted articles assessed the adoption or implementation of prevention research; four examined long-term sustainability. There was approximately equal distribution of reported research set in either health services or public health settings. Few of the articles contained search terms reflecting all four concept areas (prevention, public health, research, and use) targeted by the literature search. Conclusions: Refining terms used in prevention research and research utilization could address lack of shared and unique definitions. Expanded reporting of research utilization stages in reports of prevention research could lead to improved literature searches and contribute to more successful adoption, implementation, and further use of prevention research products. C1 Colorado State Univ, Dept Food Sci & Human Nutr, Ft Collins, CO 80523 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Washington State Univ, Edward R Murrow Sch Commun, Pullman, WA 99164 USA. Ctr Dis Control & Prevent, Div Adult & Commun Hlth, Hlth Aging Program, Atlanta, GA USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ New Mexico, Sch Med, Dept Pediat, Prevent Res Ctr, Albuquerque, NM 87131 USA. RP Cunningham-Sabo, L (reprint author), Colorado State Univ, Dept Food Sci & Human Nutr, Ft Collins, CO 80523 USA. EM Icsabo@cahs.colostate.edu RI Carpenter, William/E-5125-2013; Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768 FU PHS HHS [U48/CCU610818-08] NR 110 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2007 VL 33 IS 1 SU 1 BP S9 EP S20 DI 10.1016/j.amepre.2007.03.010 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 187YD UT WOS:000247884300003 PM 17584594 ER PT J AU Davis, SM Peterson, JC Helfrich, CD Cunningham-Sabo, L AF Davis, Sally M. Peterson, Jeffery C. Helfrich, Christian D. Cunningham-Sabo, Leslie TI Introduction and conceptual model for utilization of prevention research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID HEALTH-PROMOTION; INNOVATIONS; DIFFUSION; BARRIERS; DISEASE; CARE C1 Univ New Mexico Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Pediat, Prevent Res Ctr, Albuquerque, NM 87131 USA. Washington State Univ, Edward R Murrow Sch Commun, Pullman, WA 99164 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res Dev, Seattle, WA USA. Colorado State Univ, Dept Food Sci & Human Nutr, Ft Collins, CO 80523 USA. RP Davis, SM (reprint author), Univ New Mexico Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, MSC11 6145,Albuquerque NM, Albuquerque, NM 87131 USA. EM sdavis@salud.unm.edu RI Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768 FU PHS HHS [U48/CCU610818-08] NR 27 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2007 VL 33 IS 1 SU 1 BP S1 EP S5 DI 10.1016/j.amepre.2007.04.004 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 187YD UT WOS:000247884300001 PM 17584588 ER PT J AU Helfrich, CD Savitz, LA Swiger, KD Weiner, BJ AF Helfrich, Christian D. Savitz, Lucy A. Swiger, Kathleen D. Weiner, Bryan J. TI Adoption and implementation of mandated diabetes registries by Community Health Centers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID INNOVATIONS AB Background: Innovations adopted by healthcare organizations are often externally mandated. However, few studies examine how mandated innovations progress from adoption to sustained effective use. This study uses Rogers's model of organizational innovation to explore community health centers' (CHCs') mandated adoption and implementation of disease registries in the federal Health Disparities Collaborative (HDC). Methods: Case studies were conducted on six CHCs in North Carolina participating in the HDC on type 2 diabetes mellitus. Data were collected from semistructured interviews with key staff, and from site-level and individual-level surveys. Results: Although disease registry adoption and implementation were mandated, CHCs exercised prerogative in the timing of registry adoption and the functions emphasized. Executive and medical director involvement, often directly on the HDC teams, was the single most salient influence on adoption and implementation. Staff members' personal experience with diabetes also provided context and gave registries added significance. Participants lauded HDC's technique of small-scale, rapid-cycle change, but valued even more shared problem solving and peer learning among HDC teams. However, lack of cross-training, inadequate resources, and staff turnover posed serious threats to sustainability of the registries. Conclusions: The present study illustrates the usefulness of Rogers's model for studying mandated innovation and highlights several key factors, including direct, personal involvement of organizational leadership, and shared problem solving and peer learning facilitated by the HDC. However, these six CHCs elected to participate early in the HDC, and may not be typical of North Carolina's remaining CHCs. Furthermore, most face important long-term challenges that threaten routinization. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA 98101 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Hlth Policy & Adm, Chapel Hill, NC USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98101 USA. RP Helfrich, CD (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv Res, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM christian.helfrich@va.gov RI Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768 FU NCCDPHP CDC HHS [U48-DP-000059]; PHS HHS [U48/CCU409660] NR 23 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2007 VL 33 IS 1 SU 1 BP S50 EP S65 DI 10.1016/j.amepre.2007.04.002 PG 16 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 187YD UT WOS:000247884300006 PM 17584591 ER PT J AU Weiner, BJ Helfrich, CD Savitz, LA Swiger, KD AF Weiner, Bryan J. Helfrich, Christian D. Savitz, Lucy A. Swiger, Kathleen D. TI Adoption and implementation of strategies for diabetes management in primary care practices SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CHRONIC ILLNESS; MODEL; QUALITY AB Background: Secondary and tertiary prevention of chronic illness is a major challenge for the United States healthcare system. Controlled studies show that interventions can enhance secondary prevention in primary care practices, but they shed little light on implementation of secondary prevention outside the experimental context. This study examines the adoption and implementation of an important set of secondary and tertiary prevention efforts-diabetes management strategies-for type 2 diabetes in the everyday clinical practice of primary care. It explores whether adoption and implementation processes differ by type of strategy or prevalence of diabetes among patients in the practice. Methods: Holistic case studies (those used to assess a single analytic unit, in this case, the physician group practice, as opposed to multiple embedded subunits) were conducted in 2001-2002 on six primary care practices in North Carolina identified from a statewide physician survey on strategies for diabetes management. Practices were selected by prevalence of diabetes and type of strategy for diabetes management-patient oriented (focused on self-management) versus biomedical (focused on secondary prevention practices). Results were derived from thematic analysis of interviews and secondary documents. Results: Adoption and implementation did not differ by diabetes prevalence or type of diabetes strategy. All practices had a routine forum for vetting new strategies, and most used traditional channels for identifying them. Implementation often required adaptation of the strategy and the organization. Sustained use of a diabetes strategy depended on favorable organizational policies and procedures (e.g., training,job redesign) and ongoing commitment of resources. Conclusions: Diabetes management strategies are often complex and require adoption and implementation processes different from those described by classic innovation diffusion models. Alternative conceptual models that consider organizational process, structure, and culture are needed. C1 Univ N Carolina, Hlth Policy & Adm, Chapel Hill, NC 27599 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Advocate Partners, Arlington, VA USA. RP Weiner, BJ (reprint author), Univ N Carolina, Hlth Policy & Adm, Chapel Hill, NC 27599 USA. EM Bryan_Weiner@unc.edu RI Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768 FU NCCDPHP CDC HHS [U48-DP-000059]; PHS HHS [U48/CCU409660] NR 34 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2007 VL 33 IS 1 SU 1 BP S35 EP S49 DI 10.1016/j.amepre.2007.04.001 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 187YD UT WOS:000247884300005 PM 17584590 ER PT J AU LaRowe, SD Myrick, H Hedden, S Mardikian, P Saladin, M McRae, A Brady, K Kalivas, PW Malcolm, R AF LaRowe, Steven D. Myrick, Hugh Hedden, Sarra Mardikian, Pascale Saladin, Michael McRae, Aimee Brady, Kathleen Kalivas, Peter W. Malcolm, Robert TI Is cocaine desire reduced by N-acetylcysteine? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEEKING AB objective: Animal models suggest that N-acetylcysteine inhibits cocaine-seeking. The present pilot study evaluated whether N-acetylcysteine would suppress reactivity to cocaine-related cues in cocaine-dependent humans. Method: in this double-blind, placebo-controlled trial, 15 participants received N-acetylcysteine or placebo during a 3-day hospitalization. Participants were crossed over to receive the opposite condition on a second, identical 3-day stay occurring 4 days later. During each hospital stay, participants completed a cue-reactivity procedure that involved collecting psychophysical and subjective data in response to slides depicting cocaine and cocaine use. Results: While taking N-acetylcysteine, participants reported less desire to use and less interest in response to cocaine slides and watched cocaine slides for less time. Conclusions: The inhibition of cocaine cue reactivity is consistent with existing preclinical data and supports the use of N-acetylcysteine as a treatment for cocaine dependence. C1 Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Informat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Rehabil Sci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Kalivas, PW (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403, Charleston, SC 29425 USA. EM kalivasp@musc.edu RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU NCRR NIH HHS [RR-01070]; NIDA NIH HHS [DA-015369, DA-018501, DA-07288] NR 6 TC 114 Z9 117 U1 0 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 JUL PY 2007 VL 164 IS 7 BP 1115 EP 1117 DI 10.1176/appi.ajp.164.7.1115 PG 3 WC Psychiatry SC Psychiatry GA 187TZ UT WOS:000247872700023 PM 17606664 ER PT J AU Sorensen, G Stoddard, AM Dubowitz, T Barbeau, EM Bigby, J Emmons, KM Berkman, LF Peterson, KE AF Sorensen, Glorian Stoddard, Anne M. Dubowitz, Tamara Barbeau, Elizabeth M. Bigby, JudyAnn Emmons, Karen M. Berkman, Lisa F. Peterson, Karen E. TI The influence of social context on changes in fruit and vegetable consumption: Results of the healthy directions studies SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CANCER PREVENTION; WORKING-CLASS; DIETARY CHANGE; MULTIETHNIC POPULATIONS; BLOOD-PRESSURE; NEIGHBORHOOD CHARACTERISTICS; COLORECTAL-CANCER; SMALL-BUSINESS; UNITED-STATES; HEART-DISEASE AB As part of the Harvard Cancer Prevention Program Project, we used a social contextual model of health behavior change to test an intervention targeting multiple risk-related behaviors in working-class, multiethnic populations. We examined the relationships between the social contextual factors in our conceptual model and changes in fruit and vegetable consumption from baseline to completion of intervention in health centers and small business studies. We analyzed change in fruit and vegetable consumption, measured at baseline and final assessments by self-report, in 2 randomized controlled prevention trials: 1 in small businesses (n=974) and 1 in health centers (n=1954). Stronger social networks, social norms that were more supportive, food sufficiency, and less household crowding were associated with greater change in fruit and vegetable intake. We also observed differences between our intervention sites. Social context can play an important role in promoting changes in fruit and vegetable consumption. C1 [Sorensen, Glorian; Barbeau, Elizabeth M.; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Sorensen, Glorian; Barbeau, Elizabeth M.; Emmons, Karen M.; Berkman, Lisa F.; Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Stoddard, Anne M.] New England Res Inst, Ctr Stat Anal & Res, Watertown, MA 02172 USA. [Dubowitz, Tamara] Univ Pittsburgh, Ctr Minor Hlth, Pittsburgh, PA USA. [Bigby, JudyAnn] Brigham & Womens Hosp, Off Women Family & Community Programs, Boston, MA 02115 USA. [Bigby, JudyAnn] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM glorian_sorensen@dfci.harvard.edu FU NCI NIH HHS [P01 CA075308, 5 P01 CA75308] NR 88 TC 58 Z9 59 U1 4 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2007 VL 97 IS 7 BP 1216 EP 1227 DI 10.2105/AJPH.2006.088120 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WJ UT WOS:000255647800012 PM 17538059 ER PT J AU Wittram, C Scott, JA AF Wittram, Conrad Scott, James A. TI F-18-FDG PET of pulmonary embolism SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; nuclear medicine; oncology; PET; pulmonary embolism ID CT; INFLAMMATION; TOMOGRAPHY; INFECTION AB OBJECTIVE. The purpose of this study was to describe the manifestations of pulmonary embolism on F-18-FDG PET scans in 13 patients. CONCLUSION. The activity of acute pulmonary embolism on FDG PET scans was significantly higher than the activity of vessels not containing thrombi. The shape of the abnormal FDG uptake may be focal or curvilinear. C1 Massachusetts Gen Hosp, Div Thorac Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Div Thorac Radiol, Founders 202,55 Fruit St, Boston, MA 02114 USA. EM cwittram@partners.org NR 18 TC 32 Z9 33 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2007 VL 189 IS 1 BP 171 EP 176 DI 10.2214/AJR.06.0640 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 183QU UT WOS:000247588100029 PM 17579168 ER PT J AU Soslow, RA Bissonnette, JP Wilton, A Ferguson, SE Alektiar, KM Duska, LR Oliva, E AF Soslow, Robert A. Bissonnette, John P. Wilton, Andrew Ferguson, Sarah E. Alektiar, Kaled M. Duska, Linda R. Oliva, Esther TI Clinicopathologic analysis of 187 high-grade endometrial carcinomas of different histologic subtypes: Similar outcomes belie distinctive biologic differences SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE high-grade endometrial carcinoma; grade 3 endometrioid; carcinoma; serous carcinoma; clear cell carcinoma; prognostic factors; outcome ID PAPILLARY-SEROUS-CARCINOMA; CLEAR-CELL CARCINOMA; PROGNOSTIC-SIGNIFICANCE; FIGO STAGE; SURVIVAL; CANCER; ADENOCARCINOMA; PARAMETERS; PATTERNS; FEATURES AB The clinical and histopathologic features of 187 high-grade endometrial cancers [FIGO grade 3 endometrioid (EC-3), serous (SC), and clear cell (CC)] were studied to determine whether clinicopathologic differences between these various histologic subtypes existed. The study group consisted of 89 EC-3s, 61 SCs, and 37 CCs. Treatment regimens were individualized. SCs and CCs were significantly more likely than EC-3s to occur in patients older than 65 years (P = 0.03), and SCs tended to occur more frequently in patients of African descent than EC-3s and CCs (P = 0.07), although this was not statistiattly significant. EC-3s had the highest rate of associated endometrial hyperplasia (P = 0.05). SCs were most likely to have high-stage disease at presentation (>= stage 1113; P = 0.01), with peritoncal dissernination at diagnosis being much more common compared with EC-3s and CCs (P = 0.004). Median follow-up was 39 months, and median overall survival was 47 months. Five-year survivals were 45% (EC-3), 36% (SC), and 50% (CC)-differences that were not statistically significant. In contrast, the impact of stage on survival was significant (P < 0.001). Among all other factors evaluated, only age greater than 65 years was a negative predictor (risk ratio, 2.23; P < 0.001), whereas a family history of cancer reduced the risk of death when controlling for stage (risk ratio, 0.54,- P = 0.005). When controlling for stage, race, reproductive history, personal history of cancer, histologic subtype, depth of myometrial invasion, lyruphovascular invasion, presence of an endometrial polyp, presence of hyperplasia, or staging adequacy did not affect prognosis. High-grade endometrial cancers of different histologic subtypes treated in an individualized manner are associated with similar clinical outcomes, but differences in age at presentation, race distribution, association with hyperplasia, stage, and sites of tumor dissemination support the idea that these represent distinct disease entities as defined by traditional histopathologic classification of endometrial cancers. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat & Cellular Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Gynecol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Pathobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gilette Ctr Womens Canc, Boston, MA 02114 USA. RP Soslow, RA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM soslowr@mskcc.org OI Soslow, Robert/0000-0002-7269-5898 NR 38 TC 76 Z9 78 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2007 VL 31 IS 7 BP 979 EP 987 DI 10.1097/PAS.0b013e31802ee494 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 183LG UT WOS:000247573700001 PM 17592263 ER PT J AU McCluggage, WG Young, RH AF McCluggage, W. Glenn Young, Robert H. TI Tubulo-squamous polyp - A report of ten cases of a distinctive hitherto uncharacterized vaginal polyp SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE vagina; polyp; immohistochemistry; prostatic acid phosphatase; prostate-specific antigen; differential diagnosis ID PROSTATE-SPECIFIC ANTIGEN; FEMALE GENITAL-TRACT; SUPERFICIAL CERVICOVAGINAL MYOFIBROBLASTOMA; SKENES GLAND ADENOCARCINOMA; ADENOID BASAL CARCINOMA; UTERINE CERVIX; ACID-PHOSPHATASE; BRENNER TUMOR; IMMUNOHISTOCHEMICAL ANALYSIS; UROTHELIAL DIFFERENTIATION AB We report 10 cases of a morphologically distinct vaginal polyp which has hitherto not been characterized. The Polyps Occurred in women aged 39 to 78 years (most were postmenopausal) and were from LO to 3.0cm. Most of whose location is known to us were in the upper vagina. Histologically, all the polyps were remarkably similar and composed of well-circurtiscribed expansile nests of epithelial cells embedded in a hypocellular fibrous stroma. The epithelial elements, which were morphologically bland, were predominantly glycogenated or nonglycogenated squamous in type but small tubules were present at the periphery of some of the nests in all cases. Some of the squamous nests exhibited central necrosis with or without calcification and, in 3 cases, some contained keratin pearls. In 3 cases, a few tubules unassociated with squamous elements were present. In 3 of 4 cases tested, the cells lining the tubules were positive with prostatic acid phosphatase and in 2 of 4 with prostate-specific antigen. The epithelial elements reacted with broad-spectrum cytokeratins and cytokeratin 7 but the mesenchymal component was negative. The squamous elements were estrogen receptor positive and the mesenchymal component estrogen and progesterone receptor positive. The histologic features of this polyp, which we term "tubulo-squamous polyp of the vagina," are constant and distinctive and differ from other polyps and from mixed tumor of the vagina. Several cases reported in the literature as vaginal mixed tumor or Brenner tumor are likely examples of this entity. Possible theories of histogenesis include a Mullerian origin, derivation from mesonephric remnants or derivation from urogenital sinus-derived epithelium. Positive staining in some cases with prostatic acid phosphatase and prostate-specific antigen raises the possibility of ectopic prostatic tissue, although the overall appearance is different from that entity, or derivation from paraurethral Skene glands, the female equivalent of prostatic glands in the male. C1 Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. EM glenn.mccluggage@bll.n-i.nhs.uk NR 39 TC 19 Z9 19 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 JUL PY 2007 VL 31 IS 7 BP 1013 EP 1019 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 183LG UT WOS:000247573700005 PM 17592267 ER PT J AU Bacon, CM Ye, HT Diss, TC McNamara, C Kueck, B Hasserjian, RP Rohatiner, AZS Ferry, J Du, MQ Dogan, A AF Bacon, Chris M. Ye, Hongtao Diss, Timothy C. McNamara, Christopher Kueck, Brian Hasserjian, Robert P. Rohatiner, Ama Z. S. Ferry, Judith Du, Ming-Qing Dogan, Ahmet TI Primary follicular lymphoma of the testis and epididymis in adults SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE follicular lymphoma; testis; epididymis; adult ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; MALT LYMPHOMAS; GRADE 3B; EXPRESSION; CHILDHOOD; DISEASE; ENTITY; IMMUNOPHENOTYPE AB Primary testicular lymphomas typically occur in patients over 60 years of age. Most are diffuse large B-Cell lymphomas with frequent dissemination and a poor prognosis. Primary follicular lymphoma of the adult testis has not been well characterized. However, a small number of primary testicular follicular lymphomas have recently been described in children. These showed stage IE disease.. a lack of BCL2 gene rearrangement and Bcl-2 protein expression, and a good clinical outcome. Here, we describe 5 cases of primary follicular lymphoma of the testis and epididymis in adults. These presented as unilateral testicular masses 12 to 40 mm in diameter and were characterized histologically by small neoplastic follicles in a sclerotic background. The neoplastic cells expressed CD10 and Bcl-6, but not Bcl-2 and lacked t(14;18)(q32;q21)/IGH-BCL2 and BCL6 gene rearrangements. Four of the five patients were 35 years old or younger, and 4 presented with stage 1EA disease. Although follow-up is 12 months or less in 2 of the 5 patients, to date each has followed an indolent clinical course. These features are different from those of most adult nodal follicular lymphomas but are very similar to those of the pediatric primary testicular follicular lymphoinas. Together, the pediatric and adult cases represent a discrete clinicopathologic entity of t(14;18)(q32;q21)/IGH-BCL2-negative primary follicular lymphoma of the testis and epididymis, which typically present as clinically indolent localized disease in young males and should be distinguished from the diffuse large B-cell lymphoma more frequently seen in the testes of older adults. C1 Univ Cambridge, Div Mol Histopathol, Dept Pathol, Cambridge CB2 2QQ, England. St Bartholomews Hosp, Dept Med Oncol, London, England. Waukesha Mem Hosp, Dept Pathol, Waukesha, WI USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Bacon, CM (reprint author), Univ Cambridge, Div Mol Histopathol, Dept Pathol, Box 231,Level 3 Lab Block, Cambridge CB2 2QQ, England. EM cmb82@cam.ac.uk NR 49 TC 23 Z9 25 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 JUL PY 2007 VL 31 IS 7 BP 1050 EP 1058 DI 10.1097/PAS.0b013e31802ee4ab PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 183LG UT WOS:000247573700010 PM 17592272 ER PT J AU Fagenholz, PJ Castillo, CF Harris, NS Pelletier, AJ Camargo, CA AF Fagenholz, Peter J. Del Castillo, Carlos Fernandez Harris, N. Stuart Pelletier, Andrea J. Camargo, Carlos A., Jr. TI Increasing United States hospital admissions for acute pancreatitis, 1988-2003 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE pancreatitis; epidemiology; United States ID MORTALITY; ETIOLOGY; MANAGEMENT; DISEASE; TRENDS; EPIDEMIOLOGY; POPULATION; OBESITY; COUNTY AB PURPOSE: To examine the epidemiology of hospital admissions for acute pancreatitis in the United States. METHODS: We compiled data from the 1988-2003 National Hospital Discharge Survey and analyzed it with respect to patient demographics, hospital type and region, procedures performed, length of hospital stay, and inpatient mortality. RESULTS: Hospital admissions for acute pancreatitis increased from a 1988 low of 101,000 (95% confidence interval [Cl]: 87,000-116,000) to a 2002 peak of 210,000 (95% Cl: 186,000-234,000). The corresponding admission rate increased from 0.4 to 0.7 hospitalizations per 1000 U.S. population (p = 0.001). The patients' average age was 53 years, 51% were male, and 23% were black. The hospitalization rate was higher among blacks (0.9; 95% Cl, 0.6-1.1) than among whites (0.4; 95% Cl, 0.3-0.5). The mean length of stay was 6.9 days and decreased over the study period. Overall mortality was 2%, with increasing age and mate gender comprising independent risk factors for death. CONCLUSIONS: The hospitalization rate for acute pancreatitis in the United States is rising and is higher in blacks than in whites. Further research is necessary to identify the cause(s) of increasing pancreatitis admissions, the observed racial disparity, and the cost of these admissions. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 47 TC 124 Z9 127 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2007 VL 17 IS 7 BP 491 EP 497 DI 10.1016/j.annepidem.2007.02.002 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 187ZV UT WOS:000247888900001 PM 17448682 ER PT J AU Bass, E French, DD Bradham, DD Rubenstein, LZ AF Bass, Elizabeth French, Dustin D. Bradham, Douglas D. Rubenstein, Laurence Z. TI Risk-adjusted mortality rates of elderly veterans with hip fractures SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE hip fractures; risk adjusted; survival analysis; mortality; veterans ID QUALITY-OF-LIFE; NATIONAL VETERANS; OUTPATIENT MEDICATION; COMORBIDITY MEASURES; ADMINISTRATIVE DATA; THIAZIDE DIURETICS; FUNCTIONAL STATUS; GREATER RISK; OLDER-ADULTS; MEN AB PURPOSE: The goal of this research was to estimate 12-month survival rates for a large sample of elderly veterans after hip fracture with a risk-adjusted model and to compare the results of men to those of women. METHODS: The study design was a retrospective, secondary data analysis of national Veterans Health Administration (VHA) Medicare beneficiaries. The study population was 43,165 veterans with hip fracture first admitted to a Medicare-eligible facility during our specified enrollment period of 1999-2002. Measurement was a Cox proportional hazard model or survival analysis of hip fracture patients with an outcome of death over a I year period after discharge controlled by age, gender, and selected Elixhauser comorbidities. RESULTS: The unadjusted, I year mortality rates (30 days = 9.7%, 90 days = 17.5%, 180 days = 24%, 365 days = 32.2%) were slightly higher than the adjusted rates (30 days = 8.9%, 90 days = 15.6%, 180 days = 21.8%, 1 year = 29.9%). The mortality odds for women 12 months after hip fracture were 18%, compared with 32% for men. The comorbidity adjustment suggested that the presence of metastatic cancer increased the risk of death by almost 4 times compared with those patients without this diagnosis. Other particularly high-risk conditions included congestive heart failure, renal failure, liver disease, lymphoma, and weight loss, each of which increased the 1 year mortality risk by approximately two-fold. CONCLUSIONS: One in 3 elderly male veterans who sustain a hip fracture dies within I year. Our work represents the first large study of hip fractures with a predominantly male sample and confirms that men have a higher mortality risk than women, as reported by previous researchers who used smaller samples that were mostly female. Fracture patients with metastatic cancer, renal failure, lymphoma, weight loss, and liver disease have higher mortality risks. The adverse outcomes associated with hip fracture argue for clinical intervention strategies, such as gait and balance testing, and osteoporosis diagnosis that may prevent fractures in both genders. C1 James A Haley Vet Affairs Med Ctr, VISN Patient Safety Ctr Inquiry 8, Tampa, FL 33612 USA. Cooperat Studies Program Coordinating Ctr Perry P, Perry Point, MD USA. Univ Maryland, Dept Epidemiol & Prevent Med, College Pk, MD 20742 USA. Univ Calif Berkeley, Sch Med, Berkeley, CA 94720 USA. Vet Affairs Greater Los Angeles Healthcare Syst G, Educ & Clin Ctr, Sepulveda & W Los Angles Div, Los Angeles, CA USA. RP Bass, E (reprint author), James A Haley Vet Affairs Med Ctr, VISN Patient Safety Ctr Inquiry 8, 13000 Bruce B Downs Blvd 118M, Tampa, FL 33612 USA. EM Elizabeth.Bass@va.gov OI French, Dustin/0000-0003-4064-3206 NR 47 TC 104 Z9 110 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2007 VL 17 IS 7 BP 514 EP 519 DI 10.1016/j.annepidem.2006.12.004 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 187ZV UT WOS:000247888900005 PM 17420142 ER PT J AU Chun, LS Samii, A Hutter, CM Griffith, A Roberts, JW Leis, BC Mosley, AD Wander, L Edwards, KL Payami, H Zabetian, CP AF Chun, Lani S. Samii, Ali Hutter, Carolyn M. Griffith, Alida Roberts, John W. Leis, Berta C. Mosley, Anthony D. Wander, Luke Edwards, Karen L. Payami, Haydeh Zabetian, Cyrus P. TI DBH-1021C -> T does not modify risk or age at onset in Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID DOPAMINE-BETA-HYDROXYLASE; LOCUS-COERULEUS LESIONS; PARKINSONS-DISEASE; FUNCTIONAL POLYMORPHISM; COMPLEX DISEASES; SUBSTANTIA-NIGRA; ASSOCIATION; TRAITS; GENEPD; SCAN AB DBH is a candidate gene in Parkinson's disease (PD) and contains a putative functional polymorphism (-1021C -> T) that has been reported to modify PD susceptibility. We examined -1021C -> T in a sample of 1,244 PD patients and 1,186 unrelated control subjects. There was no significant difference in allele (p = 0.14) or genotype (p = 0.26) frequencies between the two groups. A similar result was obtained after pooling our data with those previously published. Furthermore, we found no evidence for an effect of genotype on age at onset among patients. Our Findings argue against DBH -1021C -> T as a risk factor or age at onset modifier in PD. C1 Geriatr Res Educ, Seattle, WA 98108 USA. VA Puget Sound Health Care Syst, Clin Ctr S 182, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. VA Puget Sound Health Care Syst, Parkinsons Dis Res Educ, Seattle, WA USA. VA Puget Sound Health Care Syst, Clin Ctr, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA 98034 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY USA. VA Puget Sound Hlth Care Syst, Clin Ctr, Seattle, WA USA. RP Zabetian, CP (reprint author), Geriatr Res Educ, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306; Wander, Pandora/0000-0003-3671-1464 FU NIA NIH HHS [P30 AG 008017, P30 AG008017, U24 AG021886]; NINDS NIH HHS [K08 NS 044138, K08 NS044138, K08 NS044138-04, R01 NS 036960, R01 NS036960] NR 18 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2007 VL 62 IS 1 BP 99 EP 101 DI 10.1002/ana.21149 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 199CF UT WOS:000248673100017 PM 17503507 ER PT J AU Goldhirsch, A Wood, WC Gelber, RD Coates, AS Thurlimann, B Senn, HJ Members, P AF Goldhirsch, A. Wood, W. C. Gelber, R. D. Coates, A. S. Thuerlimann, B. Senn, H.-J. Members, Panel TI Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007 SO ANNALS OF ONCOLOGY LA English DT Article ID OF-CLINICAL-ONCOLOGY; CARCINOMA-IN-SITU; BRCA2 MUTATION CARRIERS; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; RECEPTOR STATUS; FOLLOW-UP; RADIOTHERAPY; EXPRESSION AB The 10(th) St Gallen (Switzerland) expert consensus meeting in March 2007 refined and extended a target-oriented approach to adjuvant systemic therapy of early breast cancer. Target definition is inextricably intertwined with the availability of target-specific therapeutic agents. Since 2005, the presence of HER2 on the cell surface has been used as an effective target for trastuzumab much as steroid hormone receptors are targets for endocrine therapies. An expert Panel reaffirmed the primary importance of determining endocrine responsiveness of the cancer as a first approach to selecting systemic therapy. Three categories were acknowledged: highly endocrine responsive, incompletely endocrine responsive and endocrine non-responsive. The Panel accepted HER2-positivity to assign trastuzumab, and noted that adjuvant trastuzumab has only been assessed together with chemotherapy. They largely endorsed previous definitions of risk categories. While recognizing the existence of several molecularly-based tools for risk stratification, the Panel preferred to recommend the use of high-quality standard histopathological assessment for both risk allocation and target identification. Chemotherapy, although largely lacking specific target information, is the only option in cases which are both endocrine receptor-negative and HER2-negative. Chemotherapy is conventionally given with or preceding trastuzumab for patients with HER2-positive disease, and may be used for patients with endocrine responsive disease in cases where the sufficiency of endocrine therapy alone is uncertain. Recommendations are provided not as specific therapy guidelines but rather as a general guidance emphasizing main principles for tailoring therapeutic choice. C1 European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy. Oncol Inst So Switzerland, Int Breast Canc Study Grp, CH-6500 Bellinzona, Switzerland. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Sydney, Sydney, NSW 2006, Australia. Int Breast Canc Study Grp, Sydney, NSW 2006, Australia. Kantonsspital, Div Gynecol Oncol, CH-9006 St Gallen, Switzerland. Tumor Ctr ZeTuP, CH-9006 St Gallen, Switzerland. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org NR 95 TC 582 Z9 615 U1 3 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2007 VL 18 IS 7 BP 1133 EP 1144 DI 10.1093/annonc/mdm271 PG 12 WC Oncology SC Oncology GA 211YG UT WOS:000249559600002 PM 17675394 ER PT J AU Correa, DD Maron, L Harder, H Klein, M Armstrong, CL Calabrese, P Brornberg, JEC Abrey, LE Batchelor, TT Schiff, D AF Correa, D. D. Maron, L. Harder, H. Klein, M. Armstrong, C. L. Calabrese, P. Brornberg, J. E. C. Abrey, L. E. Batchelor, T. T. Schiff, D. TI Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines SO ANNALS OF ONCOLOGY LA English DT Review DE chemotherapy; cognitive; neurotoxicity; primary CNS lymphoma; radiotherapy ID PRIMARY CNS LYMPHOMA; QUALITY-OF-LIFE; ENHANCED CHEMOTHERAPY DELIVERY; BRAIN-BARRIER DISRUPTION; HIGH-DOSE METHOTREXATE; INTRAVENTRICULAR CHEMOTHERAPY; PHASE-II; DEFERRED RADIOTHERAPY; EUROPEAN-ORGANIZATION; CLINICAL-TRIALS AB Background: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. Design: In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. Results: The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome, On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. Conclusion: The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Dr Daniel Den Hoed Canc Ctr, Dept Neurooncol, NL-3008 AE Rotterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Med Psychol, Amsterdam, Netherlands. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Ruhr Univ Bochum, Dept Neurol, D-4630 Bochum, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Virginia, Hlth Sci Ctr, Div Neurooncol, Charlottesville, VA USA. RP Correa, DD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM corread@mskcc.org RI Klein, Martin/C-4192-2012 OI Klein, Martin/0000-0003-4160-5746 NR 50 TC 76 Z9 76 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2007 VL 18 IS 7 BP 1145 EP 1151 DI 10.1093/annonc/mdl464 PG 7 WC Oncology SC Oncology GA 211YG UT WOS:000249559600003 PM 17284616 ER PT J AU Meyerhardt, JA Stuart, K Fuchs, CS Zhu, AX Earle, CC Bhargava, P Blaszkowsky, L Enzinger, P Mayer, RJ Battu, S Lawrence, C Ryan, DP AF Meyerhardt, J. A. Stuart, K. Fuchs, C. S. Zhu, A. X. Earle, C. C. Bhargava, P. Blaszkowsky, L. Enzinger, P. Mayer, R. J. Battu, S. Lawrence, C. Ryan, D. P. TI Phase II study of FOLFOX, bevacizumab and erlotinib as first-line therapy for patients with, metastastic colorectal cancer SO ANNALS OF ONCOLOGY LA English DT Article DE bevacizumab; colorectal cancer; erlotinib; FOLFOX ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; PLUS IRINOTECAN; LEUCOVORIN; CETUXIMAB; TRIAL; FLUOROURACIL; MALIGNANCIES; OXALIPLATIN; GEFITINIB AB Background: Targeting the epidermal growth factor receptor and angiogenesis have proven useful strategies against metastatic colorectal cancer. The benefit of combining inhibitors of both pathways is unknown. Patients and methods: Patients with previously untreated metastatic colorectal cancer were enrolled in a phase 11 trial of infusional 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), bevacizumab and erlotinib. The primary end point was progression-free survival. Results: Thirty-five patients were enrolled and all came off trial for reasons other than progression; 18 (51%) had protocol-defined adverse events requiring removal, nine (26%) withdrew consent due to toxicity, six pursued surgery or localized therapies and two requested a treatment holiday. Principal toxic effects included rash, neuropathy and diarrhea. Seven patients came off trial before first restaging. By intention-to-treat analysis, one patient had a confirmed complete response, 10 had confirmed partial responses and one had an unconfirmed partial response (response rate = 34%). One patient had progressive disease at time of withdrawal from the trial, thus progression-free survival could not be calculated. Conclusion: The combination of FOLFOX, bevacizumab and erlotinib led to higher than expected early withdrawal due to toxicity, limiting conclusions regarding efficacy. These findings raise concern regarding the tolerability of adding more agents to already complex combination regimens for metastatic colorectal cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Med Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jmeyerhardt@partners.org NR 27 TC 50 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2007 VL 18 IS 7 BP 1185 EP 1189 DI 10.1093/annonc/mdm124 PG 5 WC Oncology SC Oncology GA 211YG UT WOS:000249559600009 PM 17483115 ER PT J AU Leonard, JP Friedberg, JW Younes, A Fisher, D Gordon, LI Moore, J Czuczman, M Miller, T Stiff, P Cheson, BD Forero-Torres, A Chieffo, N McKinney, B Finucane, D Molina, A AF Leonard, J. P. Friedberg, J. W. Younes, A. Fisher, D. Gordon, L. I. Moore, J. Czuczman, M. Miller, T. Stiff, P. Cheson, B. D. Forero-Torres, A. Chieffo, N. McKinney, B. Finucane, D. Molina, A. TI A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma SO ANNALS OF ONCOLOGY LA English DT Article DE galiximab; lymphoma; monoclonal antibody; rituximab; CD80 ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; REED-STERNBERG CELLS; IN-VIVO EXPRESSION; COSTIMULATORY MOLECULES; THERAPY; SURVIVAL; DISEASE; CD86; PROLIFERATION AB Background: Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin's lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety, pharmacokinetics, and efficacy were evaluated. Patients and methods: Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractory patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m(2)) and rituximab (375 mg/m(2)). International Workshop Response Criteria (IWRC) were used to evaluate response. Results: Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%:19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics. Conclusion: These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated. C1 Cornell Univ, Weill Med Coll, Div Hematol Oncol, New York, NY 10021 USA. New York Presbyterian Hosp, New York, NY 10021 USA. Univ Rochester, James P Wilmot Canc Ctr, Lymphoma Clin Res, Rochester, NY USA. MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma & Myeloma, Houston, TX USA. Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. Duke Univ, Div Hematol Oncol, Durham, NC USA. Roswell Pk Canc Inst, Dept Hematol Oncol & Bone Marrow Transplantat, Buffalo, NY 14263 USA. Univ Arizona, Hematol Oncol Sect, Tucson, AZ USA. Loyola Univ, Div Hematol Oncol, Med Ctr, Chicago, IL 60611 USA. Georgetown Univ Hosp, Dept Hematol, Washington, DC 20007 USA. Univ Alabama, Div Hematol Oncol, Birmingham, AL 35294 USA. Biogen Idec Inc, Dept Hematol Oncol, Med Res, San Diego, CA USA. Biogen Idec Inc, Dept Biostat, San Diego, CA USA. Biogen Idec Inc, Dept Med Writing, San Diego, CA USA. RP Leonard, JP (reprint author), Cornell Univ, Weill Med Coll, Div Hematol Oncol, Starr Bldg,Room 340,520 E 70th St, New York, NY 10021 USA. EM jpleonar@med.cornell.edu OI Gordon, Leo/0000-0003-1666-7064 NR 26 TC 73 Z9 76 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2007 VL 18 IS 7 BP 1216 EP 1223 DI 10.1093/annonc/mdm114 PG 8 WC Oncology SC Oncology GA 211YG UT WOS:000249559600014 PM 17470451 ER PT J AU Zeitels, SM AF Zeitels, Steven M. TI Chevalier Jackson Lecture 2006 - Concepts and culture of innovation SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehab, One Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 2007 VL 116 IS 7 BP 479 EP 482 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 192AZ UT WOS:000248174400001 PM 17727077 ER PT J AU Merchant, SN Nakajima, HH Halpin, C Nadol, JB Lee, DJ Innis, WP Curtin, H Rosowski, JJ AF Merchant, Saumil N. Nakajima, Hideko H. Halpin, Christopher Nadol, Joseph B., Jr. Lee, Daniel J. Innis, William P. Curtin, Hugh Rosowski, John J. TI Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE air-bone gap; audiometry; conductive hearing loss; large vestibular aqueduct syndrome ID CONDUCTIVE HEARING-LOSS; SEMICIRCULAR CANAL DEHISCENCE; EVOKED MYOGENIC POTENTIALS; TYMPANIC MEMBRANE; MIDDLE-EAR; INNER-EAR; CHINCHILLA; FIXATION AB Objectives: Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap. Methods: Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears. Results: One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in I of the 2 ears tested, and exploratory tympanotomy in I case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound. Conclusions: We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non-middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air-bone gap at low frequencies. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Boston Med Ctr, Dept Otolaryngol, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Massachusetts, Mem Med Ctr, Dept Surg, Div Otolaryngol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC004798, R01 DC004798-07, R01 DC04798] NR 28 TC 47 Z9 55 U1 2 U2 8 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 2007 VL 116 IS 7 BP 532 EP 541 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 192AZ UT WOS:000248174400009 PM 17727085 ER PT J AU Weinand, C Gupta, R Weinberg, E Madisch, I Jupiter, JB Vacanti, JP AF Weinand, Christian Gupta, Rajiv Weinberg, Eli Madisch, Ijad Jupiter, Jesse B. Vacanti, Joseph P. TI Human shaped thumb bone tissue engineered by Hydrogel-beta-tricalciumphosphate/poly-epsilon-caprolactone scaffolds and magnetically sorted stem cells SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY NOV 30-DEC 03, 2006 CL Boston, MA SP NE Soc Plastic Surg DE tissue engineering; thumb; bone; reconstruction; hMSCs; CD 133+; magnetically cell sorting ID MARROW STROMAL CELLS; CALVARIAL DEFECTS; IN-VIVO; TRANSPLANTATION; REPLANTATION; REPAIR; RECONSTRUCTION; FIBROBLASTS; POLYMER; PHALANX AB Traumatic amputation of a thumb with bone loss leaves a patient in severe disability. Reconstructive procedures are restricted by limited shape and have the disadvantage of severe donor-site morbidity. To overcome these limitations, we used a tissue engineering approach to create a distal thumb bone phalanx, combining magnetically sorted 133+ human mesenchymal stem cells (hMSCs) suspended in successful tested hydrogels for bone formation and porous 3-dimensionally printed scaffolds (3DP) in the shape of a distal thumb bone phalanx. Collagen 1 and fibrin glue hydrogels with suspended hMSCs were first histologically evaluated in vitro for bone formation after 6 weeks. Then 3DP scaffolds, made from a mix of osteoinductive and -conductive beta-tricalciumphosphate (beta-TCP) and poly-epsilon-caprolactone (PCL), with hydrogels and suspended hMSCs, were implanted into nude mice subcutaneously for 15 weeks, Histologic evaluation, high-resolution volumetric CT (VCT) scanning, and biomechanical testing confirmed formation of bonelike tissue. Both hydrogels with CD 133+ hMSCs on 3DP scaffolds supported bone formation. Collagen 1 resulted in radiologically better bone formation. Bone tissue can be successfully tissue engineered with CD 133+ hMSCs, collagen 1 hydrogels, and porous 3DP beta-TCP/PCL scaffolds. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Exterm Serv, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA USA. RP Vacanti, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Tissue Engn & Organ Fabricat, Warren 11-1157,55 Fruit St, Boston, MA 02114 USA. EM JVacanti@Partners.org NR 37 TC 9 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUL PY 2007 VL 59 IS 1 BP 46 EP 52 DI 10.1097/01.sap.0000264887.30392.72 PG 7 WC Surgery SC Surgery GA 182IX UT WOS:000247499400015 PM 17589259 ER PT J AU Crippa, S Bassi, C Warshaw, AL Falconi, M Partelli, S Thayer, SP Pederzoli, P Fernandez-del Castillo, C AF Crippa, Stefano Bassi, Claudio Warshaw, Andrew L. Falconi, Massimo Partelli, Stefano Thayer, Sarah P. Pederzoli, Paolo Fernandez-del Castillo, Carlos TI Middle pancreatectomy - Indications, short- and long-term operative outcomes SO ANNALS OF SURGERY LA English DT Article ID PAPILLARY MUCINOUS NEOPLASMS; MEDIAL PANCREATECTOMY; PANCREAS; COMPLICATIONS; SURGERY; RESECTION; TUMORS; NECK; DEFINITION; MANAGEMENT AB Objective: To evaluate the indications, perioperative, and long-term outcomes of a large cohort of patients who underwent middle pancreatectomy (MP). Summary Background Data: MP is a parenchyma-sparing technique aimed to reduce the risk of postoperative exocrine and endocrine insufficiency. Reported outcomes after MP are conflicting. Methods: Patients who underwent MP between 1990 and 2005 at the Massachusetts General Hospital and at the University of Verona were identified. The outcomes after MP were compared with a control group that underwent extended left pancreatectomy (ELP) for neoplasms in the mid pancreas. Results: A total of 100 patients underwent MP. The most common indications were neuroendocrine neoplasms, serous cystadenoma, and branch-duct IPMNs. Comparison with 45 ELP showed that intraoperative blood loss and transfusions were significantly higher for ELP. The 2 groups showed no differences in overall morbidity, abdominal complications, overall pancreatic fistula, and grade B/C pancreatic fistula rate (17% in MP and 13% in ELP), but the mean hospital-stay was longer for MP patients (P = 0.005). Mortality was zero. In the MP group, 5 patients affected by IPMNs had positive resection margins and 3 had recurrence. After a median follow-up of 54 months, incidence of new endocrine and exocrine insufficiency were significantly higher in the ELP group (4% vs. 38%, P = 0.0001 and 5% vs. 15.6%, P = 0.039, respectively). Conclusions: MP is a safe and effective procedure for treatment of benign and low-grade malignant neoplasms of the mid pancreas and is associated with a low risk of development of exocrine and endocrine insufficiency. MP should be avoided in patients affected by main-duct IPMN. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Wang Ambulatory Care Ctr 336, Boston, MA 02114 USA. Univ Verona, Policlin GB Rossi, Dept Surg, I-37100 Verona, Italy. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Wang Ambulatory Care Ctr 336, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org OI Falconi, Massimo/0000-0001-9654-7243 NR 35 TC 116 Z9 130 U1 0 U2 4 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 JUL PY 2007 VL 246 IS 1 BP 69 EP 76 DI 10.1097/01.sla.0000262790.51512.57 PG 8 WC Surgery SC Surgery GA 184WC UT WOS:000247672300012 PM 17592293 ER PT J AU Reginato, AM AF Reginato, A. M. TI Genetics of gout SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Reginato, A. M.] Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 22 EP 22 PG 1 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101100074 ER PT J AU Kay, J Matteson, EL Dasgupta, B Nash, P Durez, P Hall, S Hsia, EC Chiruvolu, P Han, J Rahman, MU AF Kay, J. Matteson, E. L. Dasgupta, B. Nash, P. Durez, P. Hall, S. Hsia, E. C. Chiruvolu, P. Han, J. Rahman, M. U. TI Improvement in DAS28 response through one-year of golimumab treatment in patients with active RA despite treatment with methotrexate: A phase II, randomized, double blind, placebo controlled, dose ranging trial SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Kay, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Matteson, E. L.] Mayo Coll Med, Rochester, MN USA. [Dasgupta, B.] Southend Hosp, Southampton, Hants, England. [Durez, P.] Clin Univ St Luc, B-1200 Brussels, Belgium. [Hall, S.] Cabrini Med Ctr, Melbourne, Vic, Australia. [Chiruvolu, P.; Han, J.] Centocor Res & Dev Inc, Malvern, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 175 EP 176 PG 2 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101100561 ER PT J AU Ibrahim, SA Groeneveld, RW Mor, M Geng, M Kwoh, K AF Ibrahim, S. A. Groeneveld, R. W. Mor, M. Geng, M. Kwoh, K. TI Trust in physicians as a predictor of preference for total joint replacement SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Ibrahim, S. A.; Mor, M.; Geng, M.; Kwoh, K.] Univ Pittsburgh, Sch Med, VA CHERP, Pittsburgh, PA USA. [Groeneveld, R. W.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 262 EP 262 PG 1 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101101117 ER PT J AU Ibrahim, SA Groeneveld, PW Maria, M Ming, G Kwoh, K AF Ibrahim, S. A. Groeneveld, P. W. Maria, M. Ming, G. Kwoh, K. TI Preference for joint replacement and relationship with patient rated quality of life or disease severity SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Ibrahim, S. A.; Maria, M.; Ming, G.; Kwoh, K.] Univ Pittsburgh, Sch Med, VA CHERP, Pittsburgh, PA 15260 USA. [Groeneveld, P. W.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 263 EP 263 PG 1 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101101118 ER PT J AU Visvanathan, S Rojas, J Wagner, C Kay, J Dasgupta, B Matteson, EL Mack, M Gathany, T Baker, DG Rahman, MU AF Visvanathan, S. Rojas, J. Wagner, C. Kay, J. Dasgupta, B. Matteson, E. L. Mack, M. Gathany, T. Baker, D. G. Rahman, M. U. TI Decreases in E-selectin, IL-18, SAA, and MMP-9 may predict clinical response to golimumab plus MTX therapy in rheumatoid arthritis patients SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Visvanathan, S.; Wagner, C.] Centocor Res & Dev Inc, Clinical Pharmacol, Malvern, Worcs, England. [Rojas, J.] Centocor Res & Dev Inc, Technol Licensing, Malvern, Worcs, England. [Kay, J.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Dasgupta, B.] Southland Hosp, Dept Rheumatol, Westcliff S E, England. [Matteson, E. L.] Mayo Coll Med, Rochester, MN USA. [Gathany, T.] Centoor Res & Dev, Outcomes Res, Malvern, PA USA. [Baker, D. G.] Centoor Res & Dev, Clin Res, Malvern, PA USA. [Rahman, M. U.] Centoor Res & Dev, Immunol Clin Res, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 340 EP 340 PG 1 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101101365 ER PT J AU Laine, L Curtis, SP Cryer, B Zhang, Y Cannon, CP AF Laine, L. Curtis, S. P. Cryer, B. Zhang, Y. Cannon, C. P. TI Risk factors for NSAID-associated upper GI clinical events in a long-term double-blind study of 34,701 arthritis patients SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Laine, L.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Curtis, S. P.; Zhang, Y.] Merck Res Labs, Rahway, NJ USA. [Cryer, B.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Cannon, C. P.] TIMI Study Grp, Div Cardiovasc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 501 EP 501 PG 1 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101102133 ER PT J AU Laine, L Curtis, SP Langman, M Jensen, D Cryer, B Zhu, H Cannon, CP AF Laine, L. Curtis, S. P. Langman, M. Jensen, D. Cryer, B. Zhu, H. Cannon, C. P. TI Lower GI clinical events in a double-blind randomized comparison of a COX-2 selective inhibitor (etoricoxib) and a traditional NSAID (diclofenac) in 34,701 arthritis patients SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2007) CY JUN 13-16, 2007 CL Barcelona, SPAIN SP European League Against Rheumatism C1 [Laine, L.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Curtis, S. P.; Zhu, H.] Merck Res Labs, Rahway, NJ USA. [Langman, M.] Univ Birmingham, Dept Med, Birmingham B15 2TT, W Midlands, England. [Jensen, D.] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA 90024 USA. [Cryer, B.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Cannon, C. P.] TIMI Study Grp, Div Cardiovasc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2007 VL 66 SU 2 BP 502 EP 502 PG 1 WC Rheumatology SC Rheumatology GA 261SU UT WOS:000253101102134 ER PT J AU Nieder, C Astner, ST Molls, M Grosu, AL AF Nieder, Carsten Astner, Sabrina T. Molls, Michael Grosu, Anca L. TI Analysis of long-term survivors of glioblastoma multiforme in a single institution with aggressive local retreatment protocol SO ANTICANCER RESEARCH LA English DT Article DE radiotherapy; chemotherapy; neurosurgery; glioblastoma; glioma; retreatment ID NEWLY-DIAGNOSED GLIOBLASTOMA; PHASE-II; RADIATION-THERAPY; MALIGNANT GLIOMA; ADULT PATIENTS; TEMOZOLOMIDE; RADIOTHERAPY; CHEMOTHERAPY; ACID AB Current treatment methods result in survival beyond 2 years in just a minority of adult patients with glioblastoma multiforme (GBM). Our institution has used an aggressive policy of local retreatment, including surgery and radiotherapy, at first relapse. Long-term survival (>2 years) after such an approach was evaluated. Patients and Methods: A retrospective analysis was carried out of all patients with confirmed histological diagnosis of GBM at relapse. Patients with oligodendroglial component or progression from low-grade glioma were not included. Results: Out of the 30 patients managed with aggressive local retreatment, 8 survived for more than 2 years, but no 5-year survivors were observed. All were younger than 60 years, had a good performance status, RPA class III or IV and a long interval to relapse. Those with the longest survival times had also received two different chemotherapy regimens. However, two of the patients were never treated with chemotherapy. Survival from retreatment was 5-17 months. Conclusion: When selecting patients on the basis of the factors associated with long-term survival, the same sequence of surgery, radiotherapy and chemotherapy that should be considered at first diagnosis might provide a moderate survival extension. C1 Nordlandssykenhuset HF, Radiat Oncol Unit, Dept Internal Med, N-8092 Bodo, Norway. Tech Univ Munich, Klinikum Rechts Isar, Dept Radiat Oncol, D-81675 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA USA. RP Nieder, C (reprint author), Nordlandssykenhuset HF, Radiat Oncol Unit, Dept Internal Med, N-8092 Bodo, Norway. EM carsten.nieder@nlsh.no NR 20 TC 5 Z9 5 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2007 VL 27 IS 4C BP 2993 EP 2996 PG 4 WC Oncology SC Oncology GA 197HV UT WOS:000248546100069 PM 17695484 ER PT J AU Almyroudis, NG Sutton, DA Fothergill, AW Rinaldi, MG Kusne, S AF Almyroudis, Nikolaos G. Sutton, Deanna A. Fothergill, Annette W. Rinaldi, Michael G. Kusne, Shimon TI In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CARE CANCER CENTER; AMPHOTERICIN-B; FILAMENTOUS FUNGI; DISSEMINATED ZYGOMYCOSIS; ASPERGILLUS SPP.; SALVAGE THERAPY; POSACONAZOLE; ITRACONAZOLE; VORICONAZOLE; CASPOFUNGIN AB We evaluated the in vitro susceptibilities of 217 zygomycetes to amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and flucytosine. The significant in vitro activity of posaconazole against several species appears to support its reported clinical efficacy. Decreased susceptibility to amphotericin B was noted with Cunninghamella bertholletiae. C1 Roswell Pk Canc Inst, Dept Med, Buffalo, NY USA. Dept Pathol, Fungus Testing Lab, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Mayo Clin, Phoenix, AZ USA. RP Sutton, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM suttond@uthscsa.edu NR 30 TC 131 Z9 140 U1 0 U2 1 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 JUL PY 2007 VL 51 IS 7 BP 2587 EP 2590 DI 10.1128/AAC.00452-07 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 184TS UT WOS:000247665800039 PM 17452481 ER PT J AU Nithipongvanitch, R Ittarat, W Cole, MP Tangpong, J St Clair, DK Oberley, TD AF Nithipongvanitch, Ramaneeya Ittarat, Wanida Cole, Marsha P. Tangpong, Jitbanjong St. Clair, Daret K. Oberley, Terry D. TI Mitochondrial and nuclear p53 localization in cardiomyocytes: Redox modulation by doxorubicin (adriamycin)? SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; SEQUENCE-SPECIFIC DNA; NITRIC-OXIDE; INDUCED APOPTOSIS; REACTIVE OXYGEN; SIGNALING PATHWAYS; TRANSGENIC MICE; EXCISION-REPAIR; CANCER-CELLS; EXPRESSION AB Reactive oxygen (ROS) and nitrogen species (RNS) generation have been proposed to be an important mechanism of doxorubicin (Adriamycin; ADR)-induced cardiotoxicity and cardiomyocyte apoptosis, processes that may be mediated by p53 protein. We note that ADR treatment resulted in increased levels of p53 protein in cardiomyocyte mitochondria and nuclei. Modulation of the cardiomyocyte redox state in genetically engineered mice by modulation of enzymes involved in metabolism of ROS/RNS, manganese superoxide dismutase (MnSOD), or inducible nitric oxide synthase (iNOS), or a combination of these, regulated levels of mitochondrial/nuclear p53 in cardiomyocytes after ADR administration. These observations led to the hypothesis that mitochondrial/ nuclear p53 localization and function in the cardiomyocyte response to ADR may be regulated through redox-dependent mechanism(s). C1 Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. Mahidol Univ, Fac Med Technol, Bangkok 10700, Thailand. Univ Kentucky, Dept Toxicol, Lexington, KY 40506 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Oberley, TD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. EM dstc100@pop.uky.edu FU NCI NIH HHS [CA94853] NR 38 TC 38 Z9 41 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUL PY 2007 VL 9 IS 7 BP 1001 EP 1008 DI 10.1089/ars.2007.1632 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 170EW UT WOS:000246646200019 PM 17508921 ER PT J AU Hu, XZ Rush, AJ Charney, D Wilson, AF Sorant, AJM Papanicolaou, GJ Fava, M Trivedi, MH Wisniewski, SR Laje, G Paddock, S McMahon, FJ Manji, H Lipsky, RH AF Hu, Xian-Zhang Rush, A. John Charney, Dennis Wilson, Alexander F. Sorant, Alexa J. M. Papanicolaou, George J. Fava, Maurizio Trivedi, Madhukar H. Wisniewski, Stephen R. Laje, Gonzalo Paddock, Silvia McMahon, Francis J. Manji, Husseini Lipsky, Robert H. TI Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; STAR-ASTERISK-D; DIAGNOSTIC SCREENING QUESTIONNAIRE; REUPTAKE INHIBITORS; ANTIDEPRESSANT TREATMENT; FLUOXETINE TREATMENT; QUICK INVENTORY; DRUG RESPONSE; RATING-SCALE; GENE AB Context: The HTTLPR, a functional polymorphism of the serotonin transporter gene solute carrier family 6 ( neurotransmitter transporter, serotonin), member 4 (SLC6A4), promoter, affects transcription and may be involved in antidepressant drug treatment outcome, although response rates with antidepressants can be lower in patients who experience adverse effects. Objective: To test the hypothesis that HTTLPR is associated with treatment outcome to citalopram. Design: A clinical effectiveness trial, Sequenced Treatment Alternatives to Relieve Depression, collected DNA samples from outpatients with nonpsychotic major depressive disorder who received citalopram in the first treatment step. The triallelic HTTLPR locus was genotyped in 1775 samples to discriminate between long ( L) and short (S) alleles, followed by the A > G substitution. The low-expression S and LG alleles were grouped together compared with the high-expression L-A allele. Setting: Eighteen primary care and 23 psychiatric care sites across the United States. Participants: Ages 18 to 75 years, meeting criteria for single or recurrent nonpsychotic major depression. Main Outcome Measures: Categorical response, remission, tolerance, and adverse effect burden. Results: Expression-based grouping produced a significant finding of association between the LA allele and adverse effect burden in the entire sample (P = .004 [genotype frequency]; P < .001 [allele frequency]). To control for bias from population stratification, a white American subsample was analyzed. A lesser adverse effect burden was associated with LALA genotype frequency (P = .03) or LA allele frequency ( P = .007). These findings in white patients did not hold when the L allele was undifferentiated. No association was observed between treatment outcome phenotypes and HTTLPR. Development of diarrhea and the presence of the low-expression S or L-G alleles were the strongest risk factors associated with adverse effect burden. Conclusions: The HTTLPR polymorphism is associated with citalopram adverse effects. Because the LA allele confers increased SLC6A4 transcription, increased serotonin transporter levels in brain and other tissues may lead to fewer adverse effects for antidepressant medications that target the transporter. C1 NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIMH, Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Mt Sinai Hosp, Albert Einstein Sch Med, Dept Psychiat, New York, NY 10029 USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Lipsky, RH (reprint author), NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, 5625 Fishers Ln,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM rlipsky@mail.nih.gov RI McMahon, Francis/A-7290-2009; Wilson, Alexander/C-2320-2009; Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Lipsky, Robert/0000-0001-7753-1473; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NIMH NIH HHS [N01MH90003] NR 46 TC 141 Z9 148 U1 3 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2007 VL 64 IS 7 BP 783 EP 792 DI 10.1001/archpsyc.64.7.783 PG 10 WC Psychiatry SC Psychiatry GA 185GF UT WOS:000247698700003 PM 17606812 ER PT J AU Marshall, GA Monserratt, L Harwood, D Mandelkern, M Cummings, JL Sultzer, DL AF Marshall, Gad A. Monserratt, Lorena Harwood, Dylan Mandelkern, Mark Cummings, Jeffrey L. Sultzer, David L. TI Positron emission tomography metabolic correlates of apathy in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID DEMENTIA; DEPRESSION; SPECT AB Background: Apathy is the most common neuropsychiatric manifestation in Alzheimer disease ( AD). Clinical, single-photon emission computed tomography, magnetic resonance imaging, and pathologic studies of apathy in AD have suggested an association with frontal dysfunction, most supportive of anterior cingulate abnormalities, but without a definitive localization. Objective: To examine the association between apathy and cortical metabolic rate on positron emission tomography in AD. Design: Forty-one subjects with probable AD underwent [ F-18] fluorodeoxyglucose positron emission tomography imaging and neuropsychiatric and cognitive assessments. Global subscale scores from the Scale for the Assessment of Negative Symptoms in Alzheimer Disease were used to designate the absence or presence of clinically meaningful apathy. Whole-brain voxel-based analyses were performed using statistical parametric mapping ( SPM2; Wellcome Department of Imaging Neuroscience, London, England), which yielded significance maps comparing the 2 groups. Results: Twenty-seven ( 66%) subjects did not have apathy, whereas 14 ( 34%) had apathy. Statistical parametric mapping analysis revealed significant reduced activity in the bilateral anterior cingulate region extending inferiorly to the medial orbitofrontal region ( P <.001) and the bilateral medial thalamus ( P=.04) in subjects with apathy. The results of the statistical parametric mapping analysis remained the same after individually covarying for the effects of global cognitive impairment, depressed mood, and education. Conclusions: Apathy in AD is associated with reduced metabolic activity in the bilateral anterior cingulate gyrus and medial orbitofrontal cortex and may be associated with reduced activity in the medial thalamus. These results reinforce the confluence of evidence from other investigational modalities in implicating medial frontal dysfunction and related neuronal circuits in the neurobiology of apathy in AD and other neuropsychiatric diseases. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Behav Sci, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles, Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. Vet Affairs Greater Los Angeles, Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Calif Irvine, Irvine, CA 92717 USA. RP Sultzer, DL (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. EM dsultzer@ucla.edu FU NIMH NIH HHS [MH56031] NR 25 TC 103 Z9 105 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2007 VL 64 IS 7 BP 1015 EP 1020 DI 10.1001/archneur.64.7.1015 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 188AZ UT WOS:000247892100014 PM 17620493 ER PT J AU Shen, LL Barabino, S Taylor, AW Dana, R AF Shen, Linling Barabino, Stefano Taylor, Andrew W. Dana, Reza TI Effect of the ocular microenvironment in regulating corneal dendritic cell maturation SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID AQUEOUS-HUMOR; IMMUNOSUPPRESSIVE FACTOR; IMMUNE-SYSTEM; BONE-MARROW; IDENTIFICATION; POPULATION; EXPRESSION; STROMA; BETA AB Objective: To determine whether the ocular anterior segment ( aqueous humor and cornea) actively inhibits dendritic cell ( DC) maturation. Methods: Dendritic cells were injected into syngeneic corneas or conjunctivae, and their surface major histocompatibility complex class II expression in response to the local milieu was assessed using confocal microscopy. Immature DCs were cocultured with corneal supernatant or with aqueous humor to evaluate their regulation of DC phenotypic and functional maturity. Results: In contrast to conjunctivally injected DCs, DCs injected into the cornea resisted up-regulation in expression of surface major histocompatibility complex class II. Corneal supernatant-treated and aqueous humor treated DCs retained their immaturity, as reflected by high antigen uptake but low costimulatory molecule (CD80 and CD86) expression and poor T-cell stimulation. Antitransforming growth factor beta(2) treatment of aqueous humor and of corneal supernatant led to complete and partial blockade of their inhibition of DC maturation, respectively. However, alpha-melanocyte-stimulating hormone and calcitonin gene-related peptide had no demonstrable effect on DC maturation. Conclusion: Cornea and aqueous humor, principally through transforming growth factor beta(2), promote generation of phenotypically and functionally immature DCs. Clinical Relevance: Our results indicate that relative immune quiescence in the cornea and in the anterior segment is actively maintained in part by the inhibitory effect of transforming growth factor beta(2) on resident DCs and by their suppression of T-cell-mediated immune and inflammatory responses. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cornea Serv, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, 20 Staniford St, Boston, MA 02114 USA. EM Reza.dana@schepens.harvard.edu FU NEI NIH HHS [EY01752, R01 EY010752, EY12963, R01 EY012963] NR 24 TC 26 Z9 28 U1 1 U2 1 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 JUL PY 2007 VL 125 IS 7 BP 908 EP 915 DI 10.1001/archopht.125.7.908 PG 8 WC Ophthalmology SC Ophthalmology GA 188BE UT WOS:000247892600006 PM 17620569 ER PT J AU Lessell, S AF Lessell, Simmons TI A retrospective look at prospective investigations SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Lessell, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM simmons_lessell@meei.harvard.edu NR 0 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 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2007 VL 125 IS 7 BP 965 EP 965 DI 10.1001/archopht.125.7.965 PG 1 WC Ophthalmology SC Ophthalmology GA 188BE UT WOS:000247892600016 PM 17620580 ER PT J AU Guihan, M Garber, SL Bombardier, CH Durazo-Arizu, R Goldstein, B Holmes, SA AF Guihan, Marylou Garber, Susan L. Bombardier, Charles H. Durazo-Arizu, Ramon Goldstein, Barry Holmes, Sally Ann TI Lessons learned while conducting research on prevention of pressure ulcers in veterans with spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE pressure ulcers; rehabilitation; spinal cord injuries; veterans ID METAANALYSIS; EFFICACY AB Objective: To describe the challenges of conducting a large randomized controlled trial (RCT) to assess the effectiveness of an intervention to prevent recurrent pressure ulcers among a high-risk population of subjects with spinal cord injury (SCI). Design: Prospective multisite, randomized design comparing outcomes of patients who received individualized education and structured telephone counseling follow-up with those of patients receiving customary care. This study was stopped early because of unanticipated recruitment problems. Setting: Six Veterans Affairs SCI specialty centers. Participants: Veterans (N = 150) treated for stage III or IV pelvic pressure ulcers. Interventions: Not applicable. Main Outcome Measure: Recurrence (defined as new skin breakdown in the pelvic area) and time to recurrence. The study was stopped early because of slow recruitment, so the focus of this study is lessons learned, not the main planned outcome measures. Results: Subject recruitment did not meet original expectations because almost 50% of those enrolled left the hospital with the study ulcer unhealed (having a healed ulcer was a requirement for participation). No significant differences were observed between groups on rate of or time to recurrence at the time the study was stopped. Among the 6 sites, variability in ulcer management (eg, length of stay, receipt of medical vs surgical treatment, sitting tolerance before discharge) and time to recurrence (median, 4mo) were observed. Conclusions: RCTs in real-world settings are the most robust method of assessing the effectiveness of prevention strategies. However, in complex, rapidly changing health care organizations, blinding is infeasible, it may be impractical to control for every variable that influences a study's outcome, and any assumptions that usual care is static are probably mistaken. Investigators must be prepared to use innovative approaches to maintain the integrity of the study design, including flexibility in inclusion and exclusion criteria to support accrual, obtaining a better understanding of the important aspects of usual care that may need to be standardized, continuous improvement within the intervention arm, and anticipation and minimization of risks from organizational changes. With attention to these delivery system issues and the usual design features of randomized trials, we believe real-world care settings can serve as important laboratories to test pressure ulcer prevention strategies in this population. C1 Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. Harborview Med Ctr, Seattle, WA USA. Loyola Univ, Stritch Sch Med, Dept Prevent Med & Eoidemiol, Maywood, IL 60153 USA. Vet Hlth Adm Spinal Cord Injury & Disorders Strat, Seattle, WA USA. RP Guihan, M (reprint author), Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, 151-H, Hines, IL 60141 USA. EM marylou.guihan@va.gov NR 12 TC 27 Z9 27 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2007 VL 88 IS 7 BP 858 EP 861 DI 10.1016/j.apmr.2007.03.014 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 187SQ UT WOS:000247869200006 PM 17601465 ER PT J AU McGory, ML Zingmond, DS Sekeris, E Ko, CY AF McGory, Marcia L. Zingmond, David S. Sekeris, Evan Ko, Clifford Y. TI The significance of inadvertent splenectomy during colorectal cancer resection SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY APR 30-MAY 05, 2005 CL Philadelphia, PA SP Amer Soc Colon & Rectal Surg ID SPLENIC INJURY; ADMINISTRATIVE DATA; SURGICAL-TREATMENT; SURVIVAL; INFECTION; OUTCOMES; CARE; MORBIDITY; SURGERY; QUALITY AB Objective: To examine the frequency, predictors, and outcomes following inadvertent splenectomy during colorectal cancer resection. Design: Retrospective study. Setting: Linkage of the California Cancer Registry and the California Patient Discharge Database from the Office of Statewide Health Planning and Development. Participants: Californians undergoing colorectal cancer resection from 1995 through 2001. Inadvertent splenectomy was defined as splenectomy occurring during non-T4 or non-stage IV resection. Main Outcome Measure: The rate of inadvertent splenectomy for the overall cohort and by tumor location (eg, splenic flexure, rectosigmoid). Multivariate risk-adjusted models identified predictors of inadvertent splenectomy and outcomes including length of stay and probability of death. Results: A total of 41 999 non-T4, non-stage IV colorectal cancer resections were studied. Mean age was 70.4 years; 50.4% were male; and 75.6% were non-Hispanic white. Although the overall rate of inadvertent splenectomy was less than 1%, the rate was 6% for splenic flexure tumors. A multivariate risk-adjusted model predicting inadvertent splenectomy demonstrated a statistically significant (P < .001) higher odds ratio if the tumor was located in the transverse (3.6), splenic flexure (29.2), descending (11.4), sigmoid (2.7), or rectosigmoid (2.6) regions. Using a risk-adjusted model, inadvertent splenectomy increased length of stay by 37.4% (P < .001). Perhaps most important, risk-adjusted survival analysis showed splenectomy increased the probability of death by 40% (P < .001). Conclusions: To our knowledge, this is the first large study evaluating the rates and outcomes after inadvertent splenectomy. In the population-based cohort, tumor locations from the transverse colon to the rectosigmoid significantly increased the odds of inadvertent splenectomy. In addition, inadvertent splenectomy during colorectal cancer resection increased both length of stay and probability of death. C1 [McGory, Marcia L.; Zingmond, David S.; Sekeris, Evan; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Surg Outcomes & Qualit, Los Angeles, CA 90095 USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gen Internal Med, Los Angeles, CA 90095 USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Hlth Serv, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Health Syst, Dept Surg, Los Angeles, CA USA. RP McGory, ML (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Surg Outcomes & Qualit, 10833 Le Conte Ave,72 215 Ctr Hlth Sci,Box 956904, Los Angeles, CA 90095 USA. EM mmcgory@mednet.ucla.edu FU NCI NIH HHS [5U01CA086322-06] NR 26 TC 21 Z9 22 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 2007 VL 142 IS 7 BP 668 EP 674 DI 10.1001/archsurg.142.7.668 PG 7 WC Surgery SC Surgery GA 188IN UT WOS:000247913700020 PM 17638806 ER PT J AU Finn, AV Nakazawa, G Joner, M Kolodgie, FD Mont, EK Gold, HK Virmani, R AF Finn, Aloke V. Nakazawa, Gaku Joner, Michael Kolodgie, Frank D. Mont, Erik K. Gold, Herman K. Virmani, Renu TI Vascular responses to drug eluting stents - Importance of delayed healing SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE stents; thrombosis; endothelium ID LONG-TERM OUTCOMES; BARE-METAL STENTS; MUSCLE-CELL-PROLIFERATION; TISSUE FACTOR EXPRESSION; CORONARY-ARTERY; NEOINTIMAL HYPERPLASIA; CLINICAL-IMPLICATIONS; ANTIPLATELET THERAPY; UNCOATED STENTS; SIROLIMUS AB Polymer- based sirolimus- ( Cypher) and paclitaxel- eluting ( Taxus) drug eluting stents have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention ( PCI). Although these stents reduce rates of restenosis compared with bare metal stents ( BMS), late thrombosis, a life threatening complication, has emerged as a major safety concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that both DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared with BMS. This delayed healing is the primary substrate underlying all cases of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis such as penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions represent additional barriers to healing and should be avoided if DES are to be used to minimize the risk of late thrombosis. Because the time course of complete healing with DES in man is unknown, the optimal duration of antiplatelet treatment remains to be determined. C1 CVPath Inst Inc, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. Miami Dade Cty Examiner Dept, Miami, FL USA. RP Virmani, R (reprint author), CVPath Inst Inc, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 62 TC 502 Z9 529 U1 5 U2 50 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 JUL PY 2007 VL 27 IS 7 BP 1500 EP 1510 DI 10.1161/ATVBAHA.107.144220 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 180XN UT WOS:000247401400003 PM 17510464 ER PT J AU Da Silva, N Shum, WWC Breton, S AF Da Silva, Nicolas Shum, Winnie W. C. Breton, Sylvie TI Regulation of vacuolar proton pumping ATPase-dependent luminal acidification in the epididymis SO ASIAN JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 4th Workshop on the Epididymis (Epid IV) CY DEC 04-07, 2006 CL Chatel Guyon, FRANCE DE proton pump; H*-ATPase; clear cells; bicarbonate resorption ID MALE REPRODUCTIVE-TRACT; SOLUBLE ADENYLYL-CYCLASE; ACTIN-BINDING SITE; RAT EPIDIDYMIS; H+-ATPASE; EPITHELIAL-CELLS; VAS-DEFERENS; MALE-FERTILITY; MOUSE SPERM; V-ATPASE AB Luminal acidification in the epididymis is an important process for the regulation of male fertility. Low pH and low bicarbonate concentration are among key factors that keep spermatozoa in a dormant state while they mature and are stored in this organ. Although significant bicarbonate reabsorption is achieved by principal cells in the proximal regions of the epididymis, clear and narrow cells are specialized for net proton secretion. Clear cells express very high levels of the vacuolar proton pumping ATPase (V-ATPase) in their apical membrane and are responsible for the bulk of proton secretion. In the present paper, selected aspects of V-ATPase regulation in clear cells are described and potential pathologies associated with mutations of some of the V-ATPase subunits are discussed. C1 Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,CPZN 8204, Boston, MA 02114 USA. EM sbreton@receptor.mgh.harvard.edu FU NICHD NIH HHS [HD40793, R01 HD040793]; NIDDK NIH HHS [DK38452, DK43351, DK57521, P01 DK038452] NR 52 TC 23 Z9 23 U1 1 U2 2 PU SHANGHAI INST MATERIA MEDICA PI SHANGHAI PA 555 ZU CHONG ZHI RD, ZHANG JIANG HI-TECH PARK, SHANGHAI, PUDONG 201203, PEOPLES R CHINA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD JUL 1 PY 2007 VL 9 IS 4 BP 476 EP 482 DI 10.1111/j.1745-7262.2007.00299.x PG 7 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 186AZ UT WOS:000247752800006 PM 17589784 ER PT J AU Ferreira, MAR Sham, P Daly, MJ Purcell, S AF Ferreira, Manuel A. R. Sham, Pak Daly, Mark J. Purcell, Shaun TI Ascertainment through family history of disease often decreases the power of family-based association studies SO BEHAVIOR GENETICS LA English DT Article DE association; TDT; power; study design; complex disease; family history ID QUANTITATIVE TRAITS; LINKAGE; DISEQUILIBRIUM; INHERITANCE; DESIGN; TESTS; TDT AB Selection of cases with additional affected relatives has been shown to increase the power of the case-control association design. We investigated whether this strategy can also improve the power of family-based association studies that use the transmission disequilibrium test (TDT), while accounting for the effects of residual polygenic and environmental factors on disease liability. Ascertainment of parent-offspring trios conditional on the proband having affected first-degree relatives almost always reduced the power of the TDT. For many disease models, this reduction was quite considerable. In contrast, for the same sample size, designs that analyzed more than one affected offspring per family often improved power when compared to the standard parent-offspring trio design. Together, our results suggest that (1) residual polygenic and environmental influences should be considered when estimating the power of the TDT for studies that ascertain families with multiple affected relatives; (2) if trios are selected conditional on having additional affected offspring, then it is important to genotype and include in the analysis the additional siblings; (3) the ascertainment strategy should be considered when interpreting results from TDT analyses. Our analytic approach to estimate the asymptotic power of the TDT is implemented online at http://pngu.mgh.harvard.edu/similar to purcell/gpc/. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. Univ Hong Kong, Genome Res Ctr, Hong Kong, Hong Kong, Peoples R China. Harvard Univ, Broad Inst, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. RP Ferreira, MAR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM mferreira@chgr.mgh.harvard.edu RI Sham, Pak Chung/C-4388-2009; Ferreira, Manuel/D-3609-2013 FU NEI NIH HHS [EY-12562] NR 13 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JUL PY 2007 VL 37 IS 4 BP 631 EP 636 DI 10.1007/s10519-007-9149-0 PG 6 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 181BO UT WOS:000247412000010 PM 17372818 ER PT J AU Mouche, S Mkaddem, SB Wang, W Katic, M Tseng, YH Carnesecchi, S Steger, K Foti, M Meier, CA Muzzin, P Kahn, CR Ogier-Denis, E Szanto, I AF Mouche, Sarah Mkaddem, Sanae Ben Wang, Wei Katic, Masa Tseng, Yu-Hua Carnesecchi, Stephanie Steger, Klaus Foti, Michelangelo Meier, Christoph A. Muzzin, Patrick Kahn, C. Ronald Ogier-Denis, Eric Szanto, Ildiko TI Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE reactive oxygen species; NADPH oxidase; NOX4; insulin signaling; adipocyte differentiation ID STRESS IMPAIRS INSULIN; SMOOTH-MUSCLE-CELLS; 1B IN-VIVO; NAD(P)H OXIDASE; 3T3-L1 ADIPOCYTES; OXIDATIVE STRESS; REACTIVE OXYGEN; GLUT4 TRANSLOCATION; METABOLIC SYNDROME; PLASMA-MEMBRANES AB Adipocyte differentiation is a complex process regulated among other factors by insulin and the production of reactive oxygen species (ROS). NOX4 is a ROS generating NADPH oxidase enzyme mediating insulin's action in 3T3L1 adipocytes. In the present paper we show that NOX4 is expressed at high levels both in white and])town preadipocytes and that differentiation into adipocytes results in a decrease in their NOX4 mRNA content. These in vitro results were confirmed in vivo by demonstrating that in intact adipose tissue the majority of NOX4 expressing cells are localized within the preadipocyte containing stromal/vascular fraction, rather than in the portion consisting of mature adipocytes. In line with these observations, quantification of NOX4 mRNA in fat derived from different rodent models of insulin resistance indicated that alteration in NOX4 expression reflects changes in the ratio of adipocyte/interstitial fractions. In conclusion, we reveal that decreased NOX4 mRNA content is a hallmark of adipocyte differentiation and that NOX4 expression measured in whole adipose tissue is not an unequivocal indicator of intact or impaired insulin action. (0 2007 Elsevier BN. All rights reserved. C1 Univ Geneva, Sch Med, Dept Cellular Physiol & Metab, CH-1211 Geneva 4, Switzerland. Univ Paris 07, INSERM, U773, Ctr Rech Biomed Bichat Beaujon CRB3, Paris, France. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. Univ Giessen, Dept Urol & Pediat Urol, Giessen, Germany. Univ Hosp Geneva, Endocrine Unit, Dept Internal Med, Geneva, Switzerland. Univ Geneva, Dept Rehabil & Geriatr, Geneva, Switzerland. RP Szanto, I (reprint author), Univ Geneva, Sch Med, Dept Cellular Physiol & Metab, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM ildiko.szanto@medecine.unige.ch RI Ogier-Denis, Eric/E-5030-2016 NR 54 TC 36 Z9 37 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUL PY 2007 VL 1773 IS 7 BP 1015 EP 1027 DI 10.1016/j.bbamcr.2007.03.003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 187OW UT WOS:000247858600001 PM 17553579 ER PT J AU Lai, KS Ho, NH Cheng, JD Tung, CH AF Lai, Koon Siew Ho, Nan-Hui Cheng, Jonathan D. Tung, Ching-Hsuan TI Selective fluorescence probes for dipeptidyl peptidase activity - Fibroblast activation protein and dipeptidyl peptidase IV SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SERINE-PROTEASE; STROMAL FIBROBLASTS; SUBSTRATE-SPECIFICITY; EPITHELIAL CANCERS; SMALL-MOLECULE; TUMOR-GROWTH; ALPHA; INHIBITORS; ENZYMES; PT-100 AB Development of suitable tools to assess enzyme activity directly from their complex cellular environment has a dramatic impact on understanding the functional roles of proteins as well as on the discovery of new drugs. In this study, a novel fluorescence-based chemosensor strategy for the direct readout of dipeptidase activities within intact living cells is described. Selective activity-based probes were designed to sense two important type II transmembrane serine proteases, fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). These serine proteases have been implicated in diverse cellular activities, including blood coagulation, digestion, immune responses, wound healing, tumor growth, tumor invasion, and metastasis. Here, we validated that Ac-GPGP-2SBPO and GPGP-2SBPO probes are excellent reporters of both proteolytic activities. Furthermore, the novel probes can differentiate between FAP and DPP-IV proteolytic activities in cellular assay. Potentially, this assay platform is immediately useful for novel drug discovery. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Tung, CH (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [CA006927, CA090468, CA099385, CA103991, CA114149, CA86355, K08 CA090468, P30 CA006927, P50 CA086355, R01 CA099385, R01 CA099385-04, R21 CA103991, R21 CA114149, R21 CA114149-01, R33 CA114149, R33 CA114149-02, R33 CA114149-03] NR 26 TC 14 Z9 16 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 2007 VL 18 IS 4 BP 1246 EP 1250 DI 10.1021/bc0603586 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 190UI UT WOS:000248085700029 PM 17489551 ER PT J AU Bearden, CE Thompson, PM Dalwani, M Hayashi, KM Lee, AD Nicoletti, M Trakhtenbroit, M Glahn, DC Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Soares, JC AF Bearden, Carrie E. Thompson, Paul M. Dalwani, Manish Hayashi, Kiralee M. Lee, Agatha D. Nicoletti, Mark Trakhtenbroit, Michael Glahn, David C. Brambilla, Paolo Sassi, Roberto B. Mallinger, Alan G. Frank, Ellen Kupfer, David J. Soares, Jair C. TI Greater cortical gray matter density in lithium-treated patients with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; cortical pattern matching; lithium; magnetic resonance imaging; mood disorders; neuroprotection ID VOXEL-BASED MORPHOMETRY; ANTERIOR CINGULATE CORTEX; MANIC-DEPRESSIVE ILLNESS; N-ACETYL-ASPARTATE; MOOD DISORDERS; ALZHEIMERS-DISEASE; PROTEIN BCL-2; HUMAN BRAIN; IN-VIVO; VOLUME AB Background: The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for three-dimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures. Methods: We used high-resolution magnetic resonance imaging and cortical pattern matching methods to map gray matter differences in 28 adults with bipolar disorder, 70% of whom were lithium-treated (mean age = 36.1 +/- 10.5; 13 female subject), and 28 healthy control subjects (mean age = 35.9 +/- 8.5; 11 female subjects). Detailed spatial analyses of gray matter density (GMD) were conducted by measuring local proportions of gray matter at thousands of homologous cortical locations. Results: Gray matter density was significantly greater in bipolar patients relative to control subjects in diffuse cortical regions. Greatest differences were found in bilateral cingulate and paralimbic cortices, brain regions critical for attentional, motivational, and emotional modulation. Secondary region of interest (1301) analyses indicated significantly greater GMD in the right anterior cingulate among lithium-treated bipolar patients (n = 20) relative to those not taking lithium (n = 8). Conclusions: These brain maps are consistent with previous voxel-based morphometry reports of greater GMD in portions of the anterior limbic network in bipolar patients and suggest neurotrophic effects of lithium as a possible etiology of these neuroanatomic differences. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Behav Sci, Lab Neurolmaging, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX USA. Univ Udine, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. IRCCS, Inst Sci, Udine, Italy. Univ Fed Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Bearden, CE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, 300 Bldg Med Plaza, Suite 2265, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NCRR NIH HHS [K24 RR020571, R21 RR019771, RR019771, RR020571]; NIA NIH HHS [R01 AG021431, AG021431]; NIBIB NIH HHS [EB01651, R01 EB016516]; NIMH NIH HHS [K23 MH001736, K23 MH074644, K23 MH074644-01, MH01736, MH030915, MH068662, MH068766, MH29618, P20 MH068662, P30 MH030915, P30 MH086045, R01 MH029618, R01 MH068766, R37 MH029618] NR 43 TC 155 Z9 159 U1 0 U2 6 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 JUL 1 PY 2007 VL 62 IS 1 BP 7 EP 16 DI 10.1016/j.biopsych.2006.10.027 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 184PH UT WOS:000247653500003 PM 17240360 ER PT J AU Woods, DL Martin, JL AF Woods, Diana Lynn Martin, Jennifer L. TI Cortisol and wake time in nursing home residents with behavioral symptoms of dementia SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE cortisol; wake time; behavioral symptoms; dementia; nursing home ID AGE-RELATED-CHANGES; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; CIRCADIAN-RHYTHMS; SLEEP-WAKE; STRESS; DISTURBANCES; AGITATION; BRAIN; GLUCOCORTICOIDS AB Alterations in sleep and behavioral symptoms are consistently reported among nursing home residents with dementia. Disregulation in the hypothalamic-pituitary-adrenal axis (HPA), indexed by basal cortisol levels, offers one explanation. The purpose of this study is to examine the relationship between wake time and cortisol slope in residents with behavioral symptoms. The study included 27 residents aged 71 to 84 years with dementia and behavioral symptoms. Using a within-subject longitudinal design, the researchers documented wake time and collected saliva samples for 4 consecutive days upon waking and at 30 min, 6 hr, and 12 hr after waking. Within-person cortisol slopes were categorized into zeropositive and negative slopes. The zero-positives (35%) exhibited an earlier wake time than the negatives (65%). These preliminary results suggest both a relationship between wake time and HPA diurnal profile and an association between the sleep-wake cycle and cortisol secretion among nursing home residents with dementia. C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Woods, DL (reprint author), Univ Calif Los Angeles, Sch Nursing, 700 Tiverton Ave,Box 956919, Los Angeles, CA 90095 USA. EM lwoods@sonnet.ucla.edu NR 49 TC 12 Z9 12 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD JUL PY 2007 VL 9 IS 1 BP 21 EP 29 DI 10.1177/1099800407303982 PG 9 WC Nursing SC Nursing GA 184OS UT WOS:000247652000003 PM 17601854 ER PT J AU Ballen, KK Shpall, EJ Avigan, D Yeap, BY Fisher, DC McDermott, K Dey, BR Attar, E McAfee, S Konopleva, M Antin, JH Spitzer, TR AF Ballen, Karen K. Shpall, Elizabeth J. Avigan, David Yeap, Beow Y. Fisher, David C. McDermott, Kathleen Dey, Bimalangshu R. Attar, Eyal McAfee, Steven Konopleva, Marina Antin, Joseph H. Spitzer, Thomas R. TI Phase I trial of parathyroid hormone to facilitate stem cell mobilization SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE parathyroid hormone; mobilization; stem cells ID HEMATOPOIETIC PROGENITOR CELLS; CORD BLOOD TRANSPLANTATION; COLONY-STIMULATING FACTOR; AUTOLOGOUS TRANSPLANTATION; MULTIPLE-MYELOMA; CXCR4 ANTAGONIST; CD34(+) CELLS; SELF-RENEWAL; NICHE; OSTEOBLASTS AB Autologous stem cell transplantation is a curative procedure for many patients with lymphomas, and has been shown to improve survival in patients with multiple myeloma. Approximately 20% of patients are unable to mobilize sufficient hematopoietic stem cells to proceed safely to autologous stem cell transplantation. Parathyroid hormone (PTH) affects osteoblasts and the stem cell niche, and has been shown to improve survival when given posttransplant in a mouse competitive transplant model. In this Phase I study, 20 subjects who had I or 2 unsuccessful stem cell mobilization attempts, received PTH in escalating doses of 40 jig, 60 mu g, 80 jig, and 100 mu g for 14 days. On days 10-14 of treatment, subjects received filgrastim 10 mu g/kg. The PTH was tolerated well and there was no dose-limiting toxicity. Forty-seven percent of subjects who had failed I prior mobilization attempt met the mobilization criteria of > 5 CD 34(+) cells/mu L in the peripheral blood. Forty percent of subjects who failed to reach adequate CD34(+) cell counts in 2 prior mobilization attempts met the mobilization criteria. PTH was well tolerated at doses up to 100 jig in human cancer patients. The efficacy of PTH for mobilization of hematopoietic stem cells will need to be tested in a larger Phase II study. (c) 2007 American Society for Blood and Marrow Transplantation. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Malignancies, Boston, MA 02215 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Zero Emerson Pl,Suite 118,Room 134, Boston, MA 02114 USA. EM kballen@partners.org FU NHLBI NIH HHS [U54 HL081030] NR 29 TC 63 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2007 VL 13 IS 7 BP 838 EP 843 DI 10.1016/j.bbmt.2007.03.007 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 187PV UT WOS:000247861200011 PM 17580262 ER PT J AU DeFrate, LE Li, G AF DeFrate, L. E. Li, G. TI The prediction of stress-relaxation of ligaments and tendons using the quasi-linear viscoelastic model SO BIOMECHANICS AND MODELING IN MECHANOBIOLOGY LA English DT Article ID MEDIAL COLLATERAL LIGAMENT; HUMAN PATELLAR TENDON; KNEE LIGAMENTS; STRAIN-RATE; COMPOSITIONAL PROPERTIES; MECHANICAL-PROPERTIES; CRUCIATE LIGAMENT; TISSUE; DEFORMATIONS; TENSILE AB Recent studies have questioned the ability of the quasi-linear viscoelastic (QLV) model to predict stresses and strains in response to loading conditions other than those used to fit the model. The objective of this study was to evaluate the ability of several models in the literature to predict the elastic stress response of ligament and tendon at strain levels higher than the levels used to fit the model. The constitutive models were then used to evaluate the ability of the QLV model to predict the overall stress response during stress relaxation. The models expressing stress as an exponential function of strain significantly overestimated stress when used at higher strain levels. The polynomial formulation of the Mooney-Rivlin model more accurately predicted the stress-strain behavior of ligament and tendon. The results demonstrate that the ability of the QLV model to accurately predict the stress-relaxation response is dependent in part on the accuracy of the function used to model the elastic response of the soft tissue. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Orthopaed, Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Orthopaed Surg, Durham, NC 27710 USA. EM gli1@partners.org FU NIAMS NIH HHS [R21 AR051078] NR 38 TC 18 Z9 18 U1 1 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1617-7959 J9 BIOMECH MODEL MECHAN JI Biomech. Model. Mechanobiol. PD JUL PY 2007 VL 6 IS 4 BP 245 EP 251 DI 10.1007/s107-006-0056-8 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 192NI UT WOS:000248208400003 PM 16941137 ER PT J AU Filoteo, AG Juranic, N Venyaminov, S Penheiter, A Caride, AJ Penniston, JT AF Filoteo, A. G. Juranic, N. Venyaminov, S. Penheiter, A. Caride, A. J. Penniston, J. T. TI The C-terminal tail of human plasma membrane calcium ATPase isoform 4b is intrinsically disordered (Jan 07, pg 8a, 2007) SO BIOPHYSICAL JOURNAL LA English DT Correction C1 Mayo Clin, Coll Med, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Filoteo, AG (reprint author), Mayo Clin, Coll Med, Rochester, MN 55905 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2007 VL 93 IS 2 BP 706 EP 706 PG 1 WC Biophysics SC Biophysics GA 181VW UT WOS:000247465300041 ER PT J AU Kumari, K Abraham, TE AF Kumari, Kumud Abraham, T. Emilia TI Biosorption of anionic textile dyes by nonviable biomass of fungi and yeast SO BIORESOURCE TECHNOLOGY LA English DT Article DE reactive anion dyes; textile effluent; biosorption; fungi; adsorption kinetics ID AQUEOUS-SOLUTION; DECOLORIZATION; WASTEWATERS; REMOVAL AB The nonviable biomass of Aspergillus niger, Aspergillus japonica, Rhizopus nigricans, Rhizopus arrhizus, and Saccharomyces cerevisiae were screened for biosorption of textile dyes. The selected anionic reactive dyes were C.I. Reactive Black 8, C.I. Reactive Brown 9, C.I. Reactive Green 19, C.I. Reactive Blue 38, and C.I. Reactive Blue 3. Experiments were conducted at initial dye concentration of 50, 100, 150 and 200 mg/L. The effect of initial dye concentration, dose of biosorbent loading, temperature, and pH on adsorption kinetics was studied. S. cerevisiae and R. nigricans were good biosorbents at initial dye concentration of 50 mg/L, 1 g% (w/v) biomass loading and 29 +/- 1 degrees C. R. nigricans adsorbed 90-96% dye in 15 min, at 20 degrees C and pH 6.0. The data showed an optimal fit to the Langmuir and Freundlich isotherms. The maximum uptake capacity (Q(0)) for the selected dyes was in the range 112-204 mg/g biomass. 0 2006 Elsevier Ltd. All rights reserved. C1 CSIR, Reg Res Lab, Trivandrum 695019, Kerala, India. RP Kumari, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Res Labs, Room 513,65 Landsdowne St, Cambridge, MA 02139 USA. EM Kumud_kumari@rediffmail.com; emiliatea@yahoo.com RI TVM, NIIST/E-5132-2012 OI TVM, NIIST/0000-0002-5814-466X NR 26 TC 74 Z9 75 U1 3 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-8524 J9 BIORESOURCE TECHNOL JI Bioresour. Technol. PD JUL PY 2007 VL 98 IS 9 BP 1704 EP 1710 DI 10.1016/j.biortech.2006.07.030 PG 7 WC Agricultural Engineering; Biotechnology & Applied Microbiology; Energy & Fuels SC Agriculture; Biotechnology & Applied Microbiology; Energy & Fuels GA 144UD UT WOS:000244820900003 PM 16997547 ER PT J AU Browne, ML Bell, EM Druschel, CM Gensburg, LJ Mitchell, AA Lin, AE Romitti, PA Correa, A AF Browne, Marilyn L. Bell, Erin M. Druschel, Charlotte M. Gensburg, Lenore J. Mitchell, Allen A. Lin, Angela E. Romitti, Paul A. Correa, Adolfo CA Natl Birth Defects Prevention Stud TI Maternal caffeine consumption and risk of cardiovascular malformations SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE caffeine; birth defects; epidemiology; cardiovascular malformations ID BIRTH-DEFECTS PREVENTION; CONGENITAL HEART-DEFECTS; COFFEE CONSUMPTION; PREGNANCY; EXPOSURE; HEALTH; METABOLISM; PATTERNS; NAUSEA AB Background: The physiologic effects and common use of caffeine during pregnancy call for examination of maternal caffeine consumption and risk of birth defects. Epidemiologic studies have yielded mixed results, but such studies have grouped etiologically different defects and have not evaluated effect modification. Methods: The large sample size and precise case classification of the National Birth Defects Prevention Study allowed us to examine caffeine consumption and specific cardiovascular malformation (CVM) case groups. We studied consumption of caffeinated coffee, tea, soda, and chocolate to estimate total caffeine intake and separately examined exposure to each caffeinated beverage. Smoking, alcohol, vasoactive medications, folic acid supplement use, and infant gender were evaluated for effect modification. Maternal interview reports for 4,196 CVM case infants overall and 3,957 control infants were analyzed. Results: We did not identify any significant positive associations between maternal caffeine consumption and CVMs. For tetralogy of Fallot, nonsignificant elevations in risk were observed for moderate (but not high) caffeine intake overall and among nonsmokers (ORs of 1.3 to 1.5). Risk estimates for both smoking and consuming caffeine were less than the sum of the excess risks for each exposure. We observed an inverse trend between coffee intake and risk of atrial septal defect; however, this single significant pattern of association might have been a chance finding. Conclusions: Our study found no evidence for an appreciable teratogenic effect of caffeine with regard to CVMs. C1 New York State Dept Hlth, Bur Environm & Occupat Epidemiol, Troy, NY USA. SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. MassGen Hosp Children, Genet & Teratol Unit, Boston, MA USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. RP Browne, ML (reprint author), New York State Dept Hlth, Bur Environm & Occupat Epidemiol, 547 River St,Room 200, Troy, NY USA. EM mlb10@health.state.ny.us RI Publications, NBDPS/B-7692-2013; OI Mitchell, Allen/0000-0003-0950-6799 FU PHS HHS [U50/CCU0223184] NR 36 TC 24 Z9 24 U1 2 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2007 VL 79 IS 7 BP 533 EP 543 DI 10.1002/bdra.20365 PG 11 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 190RG UT WOS:000248076000003 PM 17405163 ER PT J AU Chakraverty, R Sykes, M AF Chakraverty, Ronjon Sykes, Megan TI The role of antigen-presenting cells in triggering graft-versus-host disease and graft-versus-leukeryiia SO BLOOD LA English DT Review ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSIONS; REGULATORY T-CELLS; MINOR HISTOCOMPATIBILITY BARRIERS; STEADY-STATE CONDITIONS; BLOOD DENDRITIC CELLS; IN-VIVO; LANGERHANS CELLS; LEUKEMIA RESPONSES; CROSS-PRESENTATION AB After allogeneic blood or bone marrow transplantation, donor T cells interact with a distorted antigen-presenting cell (APC) environment in which some, but not all, host APCs are replaced by APCS from the donor. Significantly, host APCs are required for the priming of acute graft-versus-host disease (GVHD). Donor APCs play a lesser role in the induction of acute GVHD despite their predicted capacity to cross-present host antigens. In contrast, donor APCs may play a role in perpetuating the tissue injury observed in chronic GVHD. Host APCs are also required for maximal graft-versus-leukemia responses. Recent studies have suggested potential strategies by which the continued presence of host APCs can be exploited to prime strong donor immunity to tumors without the induction of GVHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. UCL, Dept Hematol, London WC1E 6BT, England. RP Chakraverty, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH East Bldg,149-5102,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [P01 CA111519, P0I CA111519, R01 CA079989, R01 R01 CA79989] NR 125 TC 80 Z9 83 U1 1 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 JUL 1 PY 2007 VL 110 IS 1 BP 9 EP 17 DI 10.1182/blood-2006-12-022038 PG 9 WC Hematology SC Hematology GA 183ZN UT WOS:000247611000008 PM 17327406 ER PT J AU Chen, Z Naveiras, O Balduini, A Mammoto, A Conti, MA Adelstein, RS Ingber, D Daley, GQ Shivdasani, RA AF Chen, Zhao Naveiras, Olaia Balduini, Alessandra Mammoto, Akiko Conti, Mary Anne Adelstein, Robert S. Ingber, Donald Daley, George Q. Shivdasani, Ramesh A. TI The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway SO BLOOD LA English DT Article ID MYOSIN HEAVY-CHAIN; PROPLATELET FORMATION; MOLECULAR-MECHANISMS; HUMAN MEGAKARYOCYTES; BLOOD-PLATELETS; LIGHT-CHAIN; STEM-CELLS; IN-VITRO; MUTATIONS; MARROW AB The gene implicated in the May-Hegglin anomaly and related macrothrombocytopenias, MYH9, encodes myosin-IIA, a protein that enables morphogenesis in diverse cell types. Defective myosin-IIA complexes are presumed to perturb megakaryocyte (MK) differentiation or generation of proplatelets. We observed that Myh9(-/-) mouse embryonic stem (ES) cells differentiate into MKs that are fully capable of proplatelet formation (PPF). In contrast, elevation of myosin-IIA activity, by exogenous expression or by mimicking constitutive phosphorylation of its regulatory myosin light chain (MLC), significantly attenuates PPF. This effect occurs only in the presence of myosin-IIA and implies that myosin-IIA influences thrombopoiesis negatively. MLC phosphorylation in MKs is regulated by Rho-associated kinase (ROCK), and consistent with our model, ROCK inhibition enhances PPF. Conversely, expression of AV14, a constitutive form of the ROCK activator Rho, blocks PPF, and this effect is rescued by simultaneous expression of a dominant inhibitory MLC form. Hematopoietic transplantation studies in mice confirm that interference with the putative Rho-ROCK-myosin-IIA pathway selectively decreases the number of circulating platelets. Our studies unveil a key regulatory pathway for platelet biogenesis and hint at Sdf-1/CXCL12 as one possible extracellular mediator. The unexpected mechanism for Myh9-associated thrombocytopenia may lead to new molecular approaches to manipulate thrombopoiesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Pavia, Dept Biochem, Fdn Ist Ricovero & Cura Carattere Sci Policlin Sa, I-27100 Pavia, Italy. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. RP Chen, Z (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way, Boston, MA 02115 USA. RI Balduini, Alessandra/K-6802-2016; OI Balduini, Alessandra/0000-0003-3145-1245; Adelstein, Robert/0000-0002-8683-2144 FU NCI NIH HHS [CA55883]; NHLBI NIH HHS [R01 HL063143, HL63143, R56 HL063143]; Telethon [GGP06177] NR 51 TC 90 Z9 91 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2007 VL 110 IS 1 BP 171 EP 179 DI 10.1182/blood-2007-02-071589 PG 9 WC Hematology SC Hematology GA 183ZN UT WOS:000247611000028 PM 17392504 ER PT J AU Dey, BR Shaffer, J Yee, AJ McAfee, S Caron, M Power, K Ting, DT Colby, C Preffer, F Ballen, K Attar, E Saidman, S Tarbell, N Sachs, D Sykes, M Spitzer, TR AF Dey, B. R. Shaffer, J. Yee, A. J. McAfee, S. Caron, M. Power, K. Ting, D. T. Colby, C. Preffer, F. Ballen, K. Attar, E. Saidman, S. Tarbell, N. Sachs, D. Sykes, M. Spitzer, T. R. TI Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen SO BONE MARROW TRANSPLANTATION LA English DT Article DE PBSC; bone marrow; nonmyeloablative; chimerism ID VERSUS-HOST-DISEASE; COLONY-STIMULATING FACTOR; ALLOGENEIC TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; PROGENITOR CELLS; DENDRITIC CELLS; T-LYMPHOCYTES; IMMUNE RECONSTITUTION; CYTOKINE PRODUCTION; RANDOMIZED-TRIAL AB This is the first study to examine the outcomes in 54 patients with hematologic malignancies who received an HLA-matched related donor bone marrow (BM, n = 42) or GCSF-mobilized peripheral blood stem cells (PBSC, n 12) following identical nonmyeloablative conditioning with the intention of induction of mixed chimerism (MC) followed by prophylactic donor leukocyte infusion (pDLI) to convert MC to full donor chimerism (FDC) and capture a graft-versus-tumor effect without clinical graft-versus-host disease (GVHD). Neutrophil and platelet recovery were faster and transfusion requirement was less in PBSC recipients (P < 0.05). A total of 48% of BMT recipients achieved FDC with a median conversion time of 84 days, including 13 following pDLI. In contrast, 83% (P = 0.04) in the PBSC group had spontaneous FDC at a median of 14 days, precluding the administration of pDLI. There was no significant difference in the incidences of acute or chronic GVHD, though the rates of chronic GVHD were considerably higher in PBSC group than in the BM group (6/7, 86% vs 10/24, 42%). CD4 and CD8 T-cell recovery was faster in PBSC recipients. In PBSC recipients, a higher number of CD34(+) cells was associated with increased rates of severe, grade III - IV acute GVHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Colby, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. EM ccolbysams@partners.org OI Ting, David/0000-0002-3261-2322 NR 46 TC 20 Z9 21 U1 0 U2 3 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 JUL PY 2007 VL 40 IS 1 BP 19 EP 27 DI 10.1038/sj.bmt.1705688 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 180NW UT WOS:000247373300003 PM 17468773 ER PT J AU Ringman, JM O'Neill, J Geschwind, D Medina, L Apostolova, LG Rodriguez, Y Schaffen, B Varpetian, A Tseng, B Ortiz, F Fitten, J Cummings, JL Bartzokis, G AF Ringman, John M. O'Neill, Joseph Geschwind, Daniel Medina, Luis Apostolova, Liana G. Rodriguez, Yaneth Schaffen, Barbara Varpetian, Arousiak Tseng, Benjamin Ortiz, Freddy Fitten, Jaime Cummings, Jeffrey L. Bartzokis, George TI Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations SO BRAIN LA English DT Article DE familial Alzheimer's disease; presymptomatic; diffusion tensor imaging; fractional anisotropy; Presenilin-I; amyloid precursor protein; white matter; fornix; biomarker ID MILD COGNITIVE IMPAIRMENT; MATTER STRUCTURAL INTEGRITY; SPASTIC PARAPARESIS; MYELIN BREAKDOWN; BRAIN; AGE; DEMENTIA; AD; ROBUST; MODEL AB Measures are needed that identify persons that will develop Alzheimer's disease in order to target them for preventative interventions. There is evidence from animal, pathological and imaging studies that disruption of white matter occurs in the course of Alzheimer's disease and may be an early event. Prior studies have suggested that late-myelinating regions or white matter connecting limbic structures are particularly susceptible to degradation. Persons destined to develop the disease by virtue of fully penetrant genetic alterations (familial Alzheimer's disease or FAD) provide a model in which early and even presymptomatic changes of the disease may be identified. In this study we performed diffusion tensor imaging (DTI) on 2 demented and 21 subjects at-risk for inheriting an FAD mutation. We compared global and localized fractional anisotropy (FA) measures in white matter between FAD mutation carriers and non-carriers in the preclinical (clinical dementia rating <1, n = 20) and presymptomatic (clinical dementia rating = 0, n = 15) stages of the disease. There were no significant differences between mutation carriers and non-carriers with regard to absolute age, age relative to the typical age of disease diagnosis in their family, gender or Mini-Mental Status Examination Score. Among preclinical FAD mutation carriers (n = 12), mean whole brain white-matter FA (P = 0.045), FA of the columns of the fornix (P = 0.012), area of the perforant pathways bilaterally (right side: P = 0.028, left side: P = 0.027) and left orbitofrontal lobe (P = 0.024) were decreased relative to that of non-carriers (n = 8). We also found that FA in the columns of the fornix (P = 0.008) and left orbitofrontal lobe white matter (P = 0.045) were decreased in the eight presymptomatic mutation carriers compared to seven non-carriers. Logistic regression demonstrated that FA of the columns of the fornix was a better predictor of mutation status than was cross-sectional area of the fornix, global mean white-matter FA and left frontal lobe white-matter FA. In a linear regression analysis, white-matter volume (P = 0.002), hippocampal volume (P = 0.023) and mutation status (P = 0.032) significantly predicted fornix FA. We conclude that FA is decreased in the white matter in preclinical and even presymptomatic FAD mutation carriers, particularly in the late-myelinating tracts connecting limbic structures. Decreased FA in of the columns of the fornix is particularly robust in early FAD and may provide a biomarker for early disease in sporadic Alzheimer's disease. C1 Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Natl Inst Neurol & Neurosurg, Expt Psychol Lab, Mexico City, DF, Mexico. Univ So Calif, Keck Sch Med, Rancho Los Amigos Natl Rehabilitat Ctr, Dept Neurol, Downey, CA USA. Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Neuropsychiat Res Memory Clin, Sylmar, CA USA. VA Greater Los Angeles Hlthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Ringman, JM (reprint author), Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Dept Neurol, 10911 Weyburn Ave,Suite 200, Los Angeles, CA 90095 USA. EM jringman@mednet.ucla.edu RI Bartzokis, George/K-2409-2013 FU NCRR NIH HHS [M01-RR00865]; NIA NIH HHS [AG-16570, K08 AG-22228] NR 38 TC 130 Z9 135 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2007 VL 130 BP 1767 EP 1776 DI 10.1093/brain/awm102 PN 7 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 191SC UT WOS:000248151300007 PM 17522104 ER PT J AU Goss, PE Qi, SL Hu, HQ Cheung, AM AF Goss, Paul E. Qi, Shangle Hu, Haiqing Cheung, Angela M. TI The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE atamestane; toremifene; letrozole; bone; lipid; uterine histology; ovariectomized rat model ID AROMATASE INHIBITOR EXEMESTANE; STAGE BREAST-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; TAMOXIFEN; RECEPTOR; HISTOMORPHOMETRY; LIPOPROTEINS; CHOLESTEROL; ANASTROZOLE AB We compared the effects of atamestane (ATA) and toremifene (TOR) alone and in combination, with letrozole (LET) on bone, serum lipids and the uterus in ovariectomized (OVX) rats after 16 weeks of treatment. Compared to OVX controls lumbar vertebral and femoral BMD as well as mechanical strength and trabecular bone volume were significantly greater in animals given ATA, TOR or ATA + TOR. The effects of ATA were not reversed by the androgen receptor blocker, flutamide (FLT). Serum cholesterol, low-density lipoprotein cholesterol and triglycerides were reduced by TOR and ATA + TOR whereas they remained unchanged in animals receiving ATA, ATA + FLT, and LET. The uterine epithelium in OVX animals was equally stimulated by TOR and ATA + TOR and unaffected by ATA or LET. Intact animals had significant atrophy of the uterine epithelium when receiving ATA. In summary, TOR alone or in combination with ATA had a predictable stimulatory effect on bone and the uterine epithelium while reducing key parameters of lipid metabolism. In contrast, ATA but not LET had an unexpected stimulatory effect on the OVX rat's bone and this was not reversed by the anti-androgen FLT leaving this finding unexplained for now. ATA is distinct from LET on end-organ function and this favorable profile makes clinical testing of this steroidal aromatase inhibitor of interest in the clinical setting. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Breast Canc Dis Program,Dana Farber Harv, Boston, MA 02114 USA. Univ Toronto, Dept Med, Osteoporosis Program, Univ Hlth Network, Toronto, ON M5G 2C4, Canada. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 2C4, Canada. RP Goss, PE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Breast Canc Dis Program,Dana Farber Harv, 55 Fruit St,Cox Bldg,Suite 640, Boston, MA 02114 USA. FU Canadian Institutes of Health Research [44917] NR 45 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2007 VL 103 IS 3 BP 293 EP 302 DI 10.1007/s10549-006-9381-y PG 10 WC Oncology SC Oncology GA 178YP UT WOS:000247256600004 PM 17063268 ER PT J AU Silverman, DHS Dy, CJ Castellon, SA Lai, J Pio, BS Abraham, L Waddell, K Petersen, L Phelps, ME Ganz, PA AF Silverman, Daniel H. S. Dy, Christine J. Castellon, Steven A. Lai, Jasmine Pio, Betty S. Abraham, Laura Waddell, Kari Petersen, Laura Phelps, Michael E. Ganz, Patricia A. TI Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE positron emission tomography; brain; breast cancer; tamoxifen; adjuvant chemotherapy; FDG; cerebral blood flow ID ESTROGEN REPLACEMENT THERAPY; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; STANDARD-DOSE CHEMOTHERAPY; HEALTH INITIATIVE MEMORY; CEREBRAL-BLOOD-FLOW; COGNITIVE FUNCTION; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; LONG-TERM AB Purpose To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer. Patients and methods Subjects treated for breast cancer with adjuvant chemotherapy remotely (5-10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis. Results During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects. Conclusion Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5-10 years after completion of chemotherapy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Silverman, DHS (reprint author), Univ Calif Los Angeles, Med Ctr, Ahmanson Biol Imaging Div, CHS AR-144,MC694215, Los Angeles, CA 90095 USA. EM dsilver@ucla.edu NR 68 TC 192 Z9 199 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2007 VL 103 IS 3 BP 303 EP 311 DI 10.1007/s10549-006-9380-z PG 9 WC Oncology SC Oncology GA 178YP UT WOS:000247256600005 PM 17009108 ER PT J AU Watson, A Bergman, H Seo, SJ Tsai, K Kvedar, J AF Watson, A. Bergman, H. Seo, S-J. Tsai, K. Kvedar, J. TI Evaluation of digital images to assess clinical progress in patients with acne SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract CT 87th Annual Meeting of the British-Association-of-Dermatologists CY JUL 10-13, 2007 CL Birmingham, ENGLAND SP British Assco Dermatologists C1 Harvard Univ, Sch Med, Ctr Connected Hlth, Dept Dermatol,Massachusetts Gen Hosp, Boston, MA 02115 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 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUL PY 2007 VL 157 SU 1 BP 24 EP 24 PG 1 WC Dermatology SC Dermatology GA 192FC UT WOS:000248185200049 ER PT J AU Anderson, KC Hannah, AL Pazdur, R Farrell, AT AF Anderson, Kenneth C. Hannah, Alison L. Pazdur, Richard Farrell, Ann T. TI A strategic framework for novel drug development in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Editorial Material DE multiple myeloma; accelerated approval; surrogate biomarker studies ID CLINICAL-TRIAL; PHASE-II; BORTEZOMIB; DEXAMETHASONE; ONCOLOGY; CANCER C1 Harvard Univ, Sch Med, Dept Med, Div Hematol Neoplasia,Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dept Med, Div Hematol Neoplasia,Dana Farber Canc Inst, 44 Binney St,Mayer 557, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 15 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2007 VL 138 IS 2 BP 153 EP 159 DI 10.1111/j.1365-2141.2007.06641.x PG 7 WC Hematology SC Hematology GA 181ZV UT WOS:000247475800003 PM 17593022 ER PT J AU Feng, H Langenau, DM Madge, JA Quinkertz, A Gutierrez, A Neuberg, DS Kanki, JP Look, AT AF Feng, Hui Langenau, David M. Madge, Jennifer A. Quinkertz, Andre Gutierrez, Alejandro Neuberg, Donna S. Kanki, John P. Look, A. Thomas TI Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE T-cell acute lymphoblastic leukaemia; Myc; Cre; heat shock; tumour onset ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYC; GENE-EXPRESSION; NOTCH1; MODEL; PATHWAYS; DISEASE; CANCER AB The zebrafish is an ideal vertebrate model system to investigate the complex genetic basis of cancer because it has the capacity for in vivo tumour-cell imaging and forward genetic screens, and the molecular mechanisms regulating malignancy are remarkably conserved when compared with human. Our laboratory has previously generated transgenic zebrafish models that overexpress the mouse c-Myc gene fused to enhanced green fluorescent protein (EGFP) and develop T-cell acute lymphoblastic leukaemia (T-ALL) that recapitulates the human disease both molecularly and pathologically. Our previous models have been limited by disease onset prior to sexual maturity and by the low disease penetrance when conditional transgenic embryos are injected with Cre RNA. Here, we report a novel system in which compound transgenic fish expressed both Cre controlled by the heat-shock promoter and a rag2-promoter-regulated lox-dsRED2-lox-EGFP-mMyc cassette rag2-LDL-EMyc in developing T cells. After heat-shock treatment at 3 d postfertilisation (dpf) for 45 min at 37 degrees C, 81% of compound transgenic fish developed T-lymphoblastic lymphoma (T-LBL, mean latency 120 +/- 43 (standard deviation) days of life), which rapidly progressed to TALL. Heat-shock-regulated transgenic technology in zebrafish provides the missing link necessary to exploit the powerful genetic capacity of this organism to probe the multi-step molecular pathogenesis of leukaemia. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Univ Cologne, Inst Dev Biol, Cologne, Germany. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Gutierrez, Alejandro/0000-0002-0249-9007; Feng, Hui/0000-0003-1318-821X FU NCI NIH HHS [CA-119066, CA-68484]; NHLBI NIH HHS [T32-HL007574] NR 23 TC 70 Z9 72 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2007 VL 138 IS 2 BP 169 EP 175 DI 10.1111/j.1365-2141.2007.06625.x PG 7 WC Hematology SC Hematology GA 181ZV UT WOS:000247475800005 PM 17593023 ER PT J AU Kim, SYH Appelbaum, PS Swan, J Stroup, TS McEvoy, JP Goff, DC Jeste, DV Lamberti, JS Leibovici, A Caine, ED AF Kim, Scott Y. H. Appelbaum, Paul S. Swan, Jeffrey Stroup, T. Scott McEvoy, Joseph P. Goff, Donald C. Jeste, Dilip V. Lamberti, J. Steven Leibovici, Adrian Caine, Eric D. TI Determining when impairment constitutes incapacity for informed consent in schizophrenia research SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID MACARTHUR TREATMENT COMPETENCE; DECISION-MAKING CAPACITY; PSYCHIATRIC-INPATIENTS; ALZHEIMERS-DISEASE; PARTICIPATION; STANDARDS; TRIALS; DESIGN AB Background Although people with schizophrenia display impaired abilities for consent, it is not known how much impairment constitutes incapacity. Aims To assess a method for determining the categorical capacity status of potential participants in schizophrenia research. Method Expert-judgement validation of capacity thresholds on the sub-scales of the MacArthur Competence Assessment Tool - Clinical Research (MacCAT-CR) was evaluated using receiver operating characteristic (ROC) analysis in 91 people with severe mental illness and 40 controls. Results The ROC areas under the curve for the understanding, appreciation and reasoning sub-scales of the MacCAT-CR were 0.94 (95% CI 0.88-0.99),0.85 (95% CI 0.76-0.94) and 0.80 (95% CI 0.70-0.90). These findings yielded negative and positive predictive values of incapacity that can guide the practice of investigators and research ethics committees. Conclusions By performing such validation studies for a few categories of research with varying risks and benefits, it might be possible to create evidence-based capacity determination guidelines for most schizophrenia research. C1 Univ Michigan, Dept Psychiat, Bioeth Program, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Behav & Decis Sci Med, Ann Arbor, MI 48109 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. VA San Diego Healthcare Syst, San Diego, CA USA. RP Kim, SYH (reprint author), 300 N Ingalls, Ann Arbor, MI 48109 USA. EM scottkim@umich.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH90001, K23 MH64172] NR 31 TC 27 Z9 27 U1 1 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUL PY 2007 VL 191 BP 38 EP 43 DI 10.1192/bjp.bp.106.033324 PG 6 WC Psychiatry SC Psychiatry GA 187QR UT WOS:000247863600007 PM 17602123 ER PT J AU D'Amico, AV Chen, MH Catalona, WJ Sun, L Roehl, KA Moul, JW AF D'Amico, Anthony V. Chen, Ming-Hui Catalona, William J. Sun, Leon Roehl, Kimberly A. Moul, Judd W. TI Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors SO CANCER LA English DT Article DE prostate cancer; mortality; radical prostatectomy; radiation therapy ID COMPETING RISK; ANTIGEN LEVEL; PSA VELOCITY; MITOXANTRONE; PREDNISONE; DOCETAXEL; DEATH AB BACKGROUND. Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >= 1 high-risk factors. METHODS. The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity > 2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of > 7, a PSA level of >= 10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. RESULTS. Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P <.001) or RT (P <=.001). The solitary presence of a PSA velocity > 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P =.05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P -.02]) when compared with men with any other single high-risk factor. CONCLUSIONS. Men with a PSA velocity > 2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. Duke Univ, Dept Urol, Raleigh, NC USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@partners.org NR 18 TC 35 Z9 35 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 JUL 1 PY 2007 VL 110 IS 1 BP 56 EP 61 DI 10.1002/cncr.22737 PG 6 WC Oncology SC Oncology GA 180RU UT WOS:000247384200007 PM 17530618 ER PT J AU Settleman, J Kurie, JM AF Settleman, Jeffrey Kurie, Jonathan M. TI Drugging the bad "AKT-TOR" to overcome TKI-resistant lung cancer SO CANCER CELL LA English DT Editorial Material ID ACQUIRED-RESISTANCE; EGFR MUTATION; GEFITINIB; INHIBITORS; RECEPTOR AB EGFR kinase inhibitors constitute an important class of lung cancer treatments. While they produce dramatic responses in a subset of patients- primarily those with activating EGFR mutations- remissions are typically limited to several months due to acquired drug resistance, frequently associated with the secondary T790M mutation in EGFR. In this issue of Cancer Cell, Li et al. report that an irreversible EGFR kinase inhibitor, HKI-272, had limited activity in a mouse lung cancer model driven by an EGFR mutant harboring T790M and an activating mutation. However, combining HKI-272 with rapamycin promoted rapid tumor regression, suggesting a therapeutic strategy to overcome drug resistance. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kurie, JM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. EM jkurie@mdanderson.org NR 9 TC 10 Z9 10 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2007 VL 12 IS 1 BP 6 EP 8 DI 10.1016/j.ccr.2007.06.010 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 189YU UT WOS:000248025700003 PM 17613432 ER PT J AU Li, DN Shimamura, T Ji, HB Chen, L Haringsma, HJ McNamara, K Liang, MC Perera, SA Zaghlul, S Borgman, CL Kubo, S Takahashi, M Sun, YP Chirieac, LR Padera, RF Lindeman, NI Janne, PA Thomas, RK Meyerson, ML Eck, MJ Engelman, JA Shapiro, GI Wong, KK AF Li, Danan Shimamura, Takeshi Ji, Hongbin Chen, Liang Haringsma, Henry J. McNamara, Kate Liang, Mei-Chih Perera, Samanthi A. Zaghlul, Sara Borgman, Christa L. Kubo, Shigeto Takahashi, Masaya Sun, Yanping Chirieac, Lucian R. Padera, Robert F. Lindeman, Neal I. Janne, Pasi A. Thomas, Roman K. Meyerson, Matthew L. Eck, Michael J. Engelman, Jeffrey A. Shapiro, Geoffrey I. Wong, Kwok-Kin TI Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy SO CANCER CELL LA English DT Article ID GROWTH-FACTOR-RECEPTOR; SMALL-CELL LUNG; TYROSINE KINASE INHIBITOR; RESISTANCE MUTATION; ACQUIRED-RESISTANCE; DOMAIN MUTATIONS; CANCER; GEFITINIB; MTOR; ADENOCARCINOMAS AB The EGFR T790M mutation has been identified in tumors from lung cancer patients that eventually develop resistance to erlotinib. In this study, we generated a mouse model with doxycycline-inducible expression of a mutant EGFR containing both L858R, an erlotinib-sensitizing mutation, and the T790M resistance mutation (EGFR TL). Expression of EGFR TL led to development of peripheral adenocarcinomas with bronchioloalveolar features in alveoli as well as papillary adenocarcinomas in bronchioles. Treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI), HKI-272, shrunk only peripheral tumors but not bronchial tumors. However, the combination of HKI-272 and rapamycin resulted in significant regression of both types of lung tumors. This combination therapy may potentially benefit lung cancer patients with the EGFR T790M mutation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany. Univ Cologne, Fac Med, D-50931 Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. Broat Inst Harvard, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu; kwong1@partners.org RI Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [P20 CA90578, R01 CA122794, R01 CA90687]; NIA NIH HHS [K08 AG024004, R01 AG2400401] NR 33 TC 138 Z9 147 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2007 VL 12 IS 1 BP 81 EP 93 DI 10.1016/j.ccr.2007.06.005 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 189YU UT WOS:000248025700009 PM 17613438 ER PT J AU Lockhart, AC Bukowski, R Rothenberg, ML Wang, KK Cooper, W Grover, J Appleman, L Mayer, PR Shapiro, M Zhu, AX AF Lockhart, A. C. Bukowski, R. Rothenberg, M. L. Wang, K. K. Cooper, W. Grover, J. Appleman, L. Mayer, P. R. Shapiro, M. Zhu, A. X. TI Phase I trial of oral MAC-321 in subjects with advanced malignant solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE phase I; clinical trial; MAC-321; paclitaxel; docetaxel ID EPOTHILONE-B ANALOG; CELL LUNG-CANCER; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; TAXANE; EXPRESSION; MECHANISMS; PACLITAXEL; APOPTOSIS; GENES AB Purpose MAC-321 is a novel taxane that has demonstrated exceptional activity in human xenograft models when administered intravenously and orally. Preclinical studies of MAC-321 have shown antitumor activity in MDR-expressing and paclitaxel-resistant tumors. This phase I dose escalation study was performed to determine the safety, tolerability, and pharmacokinetic profile of orally administered MAC-321 given once every 21 days. Preliminary antitumor activity of MAC-321 was also examined. Methods Key eligibility criteria included adult subjects with refractory solid tumors or solid tumors for which conventional therapy was unsuitable or did not exist, good performance status (ECOG (2), and adequate hematologic, hepatic, and renal functions. Plasma pharmacokinetic (PK) sampling was performed during the first cycle of therapy. Results Five dose levels of MAC-321 ranging from 25 to 75 mg/m(2) stop were evaluated in 18 subjects (four women and 14 men). MAC-321 was well tolerated at the first three dose levels (25, 37, 50 mg/m(2)). Two subjects developed dose-limiting toxicities (DLTs) at 75 mg/m(2); one subject with grade 3 and one subject with grade 4 neutropenia with fever. Three subjects treated at an intermediate dose level of 60 mg/m(2) had no DLTs. However, the study was terminated prior to completion of the maximal tolerated dose cohort after subjects treated with intravenous MAC-321 in a concurrent study experienced life-threatening toxicities. Other common toxicities included grades 1-2 fatigue and grades 1-2 diarrhea. There was substantial interpatient variability in the PK parameters. MAC-321 was rapidly absorbed with a mean C-max value of less than 1 h. Mean C-max and AUC values generally increased in a dose-related manner. The median terminal phase elimination half-life was 45 h (range 20-228 h). Disease stabilization was seen in four subjects with the following tumors: mesothelioma (14 cycles), chondrosarcoma (12 cycles), small cell carcinoma (10 cycles), and prostate carcinoma (6 cycles). Conclusions MAC-321 can be safely administered orally once every 21 days up to a dose of 60 mg/m(2). The major DLT was neutropenic fever. Four subjects had disease stabilization. C1 Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN 37232 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Wyeth Res, Cambridge, MA USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA. RP Lockhart, AC (reprint author), Vanderbilt Univ, Med Ctr, Div Hematol Oncol, 777 Preston Res Bldg, Nashville, TN 37232 USA. EM craig.lockhart@vanderbilt.edu OI Appleman, Leonard/0000-0003-4951-7388 NR 22 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2007 VL 60 IS 2 BP 203 EP 209 DI 10.1007/s00280-006-0362-y PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 166MZ UT WOS:000246384300006 PM 17091249 ER PT J AU Florin, TA Fryer, GE Miyoshi, T Weitzman, M Mertens, AC Hudson, MM Sklar, CA Emmons, K Hinkle, A Whitton, J Stovall, M Robison, LL Oeffinger, KC AF Florin, Todd A. Fryer, G. Edgar Miyoshi, Thomas Weitzman, Michael Mertens, Ann C. Hudson, Melissa M. Sklar, Charles A. Emmons, Karen Hinkle, Andrea Whitton, John Stovall, Marilyn Robison, Leslie L. Oeffinger, Kevin C. TI Physical inactivity in adult survivors of childhood acute lymphoblastic leukemia: A report from the childhood cancer survivor study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-HORMONE TREATMENT; LONG-TERM SURVIVORS; BODY-MASS INDEX; ENERGY-EXPENDITURE; DEFICIENT ADULTS; METABOLIC SYNDROME; CONTROLLED-TRIALS; SKELETAL-MUSCLE; YOUNG-ADULTS; EXERCISE AB Purpose: To determine if adult survivors of childhood acute lymphoblastic leukemia (ALL) are less active (and more inactive) than the general population and to identify modifying factors. Patients and Methods: Physical activity was assessed by self-report in 2,648 adult survivors of the Childhood Cancer Survivor Study. Participants in the Behavioral Risk Factor Surveillance System (BRFSS) survey administered through the Centers for Disease Control and Prevention (CDC) were used as a comparison group. Results: Survivors had a mean age of 28.7 years (range, 18.0-44.0 years) and were a mean of 23.1 years from their cancer diagnosis (range, 16.0-33.8 years). In multivariate models, ALL survivors were more likely to not meet CDC recommendations for physical activity [odds ratio (OR), 1.44; 95% confidence interval (95% CI), 1.32-1.571 and more likely to be inactive (OR, 1.74; 95% CI, 1.56-1.94) in comparison with the BRFSS general population. Survivors treated with > 20-Gy cranial radiotherapy were at particular risk. Compared with BRFSS participants and adjusted for age, race, and ethnicity, survivors were more likely to not meet CDC recommendations (females: OR, 2.07, 95% CI, 1.67-2.56; males: OR, 1.43, 95% CI, 1.16-1.76) and more likely to be inactive (females: OR, 1.86; 95% CI, 1.50-2.31; males: OR, 1.84; 95% CI, 1.45-2.32). Conclusions: Long-term survivors of childhood ALL are less likely to meet physical activity recommendations and more likely to report no leisure-time physical activity in the past month. This level of inactivity likely further increases their risk of cardiovascular disease, osteoporosis, and all-cause mortality. C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. NYU, Sch Med, New York, NY USA. Univ Minnesota, Minneapolis, MN 55417 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. EM oeffingk@mskcc.org FU NCI NIH HHS [R01 CA100474, R01 CA100474-04, R01-CA-100474, U24 CA055727, U24-CA-55727] NR 48 TC 92 Z9 93 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2007 VL 16 IS 7 BP 1356 EP 1363 DI 10.1158/1055-9965.EPI-07-0048 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 192BD UT WOS:000248174800005 PM 17627001 ER PT J AU Couch, FJ Sinilnikova, O Vierkant, RA Pankratz, VS Fredericksen, ZS Stoppa-Lyonnet, D Coupier, I Hughes, D Hardouin, A Berthet, P Peock, S Cook, M Baynes, C Hodgson, S Morrison, PJ Porteous, ME Jakubowska, A Lubinski, J Gronwald, J Spurdle, AB KConFab Schmutzler, R Versmold, B Engel, C Meindl, A Sutter, C Horst, J Schaefer, D Offit, K Kirchhoff, T Andrulis, IL Ilyushik, E Glendon, G Devilee, P Vreeswijk, MPG Vasen, HFA Borg, A Backenhorn, K Struewing, JP Greene, MH Neuhausen, SL Rebbeck, TR Nathanson, K Domchek, S Wagner, T Garber, JE Szabo, C Zikan, M Foretova, L Olson, JE Sellers, TA Lindor, N Ll, HN Tommiska, J Aittomaki, K Hamann, U Rashid, MU Torres, D Simard, J Durocher, F Guenard, F Lynch, HT Isaacs, C Weitzel, J Olopade, OI Narod, S Daly, MB Godwin, AK Tomlinson, G Easton, DF Chenevix-Trench, G Antoniou, AC AF Couch, Fergus J. Sinilnikova, Olga Vierkant, Robert A. Pankratz, V. Shane Fredericksen, Zachary S. Stoppa-Lyonnet, Dominique Coupier, Isabelle Hughes, David Hardouin, Agnes Berthet, Pascaline Peock, Susan Cook, Margaret Baynes, Caroline Hodgson, Shirley Morrison, Patrick J. Porteous, Mary E. Jakubowska, Anna Lubinski, Jan Gronwald, Jacek Spurdle, Amanda B. kConFab Schmutzler, Rita Versmold, Beatrix Engel, Christoph Meindl, Alfons Sutter, Christian Horst, Jurgen Schaefer, Dieter Offit, Kenneth Kirchhoff, Tomas Andrulis, Irene L. Ilyushik, Eduard Glendon, Gordon Devilee, Peter Vreeswijk, Maaike P. G. Vasen, Hans F. A. Borg, Ake Backenhorn, Katja Struewing, Jeffery P. Greene, Mark H. Neuhausen, Susan L. Rebbeck, Timothy R. Nathanson, Katherine Domchek, Susan Wagner, Theresa Garber, Judy E. Szabo, Csilla Zikan, Michal Foretova, Lenka Olson, Janet E. Sellers, Thomas A. Lindor, Noralane Ll, Heli Nevanlinna Tommiska, Johanna Aittomaki, Kristiina Hamann, Ute Rashid, Muhammad U. Torres, Diana Simard, Jacques Durocher, Francine Guenard, Frederic Lynch, Henry T. Isaacs, Claudine Weitzel, Jeffrey Olopade, Olufunmilayo I. Narod, Steven Daly, Mary B. Godwin, Andrew K. Tomlinson, Gail Easton, Douglas F. Chenevix-Trench, Georgia Antoniou, Antonis C. CA CIM Brca1 2 TI AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNKNOWN CLINICAL-SIGNIFICANCE; DNA-SEQUENCE VARIANTS; AURORA-A; SUSCEPTIBILITY GENE; MOUSE AB The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. C1 Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Med Genet, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. Hospices Civils, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. IARC, Lyon, France. Inst Curie, Serv Genet Oncol, Inst Natl Sante & Rech Med, U509, Paris, France. Ctr Francois Baclesse, Caen, France. Univ Cambridge, Canc Res UK, Genet Epidemiol Unit, Dept Publ Hlth, Cambridge CB2 1TN, England. Univ Cambridge, Human Canc Genet Grp, Dept Oncol, Cambridge CB2 1TN, England. St George Hosp, SW Thames Reg Genet Serv, London, England. Belfast City Hosp, Canc Genet Serv, No Ireland Reg Genet Ctr, Belfast BT9 7AD, Antrim, North Ireland. Western Gen Hosp, SE Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Kathleen Cuningham Fdn Consortium Res Familial Br, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Cologne, Div Mol Gynecooncol, D-5000 Cologne 41, Germany. Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-7010 Leipzig, Germany. Tech Univ Munich, Dept Gynaecol & Obstet, D-8000 Munich, Germany. Univ Heidelberg, Inst Human Genet, D-6900 Heidelberg, Germany. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Univ Munster, Munster, Germany. Univ Frankfurt, Inst Human Genet, D-6000 Frankfurt, Germany. Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. Ctr Res Womens Hlth, Toronto, ON, Canada. Leiden Univ, Ctr Med, Dept Human Genet, NL-2300 RA Leiden, Netherlands. Fdn Detect Hereditary Tumors, Leiden, Netherlands. Lund Univ Hosp, Dept Oncol, Lund, Sweden. NCI, Clin Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Med Univ Vienna, Div Senol, Vienna, Austria. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Charles Univ Prague, Fac Med 1, Dept Biochem & Expt Oncol, CR-11636 Prague, Czech Republic. Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL USA. Univ Helsinki, Dept Obstet & Gynecol, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Clin Genet, FIN-00014 Helsinki, Finland. Univ Laval, Quebec City, PQ G1K 7P4, Canada. Univ Quebec, Cent Hosp, Canc Genom Lab, Quebec City, PQ, Canada. Univ Quebec, Cent Hosp, Oncol & Mol Endocrinol Res Ctr, Quebec City, PQ, Canada. Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. City Hope Canc Ctr, Duarte, CA USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Chicago, Chicago, IL 60637 USA. RP Couch, FJ (reprint author), Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. EM Couch.fergus@mayo.edu RI Spurdle, Amanda/A-4978-2011; Andrulis, Irene/E-7267-2013; Jakubowska, Anna/O-8050-2014; Struewing, Jeffery/I-7502-2013; Gronwald, Jacek/A-4576-2017; OI Spurdle, Amanda/0000-0003-1337-7897; Evans, Gareth/0000-0002-8482-5784; Struewing, Jeffery/0000-0002-4848-3334; Gronwald, Jacek/0000-0002-3643-2871; Nathanson, Katherine/0000-0002-6740-0901; Vierkant, Robert/0000-0001-6242-5221; Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Tommiska, Johanna/0000-0001-7958-8262 FU NCI NIH HHS [R01 CA074415, P50 CA116201, P50 CA116201-030002, P50-CA116201, R01 CA074415-10, R01 CA083855, R01 CA083855-08, R01 CA102776, R01 CA102776-04, R01-CA083855, R01-CA102776, R01-CA74415]; NCRR NIH HHS [M01 RR000043, M01 RR000043-440791, M01-RR00043] NR 19 TC 26 Z9 26 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2007 VL 16 IS 7 BP 1416 EP 1421 DI 10.1158/1055-9965.EPI-07-0129 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 192BD UT WOS:000248174800013 PM 17627006 ER PT J AU Birmann, BM Giovannucci, E Rosner, B Anderson, KC Colditz, GA AF Birmann, Brenda M. Giovannucci, Edward Rosner, Bernard Anderson, Kenneth C. Colditz, Graham A. TI Body mass index, physical activity, and risk of multiple myeloma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NATIONAL DEATH INDEX; CELL-GROWTH-FACTOR; UNITED-STATES; FACTOR-I; INTERLEUKIN-6; CANCER; WOMEN; OBESITY; ASSOCIATION; MORTALITY AB Several studies have reported a positive relation of baseline body mass index (BMI) with multiple myeloma, but data on other correlates of energy balance are limited. We undertook the present analyses to further examine the role of energy balance in multiple myeloma etiology in two large prospective cohorts with biennially updated exposure data. We followed members of the Nurses' Health Study and Health Professionals Follow-up Study cohorts from baseline until multiple myeloma diagnosis, death, or 2002. Adult height and current weight were reported at enrollment, and weight every 2 years thereafter. Physical activity was queried at baseline and updated every 2 to 4 years. We computed age-adjusted relative risks MR) of multiple myeloma for categories of BMI and physical activity using Cox proportional hazards regression. We conducted analyses on each cohort separately and on both cohorts combined. We confirmed 215 incident cases of multiple myeloma in the combined cohort of 136,623 individuals (> 2.1 million person-years at risk). BMI was positively associated with multiple myeloma in all analyses. The association was strongest in men with a BMI of >= 30 kg/m2 (versus a BMI of < 22.0 kg/m(2); RR, 2.4; 95% confidence interval, 1.0-6.0) and modest in overweight (BMI, 25-29.9 kg/m(2)) and obese (BMI, >= 30 kg/m(2)) women [versus BMI of < 22.0 kg/m(2); RR (95% confidence interval), 1.6 (1.0-2.7) and 1.2 (0.7-2.2), respectively]. Physical activity was not significantly related to multiple myeloma risk, although an inverse association was suggested in women. In conclusion, obesity seems to have an etiologic role in multiple myeloma, but the role of other correlates of energy balance remains uncertain. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Jerome Lipped Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. RP Birmann, BM (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. EM brenda.birmann@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA10070, CA55075, CA09001, CA87969, K07 CA115687, P01 CA055075, P01 CA087969, T32 CA009001] NR 38 TC 36 Z9 36 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2007 VL 16 IS 7 BP 1474 EP 1478 DI 10.1158/1055-9965.EPI-07-0143 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 192BD UT WOS:000248174800022 PM 17627013 ER PT J AU Young, MRI Neville, BW Chi, AC Lathers, DMR Gillespie, MB Day, TA AF Young, M. Rita I. Neville, Brad W. Chi, Angela C. Lathers, Deane M. R. Gillespie, M. Boyd Day, Terry A. TI Oral premalignant lesions induce immune reactivity to both premalignant oral lesions and head and neck squamous cell carcinoma SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE cytotoxicity; head and neck cancer; HNSCC; oral lesions; premalignant ID EPIDERMAL-GROWTH-FACTOR; PRECANCEROUS LESIONS; CANCER; EXPRESSION; THERAPY; IDENTIFICATION; IMMUNOTHERAPY; LEUKOPLAKIA; RECEPTOR; GENES AB Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy, and despite advances in treatments, the 5-year survival has remained at less than 50%. One treatment strategy is to focus on patients with premalignant oral lesions that carry a high-risk for developing recurrent premalignant lesions and HNSCC disease. As an initial attempt to determine if immune therapy has the potential to be protective in these patients, studies determined if premalignant lesions express tumor antigens that have previously been shown to be expressed on HNSCC. Immunohistochemical analyses showed prominent expression of epidermal growth factor receptor in premalignant lesions, even in lesions with mild dysplasia. MUC-1 and carcinoembryonic antigen were expressed in most patient samples, while NY-ESO-1 was less frequently expressed. Each of these antigens was expressed on HNSCC. This provided the rationale for determining if premalignant oral lesions could be used to stimulate autologous peripheral blood mononuclear leukocytes (PBML) to react against heterologous premalignant lesions and HNSCC. Following sensitization with autologous premalignant lesions, PBML responded to a challenge with either heterologous premalignant oral lesion cells or HNSCC by releasing IFN-gamma. In addition, sensitization with autologous premalignant lesion lysates generated cytolytic activity by both PBML and T cells against allogeneic premalignant lesion cells and HNSCC. These studies show the feasibility of using premalignant oral lesions to stimulate immune reactivity against both premalignant oral lesions as well as HNSCC. C1 Ralph H Johnson Vet Affairs Hosp, Res Serv 151, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Stomatol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Hosp, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@med.va.gov FU NCI NIH HHS [CA85266, CA97813] NR 27 TC 8 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JUL PY 2007 VL 56 IS 7 BP 1077 EP 1086 DI 10.1007/s00262-006-0242-7 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 162NO UT WOS:000246094800012 PM 17096152 ER PT J AU Rege, K Patel, SJ Megeed, Z Yarmush, ML AF Rege, Kaushal Patel, Suraj J. Megeed, Zaki Yarmush, Martin L. TI Amphipathic peptide-based fusion peptides and immunoconjugates for the targeted ablation of prostate cancer cells SO CANCER RESEARCH LA English DT Article ID MEMBRANE ANTIGEN-EXPRESSION; TUMOR-CELLS; LYTIC PEPTIDE; AMINO-ACIDS; ANTIBODY; THERAPY; INTERNALIZATION; PROGRESSION; INHIBITORS; METASTASES AB We describe the design, generation, and in vitro evaluation of targeted amphipathic fusion peptides and immunoconjugates for the ablation of prostate cancer cells. The overexpression of the prostate-specific membrane antigen (PSMA) was exploited as means to specifically deliver cytotoxic peptides to prostate cancer cells. Cationic amphipathic lytic peptides were chosen as cytotoxic agents due to their ability to depolarize mitochondrial membranes and induce apoptosis. Specific delivery of the lytic peptide was facilitated by PSMA-targeting peptides and antibodies. Our results indicate that although the use of PSMA-targeted peptides only modestly enhanced the cytotoxic activity of the lytic peptide, peptide-antibody conjugates were two orders of magnitude more potent than untargeted peptide. In addition to quantifying the cytotoxic activities of the individual constructs, we also investigated the mechanisms of cell death induced by the fusion peptides and immunoconjugates. Although fusion peptides induced oncotic/necrotic death in cells, treatment with immunoconjugates resulted in apoptotic death. In summary, immunoconjugates based on lytic peptides are a promising class of therapeutics for prostate cancer therapy and warrant further investigation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org NR 49 TC 40 Z9 41 U1 1 U2 12 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 JUL 1 PY 2007 VL 67 IS 13 BP 6368 EP 6375 DI 10.1158/0008-5472.CAN-06-3658 PG 8 WC Oncology SC Oncology GA 186II UT WOS:000247772000046 PM 17616696 ER PT J AU Eeckhoute, J Keeton, EK Lupien, M Krum, SA Carroll, JS Brown, M AF Eeckhoute, Jerome Keeton, Erika Krasnickas Lupien, Mathieu Krum, Susan A. Carroll, Jason S. Brown, Myles TI Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; MAMMARY-GLAND; HISTONE MODIFICATIONS; GENE ACTIVATION; NERVOUS-SYSTEM; DIFFERENTIATION; PROMOTER; IDENTIFICATION; MORPHOGENESIS; COACTIVATORS AB The transcription factor GATA-3 is required for normal mammary gland development, and its expression is highly correlated with estrogen receptor alpha (ER alpha) in human breast tumors. However, the functional role of GATA-3 in ER alpha-positive breast cancers is yet to be established. Here, we show that GATA-3 is required for estradiol stimulation of cell cycle progression in breast cancer cells. The role of GATA-3 in estradiol signaling requires the direct positive regulation of the expression of the ER alpha gene itself by GATA-3. GATA-3 binds to two cis-regulatory elements located within the ERa gene, and this is required for RNA polymerase It recruitment to ER alpha promoters. Reciprocally, ER alpha directly stimulates the transcription of the GATA-3 gene, indicating that these two factors are involved in a positive cross-regulatory loop. Moreover, GATA-3 and Er alpha regulate their own expression in breast cancer cells. Hence, this transcriptional coregulatory mechanism accounts for the robust coexpression of GATA-3 and ER alpha in human breast cancers. In addition, these results highlight the crucial role of GATA-3 for the response of ER alpha-positive breast cancers to estradiol. Moreover, they identify GATA-3 as a critical component of the master cell-type-specific transcriptional network including ER alpha and FoxA1 that dictates the phenotype of hormone-dependent breast cancer. C1 Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; krum, susan/D-7282-2013; OI Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU NIDDK NIH HHS [R56DK074967] NR 53 TC 174 Z9 183 U1 0 U2 7 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 JUL 1 PY 2007 VL 67 IS 13 BP 6477 EP 6483 DI 10.1158/0008-5472.CAN-07-0746 PG 7 WC Oncology SC Oncology GA 186II UT WOS:000247772000059 PM 17616709 ER PT J AU Murata, H Ashida, A Takata, M Yamaura, M Bastian, BC Saida, T AF Murata, Hiroshi Ashida, Atsuko Takata, Minoru Yamaura, Maki Bastian, Boris C. Saida, Toshiaki TI Establishment of a novel melanoma cell line SMYM-PRGP showing cytogenetic and biological characteristics of the radial growth phase of acral melanomas SO CANCER SCIENCE LA English DT Article ID CYCLIN D1 GENE; TUMOR PROGRESSION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; AMPLIFICATION; CANCER; OVEREXPRESSION; EXPRESSION; MELANOCYTES; P16(INK4A) AB We established a novel melanoma cell line, SMYM-PRGP, which was non-tumorigenic in vivo, from an acral melanoma in radial growth phase under a low-oxygen environment. SMYM-PRGP was wild-type for known mutation sites in the BRAF and NRAS genes, and showed focal amplification of the human telomerase reverse transcriptase and cyclin D1 genes as well as the fibroblast growth factor-3 and fibroblast growth factor-4 genes. Neither mutation nor copy number loss of the CDKN2A gene was observed. The p16(INK4A) protein was expressed at a level equal to that in normal melanocytes. Among the various melanocyte growth factors added to the culture of SMYM-PRGP cells, endothelin-1 was the strongest growth stimulator, the effect of which was significantly augmented by the addition of calcium chloride. The growth stimulatory effect of endothelin-1 was shown to be mediated via the endothelin B receptor. The protein level of cyclin D1 in SMYM-PRGP cells was approximately 10 times higher than that in normal melanocytes. Although the stimulation with endothelin-1 plus calcium chloride increased cyclin D1 protein levels after 4-6 h, the level of phosphorylated retinoblastoma protein did not increase, suggesting that overexpression of cyclin D1 protein may have little effect on cell cycle progression but rather act as a pro-survival factor. SMYM-PRGP is an excellent tool for investigating the development and progression of acral melanoma. C1 Shinshu Univ, Sch Med, Dept Dermatol, Matsumoto, Nagano 3908621, Japan. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Murata, H (reprint author), Shinshu Univ, Sch Med, Dept Dermatol, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM hmurata@hsp.md.shinshu-u.ac.jp NR 34 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JUL PY 2007 VL 98 IS 7 BP 958 EP 963 DI 10.1111/j.1349-7006.2007.00496.x PG 6 WC Oncology SC Oncology GA 176VI UT WOS:000247112600004 PM 17488338 ER PT J AU Yasmeen, A Hosein, AN Yu, QY Al Moustafa, AE AF Yasmeen, Amber Hosein, Abdel N. Yu, Qunyan Al Moustafa, Ala-Eddin TI Critical role for D-type cyclins in cellular transformation induced by E6/E7 of human papillomavirus type 16 and E6/E7/ErbB-2 cooperation SO CANCER SCIENCE LA English DT Article ID NEOPLASTIC TRANSFORMATION; GENE AMPLIFICATION; CERVICAL-CANCER; UTERINE CERVIX; BREAST-CANCER; HPV TYPE-16; IN-VIVO; CARCINOMA; CELLS; EXPRESSION AB Recently, we reported that E6/E7 of human papillomavirus (HPV) type 16 cooperates with the ErbB-2 receptor to induce cellular transformation of human normal oral epithelial (NOE) and mouse normal embryonic fibroblast (NEF) cells. Furthermore, we demonstrated that cyclin D1 is essential for this transformation induced by E6/E7 and E6/E7/ErbB-2 cooperation using cyclin D1 antisense and knockout (D1(-/-)) cells. To determine the role of all D-type cyclins (D1, D2 and D3) in E6/E7/ErbB-2 cooperation, we examined the effects of E6/E7, ErbB-2 alone and E6/E7/ErbB-2 together in NEF, NEF-D1(-/-), NEF-D2(-/-) and NEF-D3(-/-) cells. We confirm that NEF-E6/E7 and NEF-E6/E7/ErbB-2, but not NEF-ErbB-2 cells, induce colony formation in soft agar and tumor formation in nude mice. We report that E6/E7, ErbB-2 and E6/E7/ErbB-2 together all fail to induce neoplastic transformation of D1(-/-) and D2(-/-) cells in vitro and in vivo. In contrast, E6/E7/ErbB-2 together but neither E6/E7 nor ErbB-2 alone provoke cellular transformation of D3(-/-) cells. Nevertheless, D3(-/-) E6/E7/ErbB-2 cells resulted in up to a 60 and 50% decrease in colony and tumor formation in soft agar and nude mice, respectively, compared with NEF-E6/E7/ErbB-2 cells. Furthermore, using cyclin D2 small interfering RNA we inhibited tumor and colony formation of the human NOE-E6/E7-ErbB-2-transformed cell line; in contrast, cyclin D3 small interfering RNA repressed approximately 50% of colony and 40% of tumor formation of E6/E7/ErbB-2 cooperation in this cell line. These data suggest that cyclins D1, D2 and D3 (to a lesser extent) are important downstream mediators of the cellular transformation induced by E6/E7 and E6/E7/ErbB-2 cooperation in normal cells. Our data imply that anti-D-type cyclin therapies are important in the treatment of human cancers expressing high-risk HPV or HPV/ErbB-2. C1 McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Oncol Human Genet & Med,Program Canc Genet, Montreal, PQ H3T 1E2, Canada. McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Exp Therapeut Canc,Dept Oncol Human Genet & M, Montreal, PQ H3T 1E2, Canada. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Al Moustafa, AE (reprint author), McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Oncol Human Genet & Med,Program Canc Genet, Montreal, PQ H3T 1E2, Canada. EM ala-eddin.almoustafa@mcgill.ca NR 26 TC 7 Z9 7 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JUL PY 2007 VL 98 IS 7 BP 973 EP 977 DI 10.1111/j.1349-7006.2007.00504.x PG 5 WC Oncology SC Oncology GA 176VI UT WOS:000247112600006 PM 17489986 ER PT J AU Kim, SY Hahn, WC AF Kim, So Young Hahn, William C. TI Cancer genomics: integrating form and function SO CARCINOGENESIS LA English DT Review ID COPY NUMBER ALTERATION; HUMAN LUNG CARCINOMAS; BREAST-CANCER; GENE-EXPRESSION; COLORECTAL CANCERS; SIGNALING PATHWAY; RNA INTERFERENCE; HUMAN KINASES; IN-VIVO; SCREEN AB The sequencing of the human genome has formed the foundation with which to develop technologies and reagents to perform true genome-scale biological studies. In particular, the development and increasing application of these high-throughput genome-scale technologies have fundamentally altered the way one can approach the analysis of cancer. It is now possible to imagine studies that interrogate the structure, expression and function of every gene in a comprehensive, highly parallel fashion, permitting the development of multidimensional, global views of cancer. In this review, we focus on recent advances in the application of genomic strategies to the study of cancer, with an emphasis on functional genomics and the prospects for integrating the knowledge gained from these approaches to further develop our understanding of cancer and design better therapeutic strategies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu NR 69 TC 14 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2007 VL 28 IS 7 BP 1387 EP 1392 DI 10.1093/carcin/bgm086 PG 6 WC Oncology SC Oncology GA 199XX UT WOS:000248729600002 PM 17434922 ER PT J AU Hazra, A Wu, K Kraft, P Fuchs, CS Giovannucci, EL Hunter, DJ AF Hazra, Aditi Wu, Kana Kraft, Peter Fuchs, Charles S. Giovannucci, Edward L. Hunter, David J. TI Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nurses' Health Study SO CARCINOGENESIS LA English DT Article ID GENOMIC DNA METHYLATION; METHYLENETETRAHYDROFOLATE REDUCTASE; COLON-CANCER; FOLATE STATUS; TCN2 776C-GREATER-THAN-G; GENE-EXPRESSION; ALCOHOL INTAKE; PLASMA FOLATE; TRANSCOBALAMIN; VITAMIN-B-12 AB Dietary folate and alcohol consumption as well as polymorphic variants in one-carbon metabolism genes may modulate risk of colorectal adenoma through aberrant DNA methylation and altered nucleotide synthesis and repair. We assessed the association of 24 non-synonymous single nucleotide polymorphisms (nsSNPs) in 13 genes in the one-carbon metabolism pathway and risk of colorectal adenoma in 556 incident cases and 557 controls nested in the Nurses' Health Study. Most of the SNPs were not associated with risk of colorectal adenoma. We did, however, observe a modest increased risk among carriers of the transcobalamin (TCN) 11 259 ProlArg + Arg/Arg variant (odds ratio 1.48, 95% confidence interval 1.09-2.02) for colorectal adenoma. The TCN II Pro259Arg polymorphism may affect TCN binding and transport of vitamin B12 and thus warrants further investigation of its biological function. In addition, the methionine synthase reductase (MTRR) Arg415Cys and MTRR Ser284Thr variant carriers, also in the vitamin B12 pathway, have suggestive associations with advanced colorectal adenoma (defined as being larger than 1 cm, villous, tubular-villous or carcinoma in situ histology). We observed significant evidence for departure from multiplicative interaction for the betaine-homocysteine methyltransferase (BHM7) Arg239GIn with dietary methyl status (based on intake of dietary folate, methionine and alcohol intake) in relation to colorectal adenoma; no such interaction was observed for the other 23 SNPs. Further investigation is required to validate the association of the polymorphisms in the one-carbon metabolic genes and risk of colorectal adenoma. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hazra, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. EM ahazra@hsph.harvard.edu FU NCI NIH HHS [T-32 CA 09001-30, CA87969, P01-CA087969, U54 CA100971] NR 60 TC 40 Z9 41 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2007 VL 28 IS 7 BP 1510 EP 1519 DI 10.1093/carcin/bgm062 PG 10 WC Oncology SC Oncology GA 199XX UT WOS:000248729600020 PM 17389618 ER PT J AU Gould, D Patel, A Becker, G Connors, B Cardella, J Dawson, S Glaiberman, C Kessel, D Lee, M Lewandowski, W Phillips, R Reekers, J Sacks, D Sapoval, M Scerbo, M AF Gould, Derek Patel, Aalpen Becker, Gary Connors, Buddy Cardella, John Dawson, Steven Glaiberman, Craig Kessel, David Lee, Mick Lewandowski, William Phillips, Roger Reekers, Jim Sacks, David Sapoval, Marc Scerbo, Mark TI SIR/RSNA/CIRSE joint medical simulation task force strategic plan: Executive summary SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 Royal Liverpool Univ Trust, Dept Radiol, Liverpool, Merseyside, England. Univ Penn, Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. Univ Arizona, Coll Med, Dept Radiol, Tucson, AZ 85724 USA. Radiol Assoc Sacramento, Sacramento, CA USA. Tufts Univ, Sch Med, Baystate Hlth Syst, Dept Radiol, Springfield, MA 01199 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Leeds Teaching Hosp, Leeds, W Yorkshire, England. Royal Coll Surgeons Ireland, Beaumont Hosp, Dept Radiol, Dublin 2, Ireland. Wiiliam E Lewandowski Consulting, Daytona Beach, FL USA. Univ Hull, Dept Comp Sci, Kingston Upon Hull HU6 7RX, N Humberside, England. Univ Amsterdam, Acad Med Ctr, Dept Radiol, NL-1105 AZ Amsterdam, Netherlands. Reading Hosp Med Ctr, Dept Radiol, Reading, PA USA. Hop Europeen Georges Pompidou, Dept Radiol, Paris, France. Old Dominion Univ, Dept Psychol, Norfolk, VA USA. RP Gould, D (reprint author), Royal Liverpool Univ Trust, Dept Radiol, Liverpool, Merseyside, England. EM dgould@liv.ac.uk NR 4 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUL PY 2007 VL 30 IS 4 BP 551 EP 554 DI 10.1007/s00270-007-9103-9 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 201KU UT WOS:000248831000001 PM 17587079 ER PT J AU Klein, AJ Messenger, JC Casserly, IP AF Klein, Andrew J. Messenger, John C. Casserly, Ivan P. TI Contemporary management of acute lower extremity ischemia following percutaneous coronary and cardiac interventional procedures using femoral access - A case series and discussion SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE complication; percutaneous coronary intervention; vascular closure device; endovascular therapy; acute limb ischemia ID PUNCTURE CLOSURE DEVICE; VASCULAR COMPLICATIONS; ARTERIAL HEMOSTASIS; MANUAL COMPRESSION; RANDOMIZED TRIAL; CATHETERIZATION; SUTURE; ANGIOPLASTY; ANGIO-SEAL(TM); ANGIOGRAPHY AB New onset of acute lower extremity ischemia following percutaneous coronary and cardiac interventional procedures using femoral access is an important clinical entity that requires emergent assessment to determine the precise etiology and institute appropriate therapy. We report four cases of this clinical event from our catheterization laboratories that serve to highlight the most frequent etiologies, the importance of immediate diagnostic angiography, and the potential for endovascular techniques to effectively manage this complication. (c) 2007 Wiley-Liss, Inc. C1 Univ Colorado Hosp, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. RP Casserly, IP (reprint author), Univ Colorado Hosp, 4200 E 9th Ave,B-132, Denver, CO 80262 USA. EM ivan.casserly@uchsc.edu NR 24 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL 1 PY 2007 VL 70 IS 1 BP 129 EP 137 DI 10.1002/ccd.21158 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 186XR UT WOS:000247812400024 PM 17585383 ER PT J AU Klein, AJ Messenger, JC Casserly, IP AF Klein, Andrew J. Messenger, John C. Casserly, Ivan P. TI Endovascular treatment of intra-aortic balloon pump-induced acute limb ischemia SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE intra-aortic balloon pump; acute limb ischemia; complication; endovascular therapy ID VASCULAR COMPLICATIONS; RISK ANALYSIS; FOLLOW-UP; OPERATIONS AB The development of acute limb ischemia in patients following intra-aortic balloon pump (IABP) placement remains a frequent event that presents a significant management challenge. We report two recent cases of this clinical event from our institution, which demonstrate that endovascular therapies may be used to treat acute limb ischemia in this setting without requiring removal of the IABP. (c) 2007 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Serv Denver, Div Cardiol, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. RP Casserly, IP (reprint author), Univ Colorado, Hlth Serv Denver, Div Cardiol, 4200 E 9th Ave, Denver, CO 80262 USA. EM ivan.casserly@uchsc.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL 1 PY 2007 VL 70 IS 1 BP 138 EP 142 DI 10.1002/ccd.21177 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 186XR UT WOS:000247812400025 PM 17585391 ER PT J AU Sablina, AA Hahn, WC AF Sablina, Anna A. Hahn, William C. TI The Role of PP2A A Subunits in Tumor Suppression SO CELL ADHESION & MIGRATION LA English DT Article DE protein phosphatase 2A; RalA; cancer; transformation AB The protein phosphatase 2A (PP2A) family of heterotrimeric serine-threonine phosphatases participates in human cell transformation. Each functional PP2A complex contains one structural A subunit (A alpha or A beta), and mutations of both are found to occur at low frequency in human tumors. We have shown that A alpha functions as haploinsufficient tumor suppressor gene by regulating in part phosphatidylinositol 3-kinase (Pl3K) signaling. In contrast, loss of A beta function due to biallelic alterations contributes to cancer progression through dysregulation of small GTPase RalA activity. These observations provide evidence that dysfunction of particular PP2A complexes regulate specific phosphorylation event necessary for cancer initiation. C1 [Sablina, Anna A.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sablina, Anna A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sablina, Anna A.; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Hahn, WC (reprint author), 44 Binney St, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu NR 17 TC 20 Z9 23 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6918 J9 CELL ADHES MIGR JI Celll Adhes. Migr. PD JUL-SEP PY 2007 VL 1 IS 3 BP 140 EP 141 DI 10.4161/cam.1.3.4986 PG 2 WC Cell Biology SC Cell Biology GA V21US UT WOS:000208233100007 PM 19262135 ER PT J AU Hussein, MR AF Hussein, Mahmoud R. TI Expression of KIT receptor tyrosine kinase protein in normal human skin: Preliminary observations SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE skin; KIT; melanocytes; keratinocytes ID HUMAN SCALP SKIN; C-KIT; GROWTH-FACTOR; METASTATIC MELANOMA; MALIGNANT-MELANOMA; IMATINIB MESYLATE; CLINICAL-EFFICACY; HAIR-FOLLICLES; CELLS; CD117 AB KIT proto-oncogene is a receptor tyrosine kinase critical for signal transduction in several cell types. An understanding of KIT distribution in normal skin may reveal new insights into its implication in cutaneous biology and its associated disease states. This study examines expression patterns of KIT protein in normal human skin. KIT protein expression was examined in 50 specimens of normal human skin using specific antibodies (CD 117) and immunoperoxidase staining methods. KIT protein expression was seen in keratinocytes (stratum basale), melanocytes, mast cells, and in both sebaceous and sweat glands. In contrast, KIT protein expression was absent in stratum spinosum, stratum granulosum, stratum comeum, blood vessels and arrector pili muscle. Thus, the expression of KIT protein in normal human skin suggests its possible role in regulation of cutaneous development and function. (c) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. C1 Assiut Univ, Sch Med, Dept Pathol, Assiut, Egypt. Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assiut Univ, Sch Med, Dept Pathol, Assiut, Egypt. EM mrh17@swissinfo.org NR 23 TC 6 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD JUL PY 2007 VL 31 IS 7 BP 748 EP 751 DI 10.1016/j.cellbi.2006.12.006 PG 4 WC Cell Biology SC Cell Biology GA 179RT UT WOS:000247308500014 PM 17337216 ER PT J AU Seale, P Kajimura, S Yang, W Chin, S Rohas, LM Uldry, M Tavernier, G Langin, D Spiegelman, BM AF Seale, Patrick Kajimura, Shingo Yang, Wenli Chin, Sherry Rohas, Lindsay M. Uldry, Marc Tavernier, Genevieve Langin, Dominique Spiegelman, Bruce M. TI Transcriptional control of brown fat determination by PRDM16 SO CELL METABOLISM LA English DT Article ID UNCOUPLING PROTEIN GENE; WHITE ADIPOSE TISSUES; DIET-INDUCED OBESITY; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; TRANSGENIC MICE; MITOCHONDRIAL BIOGENESIS; COACTIVATOR PGC-1-ALPHA; OXIDATIVE-METABOLISM; COREPRESSOR RIP140 AB Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1 alpha, UCP1, and type 2 deiodinase (Dio2) expression and a remarkable increase in uncoupled respiration. Transgenic expression of PRDM16 at physiological levels in white fat depots stimulates the formation of brown fat cells. Depletion of PRDM16 through shRNA expression in brown fat cells causes a near total loss of the brown characteristics. PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1 alpha and PGC-1 beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. Rangueil Inst Mol Med, INSERM, U858, Obes Res Lab, F-31432 Toulouse, France. Univ Toulouse 3, Louis Bugnard Inst, IFR31, F-31432 Toulouse, France. CHU Toulouse, Lab Clin Biochem, Biol Inst Purpan, F-31059 Toulouse, France. RP Spiegelman, BM (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu OI Langin, Dominique/0000-0002-2669-7825 FU NIDDK NIH HHS [DK31405-24, R01 DK031405, R37 DK031405, R37 DK031405-25] NR 88 TC 424 Z9 453 U1 7 U2 40 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUL PY 2007 VL 6 IS 1 BP 38 EP 54 DI 10.1016/j.cmet.2007.06.001 PG 17 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 189JJ UT WOS:000247984900006 PM 17618855 ER PT J AU Sosa, MAG De Gasperi, R Rocher, AB Perez, GM Simons, K Cruz, DE Hof, PR Elder, GA AF Sosa, Miguel A. Gama De Gasperi, Rita Rocher, Anne B. Perez, Gissel M. Simons, Kella Cruz, Daniel E. Hof, Patrick R. Elder, Gregory A. TI Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact SO CELL RESEARCH LA English DT Article DE differentiation; culture; endothelial cells; neuroepithelial cells ID VESSEL NAVIGATION; NERVOUS SYSTEMS; ANGIOGENESIS; MECHANISMS; GUIDANCE AB Neurovascular interactions are crucial for the normal development of the central nervous system. To study such interactions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and endothelial cell fractions from embryonic mouse brains. Depending on the culture conditions endothelial cells were found to favor maintenance of the neuroprogenitor phenotype through the production of soluble factors, or to promote neuronal differentiation of neural progenitors through direct contact. These apparently opposing effects could reflect differential cellular interactions needed for the proper development of the brain. C1 NYU, Mt Sinai Sch Med, Dept Psychiat, New York, NY 10016 USA. James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. NYU, Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. RP Sosa, MAG (reprint author), NYU, Mt Sinai Sch Med, Dept Psychiat, 130 W Kingsbridge Rd, New York, NY 10016 USA. EM miguel.gama-sosa@mssm.edu NR 18 TC 16 Z9 16 U1 0 U2 1 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JUL PY 2007 VL 17 IS 7 BP 619 EP 626 DI 10.1038/cr.2007.53 PG 8 WC Cell Biology SC Cell Biology GA 203SW UT WOS:000248995300006 ER PT J AU Maherali, N Sridharan, R Xie, W Utikal, J Eminli, S Arnold, K Stadtfeld, M Yachechko, R Tchieu, J Jaenisch, R Plath, K Hochedlinger, K AF Maherali, Nimet Sridharan, Rupa Xie, Wei Utikal, Jochen Eminli, Sarah Arnold, Katrin Stadtfeld, Matthias Yachechko, Robin Tchieu, Jason Jaenisch, Rudolf Plath, Kathrin Hochedlinger, Konrad TI Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution SO CELL STEM CELL LA English DT Article ID EMBRYONIC STEM-CELLS; INACTIVE X-CHROMOSOME; DEVELOPMENTAL REGULATORS; SOMATIC-CELLS; ES CELLS; MOUSE; PLURIPOTENCY; METHYLATION; NANOG; POLYCOMB AB Ectopic expression of the four transcription factors Oct4, Sox2, c-Myc, and Klf4 is sufficient to confer a pluripotent state upon the fibroblast genome, generating induced pluripotent stem (PS) cells. It remains unknown if nuclear reprogramming induced by these four factors globally resets epigenetic differences between differentiated and pluripotent cells. Here, using novel selection approaches, we have generated PS cells from fibroblasts to characterize their epigenetic state. Female PS cells showed reactivation of a somatically silenced X chromosome and underwent random X inactivation upon differentiation. Genome-wide analysis of two key histone modifications indicated that PS cells are highly similar to ES cells. Consistent with these observations, PS cells gave rise to viable high-degree chimeras with contribution to the germline. These data show that transcription factor-induced reprogramming leads to the global reversion of the somatic epigenome into an ES-like state. Our results provide a paradigm for studying the epigenetic modifications that accompany nuclear reprogramming and suggest that abnormal epigenetic reprogramming does not pose a problem for the potential therapeutic applications of PS cells. C1 Univ Calif Los Angeles, Johnson Comprehensive Canc Ctr, Inst Stem Cell Biol & Med, Sch Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. MIT, Whitehead Inst, Dept Biol, Cambridge, MA 02142 USA. RP Plath, K (reprint author), Univ Calif Los Angeles, Johnson Comprehensive Canc Ctr, Inst Stem Cell Biol & Med, Sch Med, Los Angeles, CA 90095 USA. EM kplath@mednet.ucla.edu; khochedlinger@helix.mgh.harvard.edu OI Utikal, Jochen/0000-0001-5316-0241; Stadtfeld, Matthias/0000-0002-5852-9906 FU NIH HHS [DP2 OD003266] NR 35 TC 1033 Z9 1096 U1 10 U2 119 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 JUL PY 2007 VL 1 IS 1 BP 55 EP 70 DI 10.1016/j.stem.2007.05.014 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 230JK UT WOS:000250872600002 PM 18371336 ER PT J AU Aminoff, E Gronau, N Bar, M AF Aminoff, E. Gronau, N. Bar, M. TI The parahippocampal cortex mediates spatial and nonspatial associations SO CEREBRAL CORTEX LA English DT Article DE associations; context; episodic memory; parahippocampal; PPA; spatial memory ID TEMPORAL-LOBE ACTIVATION; LONG-TERM-MEMORY; PERIRHINAL CORTEX; RECOGNITION MEMORY; DECLARATIVE MEMORY; HIPPOCAMPAL SYSTEM; ENCODING ACTIVITY; ITEM RECOGNITION; BRAIN ACTIVITY; CONTEXT AB The parahippocampal cortex (PHC) has been implicated in the processing of place-related information. It has also been implicated in episodic memory, even for items that are not related to unique places. How could the same cortical region mediate such seemingly different cognitive processes? Both processes rely on contextual associations, and we therefore propose that the PHC should be viewed not as exclusively dedicated for analyzing place-related information, or as solely processing episodic memories, but instead as more generally playing a central role in contextual associative processing. To test this proposal, we created a novel learning paradigm to form new associations among meaningless visual patterns. These new associations were created to emulate either spatial or nonspatial contexts. Both spatial and nonspatial associations activated the PHC more than noncontextual items. Moreover, items from spatial contexts activated the posterior part of the PHC, whereas items from nonspatial contexts activated the anterior PHC. Therefore, we show that the PHC plays a role of processing contextual associations in general, and that these associations are not restricted to spatial information. By modifying the existing view of the PHC function accordingly, the seemingly contradicting processes that activate it can be reconciled under one overarching framework. C1 Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Bar, M (reprint author), Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM bar@nmr.mgh.harvard.edu OI Aminoff, Elissa/0000-0002-6455-8930 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [T32MH070328]; NINDS NIH HHS [NS050615, R01 NS044319] NR 74 TC 157 Z9 159 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 2007 VL 17 IS 7 BP 1493 EP 1503 DI 10.1093/cercor/bhl078 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 180FX UT WOS:000247349000001 PM 16990438 ER PT J AU Hoppe, H Kaufman, JA Barton, RE Petersen, BD Lakin, PC DeLoughery, TG Irani, Z Yavuz, K Keller, FS AF Hoppe, Hanno Kaufman, John A. Barton, Robert E. Petersen, Bryan D. Lakin, Paul C. DeLoughery, Thomas G. Irani, Zubin Yavuz, Kivilcim Keller, Frederick S. TI Safety of inferior vena cava filter retrieval in anticoagulated patients SO CHEST LA English DT Article DE pulmonary embolism; vena cava filters; venous thrombosis ID RECURRENT VENOUS THROMBOEMBOLISM; PULMONARY-EMBOLISM; FOLLOW-UP; CLINICAL-EXPERIENCE; REPORTING STANDARDS; RISK; PREVENTION; PLACEMENT; TEMPORARY; THERAPY AB Purpose: To evaluate the safety of inferior vena cava (IVC) filter retrieval in therapeutically anticoagulated patients in comparison to prophylactically or not therapeutically anticoagulated patients with respect to retrieval-related hemorrhagic complications. Materials and methods: This was a retrospective study of 115 consecutive attempted IVC filter retrievals in 110 patients. Filter retrievals were stratified as performed in patients who were therapeutically anticoagulated (group 1), prophylactically anticoagulated (group 2), or not therapeutically anticoagulated (group 3). The collected data included anticoagulant and antiplatelet medications (type, form and duration of administration, dosage) at the time of retrieval. Phone interviews and chart review was performed for the international normalized ratio (INR), activated partial thromboplastin time, platelet count, infusion of blood products, and retrieval-related hemorrhagic complications. Results: Group I included 65 attempted filter retrievals in 61 therapeutically anticoagulated patients by measured INR or dosing when receiving low-molecular-weight heparin (LMWH). Four retrievals were not successful. In patients receiving oral anticoagulation, the median INR was 2.35 (range, 2 to 8). Group 2 comprised 23 successful filter retrievals in 22 patients receiving a prophylactic dose of LMWH. Group 3 included 27 attempted filter retrievals in 27 patients not receiving therapeutic anticoagulation. Six retrievals were not successful. Five patients were receiving oral anticoagulation with a subtherapeutic INR (median, 1.49; range, 1.16 to 1.69). No anticoagulation medication was administered in 22 patients. In none of the groups were hemorrhagic complications related to the retrieval procedures identified. Conclusions: These results suggest that retrieval of vena cava filters in anticoagulated patients is safe. Interruption or reversal of anticoagulation for the retrieval of vena cava filters is not indicated. C1 Oregon Hlth & Sci Univ, Dotter Intervent Inst, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP Hoppe, H (reprint author), Oregon Hlth & Sci Univ, Dotter Intervent Inst, L-605,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM hoppeh@ohsu.edu NR 24 TC 18 Z9 19 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2007 VL 132 IS 1 BP 31 EP 36 DI 10.1378/chest.06-2897 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 191OL UT WOS:000248140600009 PM 17505040 ER PT J AU Counter, SA Buchanan, LH Ortega, F Rifai, N Shannon, MW AF Counter, S. Allen Buchanan, Leo H. Ortega, Fernando Rifai, Nader Shannon, Michael W. TI Comparative analysis of zinc protoporphyrin and blood lead levels in lead-exposed Andean children SO CLINICAL BIOCHEMISTRY LA English DT Article DE lead; zinc protoporphyrin; hemoglobin; iron deficiency; anemia; blood; Andes ID IRON-DEFICIENCY; INTOXICATION; HEMOGLOBIN; ASSOCIATION; ACHIEVEMENT; IMPAIRMENT AB Objectives: The objective of this study was to investigate the zinc protoporphyrin/heme ratio (ZPP/heme) as a biomarker for chronic lead (Ph) poisoning in children with a history of high Pb exposure. Design and methods: ZPP/heme ratio was measured in blood samples from 78 children (44 females and 34 males) with persistent Ph exposure from Pb glazing of ceramics in a local cottage industry in the Andes Mountains of Ecuador. Results: Mean blood lead (PbB) level was 26.4 mu g/dL (SD: 23.2; range: 4.0-107.0), and the mean ZPP/heme ratio was 152.4 mu mol/mol (SD: 190.6; range: 36.0-1064.0). A regression analysis of PbB level and ZPP/heme ratio revealed a significant association (r=0.761, p=< 0.0001), with the logZPP showing a higher correlation with PbB (r=0.869,p=< 0.0001). The ZZP/heme ratio decreased significantly with increasing age (ANOVA, p=0.030). The mean ZPP/heme ratios for females and males were 139.6 and 169.0 mu mol/mol, respectively, and were not statistically different (t-test, p=0.504). Conclusion: The elevated ZPP/heme ratios, coupled with high PbB levels observed in this cohort of Andean children of Pb-glazing workers, suggest chronic Pb intoxication and probable iron deficiency. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Shriver Ctr, Dept Pediat, Waltham, MA USA. Harvard Univ, Hlth Serv, Dept Otolaryngol, Cambridge, MA 02138 USA. Univ San Francisco, Coll Hlth Sci, Integrated Community Dev Dept, Quito, Ecuador. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu NR 31 TC 11 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD JUL PY 2007 VL 40 IS 11 BP 787 EP 792 DI 10.1016/j.clinbiochem.2007.03.003 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 187IS UT WOS:000247841600006 PM 17462618 ER PT J AU Jinushi, M Dranoff, G AF Jinushi, Masahisa Dranoff, Glenn TI Triggering tumor immunity through angiogenesis targeting SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; REGULATORY T-CELLS; THERAPEUTIC IMPLICATIONS; VASCULAR NORMALIZATION; CANCER; BLOCKADE; IMMUNOTHERAPY; FIBROBLASTS; ANGIOPOIETIN-1; PROGENITORS C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 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 RI Jinushi, Masahisa/A-4311-2012 NR 32 TC 8 Z9 9 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2007 VL 13 IS 13 BP 3762 EP 3764 DI 10.1158/1078-0432.CCR-07-0880 PG 3 WC Oncology SC Oncology GA 186IT UT WOS:000247773100002 PM 17606704 ER PT J AU Younes, H Leleu, X Hatjiharissi, E Moreau, AS Hideshima, T Richardson, P Anderson, KC Ghobrial, IM AF Younes, Hashem Leleu, Xavier Hatjiharissi, Evdoxia Moreau, Anne-Sophie Hideshima, Teru Richardson, Paul Anderson, Kenneth C. Ghobrial, Irene M. TI Targeting the phosphatidylinositol 3-kinase pathway in multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID C-BETA INHIBITOR; PHOSPHOINOSITIDE 3-KINASE; AKT PATHWAY; IN-VIVO; MAMMALIAN TARGET; SIGNALING PATHWAY; CELL-SURVIVAL; SYNERGISTIC ACTIVITY; CANCER-THERAPY; RAPAMYCIN MTOR AB Multiple myeloma is a plasma cell neoplasm with a median survival of 3 to 5 years. Recent advances have improved patient outlook, but the disease remains incurable. Therefore, continued efforts to develop new therapies that target aberrant signaling pathways are needed. The phosphatidylinositol 3-kinase pathway regulates apoptosis, cell cycle regulation, and tumor proliferation. This pathway is constitutively activated in multiple myeloma and its inhibition induces apoptosis. Advances in understanding the signaling cascades mediating proliferation and survival of multiple myeloma cells have markedly improved the treatment of this disease. In this article, we review the role of the phosphatidylinositol 3-kinase/Akt pathway in the pathogenesis' of multiple myeloma and the potential therapeutic implications of targeting this pathway in the treatment of multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Dept Internal Med, Div Hematol Oncol, Pittsburgh, PA USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu NR 65 TC 49 Z9 53 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2007 VL 13 IS 13 BP 3771 EP 3775 DI 10.1158/1078-0432.CCR-06-2921 PG 5 WC Oncology SC Oncology GA 186IT UT WOS:000247773100004 PM 17606706 ER PT J AU Kwabi-Addo, B Chung, WB Shen, L Ittmann, M Wheeler, T Jelinek, J Issa, JPJ AF Kwabi-Addo, Bernard Chung, Woonbok Shen, Lanlan Ittmann, Michael Wheeler, Thomas Jelinek, Jaroslav Issa, Jean-Pierre J. TI Age-related DNA methylation changes in normal human prostate tissues SO CLINICAL CANCER RESEARCH LA English DT Article ID CPG-ISLAND METHYLATION; TUMOR-SUPPRESSOR GENE; INTRAEPITHELIAL NEOPLASIA; HUMAN CANCERS; HYPERMETHYLATION; INACTIVATION; ESTROGEN; GROWTH; SERUM AB Purpose: Prostate cancer is a leading cause of cancer death among the aging male population but the mechanism underlying this association is unclear. Aberrant methylation of promoter CpG islands is associated with silencing of genes and age-dependent methylation of several genes has been proposed as a risk factor for sporadic cancer. We examined the extent of gene methylation in pathologically normal human prostate as a function of age. Experimental Design: We used pyrosequencing to quantitatively analyze the methylation status of nine CpG islands in normal prostate tissue DNA from 45 organ donors and 45 patients who had undergone cystoprostatectomy for bladder cancer. We also analyzed 12 pairs of matched benign and prostate cancer tissue DNA from patients with prostate cancer. Results: Linear regression analysis revealed a significant increase in promoter methylation levels correlating with age for CpG islands at RAR beta 2 (r = 0.4; P < 0.0001), RASSF1A (r = 0.27; P = 0.01), GSTP1 (r = 0.59; P < 0.0001), NKX2-5 (r = 0.27; P = 0.008), and ESR1 (r = 0.244; P = 0.023) in the normal prostate tissue samples studied. A calculated average methylation (z score) at all nine CpG loci analyzed in the normal prostate tissues showed a strong correlation with age (r = 0.6; P < 0.001). Comparison of the methylation level for the matched benign and prostate cancer tissues from individual patients with prostate cancer showed significantly higher methylation in the prostate cancer tissue samples for RAR beta 2 (P < 0.001), RASSF1A (P = 0.005), GSTP1 (P < 0.001), NKX2-5 (P = 0.003), ESR1 (P = 0.016), and CLSTN1 (P = 0.01). Conclusions: Our findings show aberrant hypermethylation as a function of age in the normal prostate tissues. Such age-related methylation may precede and predispose to full-blown malignancy. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Kwabi-Addo, B (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM bernardk@bcm.tmc.edu RI Jelinek, Jaroslav/A-8476-2008; Jelinek, Jaroslav/D-2282-2012; Kwabi-Addo, Bernard/A-6993-2016 OI Jelinek, Jaroslav/0000-0002-2533-0220; Kwabi-Addo, Bernard/0000-0003-3692-6350 FU NCI NIH HHS [P50CA058204, PC040326] NR 29 TC 134 Z9 143 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2007 VL 13 IS 13 BP 3796 EP 3802 DI 10.1158/1078-0432.CCR-07-0085 PG 7 WC Oncology SC Oncology GA 186IT UT WOS:000247773100008 PM 17606710 ER PT J AU Poh, KK Avelar, E Hua, LQ King, ME AF Poh, Kian Keong Avelar, Erick Hua, Lanqi King, Mary Etta TI Cardiac metastases from malignant melanoma SO CLINICAL CARDIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Poh, KK (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Blake 2,55 Fruit St, Boston, MA 02114 USA. EM doctorpoh@yahoo.com NR 1 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2007 VL 30 IS 7 BP 359 EP 360 DI 10.1002/clc.20051 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 192NG UT WOS:000248208200009 PM 17563887 ER PT J AU Travison, TG O'Donnell, AB Araujo, AB Matsumoto, AM McKinlay, JB AF Travison, Thomas G. O'Donnell, Amy B. Araujo, Andre B. Matsumoto, Alvin M. McKinlay, John B. TI Cortisol levels and measures of body composition in middle-aged and older men SO CLINICAL ENDOCRINOLOGY LA English DT Article ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; FAT DISTRIBUTION; METABOLIC SYNDROME; CUSHINGS-SYNDROME; BLOOD-PRESSURE; RISK-FACTORS; OBESITY; SECRETION; PREVALENCE; HEALTH AB Introduction Similarities in the symptomatic expressions of excess adiposity and hypercortisolaemic conditions suggest that elevated glucocorticoid exposure may influence the pathogenesis of obesity. Circulating cortisol levels are not typically elevated in obese subjects, but data from large prospective samples are rare. We undertook an analysis to determine both cross-sectional and longitudinal associations between body composition and serum cortisol concentrations in a randomly chosen group of 999 community-dwelling men, aged 40-79 years. Methods Data were obtained from the two follow-up waves of the Massachusetts Male Ageing Study (T2: 1995-97; T3: 2002-04). Partial correlation and multivariate regression analyses were used to estimate cross-sectional (T2) and longitudinal associations between serum cortisol concentrations and a range of measures of subjects' body composition, including weight, body mass index (BMI), waist circumference (WC), waist-to-hip girth ratio (WHR), and percentage body fat (measured by bioelectrical impedance at T3); similar analyses were conducted to assess the association between change (T2 to T3) in serum cortisol and simultaneous change in body composition parameters. Results We observed weak negative associations between cortisol concentrations and all body composition parameters, with the exception of percentage body fat. Longitudinal results demonstrated similar relationships but associations were of lesser magnitude. T2 cortisol concentrations were not associated with change in body composition over time, whereas T2 body size was positively associated with longitudinal changes in cortisol concentrations, providing limited evidence that weight change drives changes in cortisol concentrations, rather than vice versa. Results were unchanged when age and other covariate effects were controlled. Conclusions Circulating cortisol concentrations are somewhat lower in obese than in nonobese community-dwelling men. There is some evidence that excess adiposity presages increases in cortisol concentrations, rather than the reverse. However, this observation should be greeted with caution, as age-related weight loss - and not gain - was associated with simultaneous increases in serum cortisol concentrations. C1 New England Res Inst, Watertown, MA 02472 USA. Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst,Dept Med, Seattle, WA 98195 USA. RP Travison, TG (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM ttravison@neriscience.com RI Travison, Thomas/C-7098-2011 FU NIA NIH HHS [AG04673]; NIDDK NIH HHS [DK51345, DK44995] NR 42 TC 43 Z9 44 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 2007 VL 67 IS 1 BP 71 EP 77 DI 10.1111/j.1365-2265.2007.02837.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180DC UT WOS:000247339300011 PM 17466009 ER PT J AU Overberger, P Pesacreta, M Palevsky, PM AF Overberger, Pamela Pesacreta, Matthew Palevsky, Paul M. CA VA NIH Acute Renal Failure Trial N TI Management of renal replacement therapy in acute kidney injury: A survey of practitioner prescribing practices SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; PATIENT SAFETY; TIDAL VOLUMES; TRIAL DESIGN; FAILURE; DIALYSIS; CARE AB Background: Data on current practices for management of renal replacement therapy (RRT) in acute kidney injury (AKI) are limited, particularly with regard to the dosing of therapy. Design, setting, participants, and measurements: A survey was conducted of practitioners at the 27 study sites that participate in the Veterans Affairs/National Institutes of Health Acute Renal Trial Network (ATN) Study before initiation of patient enrollment for ascertainment of the local prevailing practices for management of RRT in critically ill patients with AKI. Surveys were returned from 130 practitioners at 26 of 27 study sites; the remaining study site provided aggregate data. Results: Intermittent hemodialysis and continuous RRT were the most commonly used modalities of RRT, with sustained low-efficiency dialysis and other "hybrid" treatments used in fewer than 10% of patients. Intermittent hemodialysis was most commonly provided on a thrice-weekly or every-other-day schedule, with only infrequent assessment of the delivered dosage of therapy. Most practitioners reported that they did not dose continuous RRT on the basis of patient weight. The average prescribed dosage of therapy corresponded to a weight-based dosage of no more than 20 to 25 ml/kg per h. Conclusions: These results provide insight into clinical management of RRT and provide normative data for evaluation of the design of ongoing clinical trials. C1 VA Pittsburgh Healthcare Syst, Res Serv, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Res Serv, Room 7E123,111F-U,Univ Dr Div, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Batuman, Vecihi/0000-0002-1800-9009; Palevsky, Paul/0000-0002-7334-5400 FU NIDDK NIH HHS [Y01 DK3508-03, Y01 DK003508, Y01 DK3508-01, Y01 DK3508-02, Y1-DK-3508-01] NR 21 TC 65 Z9 71 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2007 VL 2 IS 4 BP 623 EP 630 DI 10.2215/CJN.00780207 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 184AE UT WOS:000247612700003 PM 17699474 ER PT J AU Mohamed, OHK Wahba, IM Watnick, S Earle, SB Bennett, WM Ayres, JW Munar, MY AF Mohamed, Osama Hussein Kamel Wahba, Ihab M. Watnick, Suzanne Earle, Sandra B. Bennett, William M. Ayres, James W. Munar, Myrna Y. TI Administration of tobramycin in the beginning of the hemodialysis session: A novel intradialytic dosing regimen SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RESIDUAL RENAL-FUNCTION; PERITONEAL-DIALYSIS PATIENTS; AMINOGLYCOSIDE THERAPY; RECEIVING HEMODIALYSIS; RELATIVE CONTRIBUTION; VESTIBULAR TOXICITY; GENTAMICIN; CLEARANCE; RATES; PHARMACOKINETICS AB Background: Aminoglycoside antibiotic efficacy is related to peak concentration (C-max) and postantibiotic effect, whereas toxicity is directly related to body exposure as measured by area under the serum concentration versus time curve (AUC). On the basis of pharmacokinetic simulation models, tobramycin administration during the first 30 min of high-flux hemodialysis achieves similar C-max but significantly lower AUC and prehemodialysis concentrations compared with conventional dosing in the last 30 min of hemodialysis. Design, setting, participants, and measurements: To test this hypothesis, a pilot study in which five adult chronic hemodialysis patients who were undergoing high-flux dialysis received one dose of tobramycin 1.5 mg/kg intravenously during the first or last 30 min of hemodialysis was conducted. After a 1-mo washout period, patients crossed over to the other treatment schedule. Tobramycin serum concentrations were measured to determine C-max, interdialytic and intradialytic elimination rate constants and half-lives, AUC, and clearance. Results: Tobramycin administration during the first and last 30 min of hemodialysis resulted in similar C-max of 5.63 +/- 0.49 and 5.83 +/- 0.67 mg/L (P > 0.05) but significantly lower prehemodialysis concentrations of 0.16 +/- 0.09 and 2.44 +/- 0.43 mg/L (P < 0.001) and AUC of 21.06 and 179.23 +/- 25.84 mg/h per L (P < 0.001), respectively. Conclusions: Tobramycin administration during the first 30 min of hemodialysis results in similar C-max but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity. C1 Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, Dept Pharm,Dept Pharm Practice, Portland, OR 97239 USA. Oregon State Univ, Coll Pharm, Dept Pharmaceut Sci, Corvallis, OR 97331 USA. Legacy Good Samaritan Hosp, Portland, OR USA. Findlay Univ, Sch Pharm, Dept Pharm Practice, Findlay, OH USA. Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. Cairo Univ, Dept Pharmaceut, Fac Pharm, Cairo, Egypt. RP Munar, MY (reprint author), Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, Dept Pharm,Dept Pharm Practice, Portland Campus,3303 SW Bond Ave,Mail Code CH12C, Portland, OR 97239 USA. EM munarm@ohsu.edu NR 21 TC 13 Z9 13 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2007 VL 2 IS 4 BP 694 EP 699 DI 10.2215/CJN.01600407 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 184AE UT WOS:000247612700013 ER PT J AU Dalrymple, LS Koepsell, T Sampson, J Louie, T Dominitz, JA Young, B Kestenbaum, B AF Dalrymple, Lorien S. Koepsell, Thomas Sampson, Joshua Louie, Tin Dominitz, Jason A. Young, Bessie Kestenbaum, Bryan TI Hepatitis C virus infection and the prevalence of renal insufficiency SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY NOV 08-13, 2005 CL Philadelphia, PA SP Amer Soc Nephrol ID MEMBRANOUS GLOMERULONEPHRITIS; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; ANTIVIRAL THERAPY; SERUM CREATININE; LIVER-DISEASE; BLOOD-FLOW; NEPHROPATHY; HCV; MANIFESTATIONS; GLOMERULOPATHY AB Background: Hepatitis C virus (HCV) is associated with pathologic changes in the kidney. However, the association between HCV and renal dysfunction is not well defined. Design, setting, participants, and measurements: This study estimated the prevalence of renal insufficiency among veterans who received care through the Veterans Affairs Puget Sound Health Care System. The study population consisted of veterans who underwent HCV antibody testing between January 1, 1999, and December 31, 2004, and had at least one primary care or medical subspecialty visit and at least one outpatient creatinine measurement within the 18 mo before antibody testing. Veterans were excluded when they had a history of chronic dialysis, creatinine > 5 mg/dl, or renal transplantation. Study data were extracted from the electronic medical record. Renal insufficiency was defined as a creatinine level >= 1.5 mg/dl. Multivariate logistic regression was performed to estimate the risk for renal insufficiency associated with HCV. Among 25,782 eligible veterans, 1928 were HCV antibody positive and 23,854 were HCV antibody negative. Results: Although the proportion with renal insufficiency was lower for antibody-positive versus-negative veterans (4.8 versus 6.0%), after adjustment for age, race, gender, diabetes, and hypertension, HCV-positive veterans had a 40% higher odds for renal insufficiency (odds ratio 1.40; 95% confidence interval 1.11 to 1.76) as compared with HCV-negative veterans. Conclusions: HCV was associated with an increased prevalence of renal insufficiency. C1 VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Healthcare Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Healthcare Syst, NW Hepatitis C Resource Ctr, Seattle, WA 98108 USA. VA Puget Sound Healthcare Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Nephrol, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA USA. RP Dalrymple, LS (reprint author), VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev NW Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98108 USA. EM dalrympt@u.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 NR 49 TC 42 Z9 45 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2007 VL 2 IS 4 BP 715 EP 721 DI 10.2215/CJN.00470107 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 184AE UT WOS:000247612700016 PM 17699487 ER PT J AU Gabardi, S Munz, K Ulbricht, C AF Gabardi, Steven Munz, Kristin Ulbricht, Catherine TI A review of dietary supplement-induced renal dysfunction SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID VITAMIN-C SUPPLEMENTATION; ACUTE OXALATE NEPHROPATHY; HERBAL REMEDIES; ASCORBIC-ACID; CREATINE SUPPLEMENTATION; ALTERNATIVE MEDICINE; CHROMIUM PICOLINATE; EPHEDRINE NEPHROLITHIASIS; NORDIHYDROGUAIARETIC ACID; GERMANIUM INTOXICATION AB Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education. C1 Brigham & Womens Hosp, Dept Pharm Serv, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Natl Stand & Dept Pharm Serv, Boston, MA 02114 USA. RP Gabardi, S (reprint author), Brigham & Womens Hosp, Dept Pharm Serv, Div Renal, 75 Francis St, Boston, MA 02115 USA. EM sgabardi@parbriers.org OI Gabardi, Steven/0000-0001-8022-2751 NR 97 TC 24 Z9 25 U1 4 U2 9 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2007 VL 2 IS 4 BP 757 EP 765 DI 10.2215/CJN.00500107 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 184AE UT WOS:000247612700022 PM 17699493 ER PT J AU Allen, DN Caron, JE Duke, LA Goldstein, G AF Allen, Daniel N. Caron, Joshua E. Duke, Lisa A. Goldstein, Gerald TI Sensitivity of the Halstead category test factor scores to brain damage SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID MULTIDIMENSIONAL INSTRUMENT; PRACTICAL SCALE; HEAD-INJURY; PERSEVERATION; INTELLIGENCE; SUBTESTS AB Recent factor-analytic studies of the Halstead Category Test (HCT) indicate that its seven subtests form three factors including a Counting factor (subtests I and II), a Spatial Positional Reasoning factor (subtests III, IV, and VII), and a Proportional Reasoning factor (subtests V, VI, and VII). The sensitivity and specificity of these factors to heterogeneous forms of brain damage was examined in a large sample of patients and a normal comparison sample. A prorated Impairment Index, which excluded the HCT error score, was used to assign participants with brain damage into mild, moderate, and severe impairment groups. Also, groups with various forms of neuropathology were contrasted. Results indicated that both the Spatial Positional Reasoning and the Proportional Reasoning factors were sensitive to brain damage. However, in all of the brain-damage groups, a greater percentage of errors were made on the Spatial Positional factor, suggesting that of the two it was more difficult for those with brain damage. The sensitivity and specificity of the Spatial Positional factor score for detection of brain damage was comparable to that of the total error score, which has been previously demonstrated to be an excellent indicator of brain damage. Findings provide further support for the validity of the HCT factors, and are consistent with the view that factor scores may be useful in interpreting the HCT. C1 Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Allen, DN (reprint author), Univ Nevada, Dept Psychol, 4505 Maryland Pkwy, Las Vegas, NV 89154 USA. EM daniel.allen@unlv.edu NR 33 TC 5 Z9 5 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD JUL PY 2007 VL 21 IS 4 BP 638 EP 652 DI 10.1080/13854040600744821 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 195YP UT WOS:000248448700005 PM 17613982 ER PT J AU Rosow, CE Gomery, P Chen, TY Stefanovich, P Stambler, N Israel, R AF Rosow, C. E. Gomery, P. Chen, T. Y. Stefanovich, P. Stambler, N. Israel, R. TI Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MORPHINE-INDUCED DELAY; RAT URINARY-BLADDER; CECAL TRANSIT-TIME; INHIBITION; HUMANS; ANALGESIA; RETENTION; EFFICACY AB Peripheral mechanisms may be involved in opioid actions on the urinary bladder. This double-blind study investigated whether opioid inhibition of bladder function is reversed by methyinaltrexone, a peripheral opioid antagonist. Thirteen healthy male volunteers received an intravenous (i.v.) infusion of remifentanil, 0.15 mcg/kg/min, then a single i.v. dose of study medication (methyinaltrexone 0.3 mg/kg, naloxone 0.01 mg/kg, or saline). Urodynamics were measured with indwelling bladder and rectal catheters, and pupil size was assessed with infrared pupillometry. Remifentanil decreased cletrusor pressure in 21/25 sessions and caused complete urinary retention in 18/25. Voiding was possible in 7/7, 5/12, and 0/6 sessions after naloxone, methyinaltrexone, and saline, respectively (P = 0.0013). Remifentanil caused marked miosis that was reversed by naloxone, but not methyinaltrexone or placebo (P < 0.0001). The pupil data confirm that methylnaltrexone did not reverse central opioid effects. Reversal of urinary retention by methyinaltrexone indicates that peripheral mechanisms may play a role in opioid-induced bladder dysfunction. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Progen Pharmaceut, Tarrytown, NY USA. RP Rosow, CE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM crosow@partners.org NR 22 TC 33 Z9 36 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2007 VL 82 IS 1 BP 48 EP 53 DI 10.1038/sj.clpt.6100164 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 179UU UT WOS:000247316400013 PM 17392726 ER PT J AU Laurenceau, JP Hayes, AM Feldman, GC AF Laurenceau, Jean-Philippe Hayes, Adele M. Feldman, Greg C. TI Some methodological and statistical issues in the study of change processes in psychotherapy SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review ID INDIVIDUAL-DIFFERENCES; COGNITIVE THERAPY; TEMPORAL DESIGN; DIARY METHODS; DEPRESSION; GROWTH; MODERATORS; MEDIATORS; RECOMMENDATIONS; FRAMEWORK AB As the number of psychotherapies with demonstrated efficacy accumulates, an important task is to identify principles and processes of change. This information can guide treatment refinement, integration, and future development. However, the standard randomized control trial (RCT) design can limit the questions that can be asked and the statistical analyses that can be conducted. We discuss the importance of examining the shape of change, in addition to the importance of identifying mediators and moderators of change. We suggest methodological considerations for longitudinal data collection that can improve the kinds of therapy process questions that can be examined. We also review some data analytic approaches that are being used in other areas of psychology that have the potential to capture the complexity and dynamics of change in psychotherapy. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Laurenceau, JP (reprint author), Univ Delaware, Dept Psychol, 108 Wolf Hall, Newark, DE 19716 USA. EM jlaurenceau@psych.udel.edu FU NIMH NIH HHS [L30 MH072515, K01MH64779, K01 MH064779, R21MH062662, L30 MH072515-02, R21 MH062662, K01 MH064779-01A1, R21 MH062662-01A1] NR 63 TC 93 Z9 97 U1 2 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD JUL PY 2007 VL 27 IS 6 BP 682 EP 695 DI 10.1016/j.cpr.2007.01.007 PG 14 WC Psychology, Clinical SC Psychology GA 189IY UT WOS:000247983800002 PM 17328996 ER PT J AU Hayes, AM Laurenceau, JP Feldman, G Strauss, JL Cardaciotto, L AF Hayes, Adele M. Laurenceau, Jean-Philippe Feldman, Greg Strauss, Jennifer L. Cardaciotto, LeeAnn TI Change is not always linear: The study of nonlinear and discontinuous patterns of change in psychotherapy SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; SUDDEN GAINS; POSTTRAUMATIC GROWTH; CRITICAL SESSIONS; SYMPTOM CHANGE; DEPRESSION; DISORDER; TRAUMA; LIFE; PERSONALITY AB The study of discontinuities and nonlinear change has been a fruitful endeavor across the sciences, as these shifts can provide a window into the organization of complex systems and the processes that are associated with transition. A common assumption in psychotherapy research has been that change is gradual and linear. The research designs and statistics used to study change often reflect this assumption, but some recent research reveals other patterns of change. We briefly review relevant literature on dynamical systems theory and on life transition and post-traumatic growth to highlight the significance of nonlinear and discontinuous change across areas of psychology. We describe recent applications of these ideas and methods to the study of change in psychotherapy and encourage their use to complement more traditional clinical trial designs. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Durham VA, Durham, NC USA. RP Hayes, AM (reprint author), Univ Delaware, Dept Psychol, 108 Wolf Hall, Newark, DE 19716 USA. EM ahayes@psych.udel.edu FU NIMH NIH HHS [K01MH64779, R21 MH062662-04, K01 MH064779, R21MH062662, R21 MH062662] NR 69 TC 119 Z9 124 U1 7 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD JUL PY 2007 VL 27 IS 6 BP 715 EP 723 DI 10.1016/j.cpr.2007.01.008 PG 9 WC Psychology, Clinical SC Psychology GA 189IY UT WOS:000247983800004 PM 17316941 ER PT J AU Fessler, HE Derdak, S Ferguson, ND Hager, DN Kacmarek, RM Thompson, T Brower, RG AF Fessler, Henry E. Derdak, Stephen Ferguson, Niall D. Hager, David N. Kacmarek, Robert M. Thompson, Taylor Brower, Roy G. TI A protocol for high-frequency oscillatory ventilation in adults: Results from a roundtable discussion SO CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; high-frequency ventilation; protocols; acute respiratory distress syndrome; acute lung injury; ventilator-associated lung injury; acute respiratory failure ID RESPIRATORY-DISTRESS-SYNDROME; CONVENTIONAL MECHANICAL VENTILATION; EXPIRATORY PRESSURE TRIAL; CHRONIC LUNG-DISEASE; RECRUITMENT MANEUVERS; TIDAL VOLUME; GAS-EXCHANGE; INJURY; MODEL; STRATEGY AB Objective: Ventilator settings typically used for high-frequency oscillatory ventilation (HFO) in adults provide acceptable gas exchange but may not take best advantage of its lung-protective aspects. We provide guidelines for HFO in adults with acute respiratory distress syndrome that should optimize the lung-protective characteristics of this ventilation mode. Design: Roundtable discussions, iterative revisions, and consensus. Setting: Five academic medical centers. Patients: Not applicable. Interventions: Participants addressed how to best maintain ventilation through combinations of oscillation pressure amplitude, frequency, and the use of an endotracheal tube cuff leak, and to maintain oxygenation through combinations of recruitment maneuvers, mean airway pressure, and oxygen concentration. The guiding principles were to provide lung protective ventilation by minimizing the size of tidal volumes, and balance the risks and benefits of lung recruitment and distension. Main Results: HFO may provide smaller tidal volumes and more complete lung recruitment than conventional modes. To optimize these features, we recommend use of the maximum pressure-oscillation amplitude coupled with the highest tolerated frequency, targeting a pH of only 7.25-7.35. This will yield a smaller tidal volume than typical HFO settings where frequency is limited to 6 Hz or less and pressure amplitude is submaximal. Lung recruitment can be achieved with the use of recruitment maneuvers, especially during the first several days of HFO. Recruitment may be augmented or sustained with generous mean airway pressures. These may either be chosen from a table of recommended mean airway pressure and oxygen concentration combinations, or individually titrated based on the oxygenation response of each patient. Conclusions: Modification of the goals and tactics of HFO use may better protect against ventilator-associated lung injury. Further clinical trials are needed to compare the effects on patient outcome of the best use of HFO compared to the most protective use of conventional modes in adult acute respiratory distress syndrome. C1 Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. Wilford Hall USAF Med Ctr, San Antonio, TX USA. Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Resp Care, Div Pulm & Crit Care Med, Boston, MA 02114 USA. RP Fessler, HE (reprint author), Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. EM hfessler@jhmi.edu OI Ferguson, Niall/0000-0002-6213-5264 FU NHLBI NIH HHS [HL 073994-01] NR 32 TC 68 Z9 70 U1 1 U2 2 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 JUL PY 2007 VL 35 IS 7 BP 1649 EP 1654 DI 10.1097/01.CCM.0000269026.40739.2E PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 181GB UT WOS:000247424100003 PM 17522576 ER PT J AU Doria, A Abumrad, NA AF Doria, Alessandro Abumrad, Nada A. TI Why type 2 diabetes is not an equal opportunity disease: recent progress in genetics SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Editorial Material C1 [Abumrad, Nada A.] Washington Univ, Div Nutr Sci, Dept Med & Cell Biol & Phys, Dept Med, St Louis, MO 63110 USA. [Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Abumrad, NA (reprint author), Washington Univ, Div Nutr Sci, Dept Med & Cell Biol & Phys, Dept Med, 660 S Euclid Ave, St Louis, MO 63110 USA. EM nabumrad@im.wustl.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JUL PY 2007 VL 10 IS 4 BP 389 EP 390 DI 10.1097/MCO.0b013e32821c6174 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 318HG UT WOS:000257081600001 ER PT J AU Florez, JC AF Florez, Jose C. TI The new type 2 diabetes gene TCF7L2 SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE genetic association; single nucleotide polymorphisms; TCF7L2; type 2 diabetes ID SUSCEPTIBILITY GENE; INSULIN-RESISTANCE; COMMON VARIANTS; TYPE-2; ASSOCIATION; RISK; POPULATION; POLYMORPHISMS; GLUCOSE; METAANALYSIS AB Purpose of review Common variants in the gene that encodes the transcription factor 7-like 2 (TCF7L2) have been strongly associated with type 2 diabetes. This highly reproducible association may uncover novel mechanisms of glycemic pathophysiology. Recent findings The initial publications of an association of common variants in TCF7L2 with type 2 diabetes in people of European descent has been followed by an avalanche of replication reports. These papers not only confirm the original finding, but also extend it to other populations, fine map the source of the association signal, describe its effect on metabolic parameters in humans, open the door to a more precise molecular characterization, and provide an insigiht into its possible impact on diabetes therapy. Summary The discovery of TCF7L2 as a diabetes gene illustrates that novel true diabetes genes can be found, their association with type 2 diabetes replicated and their effect incorprated into risk prediction models. It is hoped that the detection of other such genes in genome-wide association scans will help elucidate the genetic architecture of this disease. C1 [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] MIT, Cambridge, MA 02139 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Simches Res Bldg,CPZN 6820, Boston, MA 02114 USA. EM jcflorez@partners.org FU NIDDK NIH HHS [1 K23 DK65978-03] NR 37 TC 69 Z9 71 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JUL PY 2007 VL 10 IS 4 BP 391 EP 396 DI 10.1097/MCO.0b013e3281e2c9be PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 318HG UT WOS:000257081600002 PM 17563454 ER PT J AU Triant, VA Grinspoon, SK AF Triant, Virginia A. Grinspoon, Steven K. TI Vascular dysfunction and cardiovascular complications SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE cardiovascular; endothelial dysfunction; HIV; myocardial infarction AB Purpose of review Antiretroviral (ARV) therapy has altered the course of HIV disease and dramatically increased the lifespan of HIV-infected individuals. Accumulating evidence, however, suggests that prolonged ARV use contributes to metabolic and cardiovascular changes. Understanding the toxicities of ARV treatment and sequelae of long-term infection is critical. This review will examine recent evidence related to vascular dysfunction and cardiovascular complications in HIV infection. Recent findings Recent studies investigating circulating markers of inflammation, surrogate markers of subclinical atherosclerotic disease, and novel imaging modalities suggest the presence of endothelial dysfunction in HIV-infected patients. In addition, data from several recently updated cohort studies confirm an association between ARV therapy and cardiovascular events. Summary New data suggest that cardiovascular disease is increased among HIV-infected patients receiving highly active ARV therapy. The mechanisms of increased cardiovascular disease may relate to direct effects of the HIV virus and inflammation on the vasculature or to toxicities from specific ARV therapies, which may increase traditional cardiovascular risk factors. Understanding and modifying these risks and preventing cardiovascular events are critical to the long-term management of the HIV-infected patient. C1 [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Brigham & Womens Hosp, Boston, MA 02114 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Brigham & Womens Hosp, 55 Fruit St,Longfellow 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIAID NIH HHS [T32 AI007387] NR 52 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JUL PY 2007 VL 2 IS 4 BP 299 EP 304 DI 10.1097/COH.0b013e3281e7e831 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NU UT WOS:000208417900008 PM 19372902 ER PT J AU Ansel, KM Thai, TH Kanellopoulou, C Muljo, SA Lapan, AD Monticelli, S Heissmeyer, VH Rajewsky, K Rao, A AF Ansel, K. Mark Thai, To-Ha Kanellopoulou, Chryssa Muljo, Stefan A. Lapan, Ariya D. Monticelli, Silvia Heissmeyer, Vigo H. Rajewsky, Klaus Rao, Anjana TI Endogenous RNA interference influences cytokine gene expression SO CYTOKINE LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Cytokine-Society CY OCT 26-30, 2007 CL San Francisco, CA SP Int Cytokine Soc C1 [Ansel, K. Mark; Muljo, Stefan A.; Lapan, Ariya D.; Heissmeyer, Vigo H.; Rajewsky, Klaus; Rao, Anjana] CBR Inst Biomed Res, Boston, MA USA. [Ansel, K. Mark] Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Thai, To-Ha; Muljo, Stefan A.; Rajewsky, Klaus; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kanellopoulou, Chryssa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Monticelli, Silvia] Biomed Res Inst, Bellinzona, Switzerland. [Heissmeyer, Vigo H.] GSF Natl Res Ctr Environm & Hlth, Inst Mol Immunol, Munich, Bavaria, Germany. RI Muljo, Stefan/F-5671-2015 OI Muljo, Stefan/0000-0003-1013-446X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL PY 2007 VL 39 IS 1 MA 6 BP 2 EP 2 DI 10.1016/j.cyto.2007.07.011 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 224BV UT WOS:000250421500007 ER PT J AU Chen, Q Vardam, T Fisher, D Wang, WC Rose-John, S Ernst, M Von Andrian, U Baumann, H Evans, SS AF Chen, Qing Vardam, Trupti Fisher, Daniel Wang, Wan-Chao Rose-John, Stefan Ernst, Matthias Von Andrian, Ulrich Baumann, Heinz Evans, Sharon S. TI Central role of the lymphocyte-endothelial-interleukin-6 axis in promoting lymphocyte trafficking during fever-range thermal stress SO CYTOKINE LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Cytokine-Society CY OCT 26-30, 2007 CL San Francisco, CA SP Int Cytokine Soc C1 [Chen, Qing; Vardam, Trupti; Fisher, Daniel; Wang, Wan-Chao; Evans, Sharon S.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY USA. [Rose-John, Stefan] Univ Kiel, Dept Biochem, Kiel, Germany. [Ernst, Matthias] Harvard Univ, Sch Med, CBR, Biomed Res Inst,Dept Pathol, Boston, MA USA. [Von Andrian, Ulrich] Ludwig Inst Canc Res, Colon Mol & Cell Biol Lab, Melbourne, Vic, Australia. [Baumann, Heinz] Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY USA. RI Rose-John, Stefan/A-7998-2010; Ernst, Matthias/D-5111-2012 OI Rose-John, Stefan/0000-0002-7519-3279; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL PY 2007 VL 39 IS 1 MA 19 BP 6 EP 6 DI 10.1016/j.cyto.2007.07.024 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 224BV UT WOS:000250421500020 ER PT J AU Rosenbach, M Werth, VP AF Rosenbach, M. Werth, Victoria P. TI Dermatologic therapeutics: thalidomide. A practical guide SO DERMATOLOGIC THERAPY LA English DT Review DE dermatologic use; dermatology; guidelines; thalidomide ID VERSUS-HOST DISEASE; NECROSIS-FACTOR-ALPHA; GIANT MUCOCUTANEOUS APHTHAE; DOUBLE-BLIND TRIAL; TNF-ALPHA; PYODERMA-GANGRENOSUM; ERYTHEMA MULTIFORME; BEHCETS-DISEASE; LEPRA REACTIONS; POTENTIAL USES AB Thalidomide was first introduced in the 1950s, and its widespread use led to thousands of birth defects through the 1960s; it was quickly withdrawn from the market. A fortuitous discovery identified during treatment of patients with erythema nodosum leprosum led to the recognition of the potent anti-inflammatory effects of thalidomide and a resurgence of interest in the drug. In the ensuing decades, thalidomide has been recognized as a potential treatment option in a number of dermatologic conditions. This article reviews the history, pharmacology, mechanisms of action, and off-label uses of thalidomide and serves as a guide for dermatologists to comfortably and safely institute and monitor thalidomide to patients with cutaneous disease. C1 Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19119 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, 2 Rhodes Pavilion,3600 Spruce St, Philadelphia, PA 19119 USA. EM werth@mail.med.upenn.edu NR 100 TC 12 Z9 12 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD JUL-AUG PY 2007 VL 20 IS 4 BP 175 EP 186 DI 10.1111/j.1529-8019.2007.00132.x PG 12 WC Dermatology SC Dermatology GA 225DL UT WOS:000250497200003 PM 17970884 ER PT J AU Fujino, A Pieretti-Vanmarcke, R Wong, A Donahoe, PK Arango, NA AF Fujino, Akihiro Pieretti-Vanmarcke, Rafael Wong, Anita Donahoe, Patricia K. Arango, Nelson A. TI Sexual dimorphism of G-protein subunit Gng13 expression in the cortical region of the developing mouse ovary SO DEVELOPMENTAL DYNAMICS LA English DT Article DE ovary development; G-proteins; gene expression ID FEMALE MICE; DIFFERENTIATION; GENE; SRY; SPERMATOGENESIS; G-GAMMA-13; CHROMOSOME; CELLS; WNT4 AB In our search for genes required for the development and function of mouse gonads, we identified Gng13 (guanine nucleotide binding protein 13, gamma), a gene with an embryonic expression pattern highly restricted to the ovary. Based on reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, Gng13 is expressed in both XX and XY gonads at embryonic day (E) 11.5, but becomes up-regulated in the XX gonad by E12.5. Expression is retained after treatment with busulfan, a chemical known to eliminate germ cells, pointing to the soma as a site of Gng13 transcription. In situ hybridization of embryonic ovarian tissue sections further localized the expression to the cortex of the developing XX gonad. Gng13 expression in the adult is also highly restricted. Northern blot analyses and Genomic Institute of the Novartis Research Foundation expression profiling of adult tissues detected very high expression in the cerebrum and cerebellum, in addition to, a weaker signal in the ovary. Gng13 belongs to a well-known family of signal transduction molecules with functions in many aspects of development and organ physiology. Here, we report that, in the developing mouse embryo, expression of Gng13 mRNA is highly restricted to the cortex of the XX gonad during sexual differentiation, suggesting a role for this gene during ovarian development. Developmental Dynamics 236:1991-1996, 2007. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Arango, NA (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, MCPZN6212,185 Cambridge St, Boston, MA 02114 USA. EM arango@helix.mgh.harvard.edu FU NICHD NIH HHS [F32HD43539, HD32212] NR 25 TC 4 Z9 4 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 JUL PY 2007 VL 236 IS 7 BP 1991 EP 1996 DI 10.1002/dvdy.21183 PG 6 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 190EO UT WOS:000248041000025 PM 17497668 ER PT J AU Dedkov, EI Thomas, MT Sonka, M Yang, F Chittenden, TW Rhodes, JM Simons, M Ritman, EL Tomanek, RJ AF Dedkov, Eduard I. Thomas, Mathew T. Sonka, Milan Yang, Fuxing Chittenden, Thomas W. Rhodes, John M. Simons, Michael Ritman, Erik L. Tomanek, Robert J. TI Synectin/Syndecan-4 regulate coronary arteriolar growth during development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE synectin/syndecan-4; coronary arteriolar growth; mice; arteriogenesis ID INTRATHORACIC AIRWAY TREES; CYTOPLASMIC DOMAIN; CELL-MIGRATION; IN-VIVO; SYNDECAN-4; ANGIOGENESIS; ESTROGEN; SYNECTIN; RECEPTOR; PROTEIN AB Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin(-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 mu m) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin. C1 New York Coll Osteopath Med, Dept Biomed Sci, Old Westbury, NY USA. Harvard Sch Publ Hlth, Dana Farber Canc Inst, Funct Genom & Computat Biol Grp, Boston, MA USA. Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA. Dartmouth Coll Sch Med, Angiogenesis Res Ctr, Dept Med, Hanover, NH USA. Dartmouth Coll Sch Med, Angiogenesis Res Ctr, Dept Pharmacol, Hanover, NH USA. Dartmouth Coll Sch Med, Angiogenesis Res Ctr, Dept Toxicol, Hanover, NH USA. Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA. RP Tomanek, RJ (reprint author), Univ Iowa, Dept Anat & Cell Biol, 1-402 BSB, Iowa City, IA 52242 USA. EM robert-tomanek@uiowa.edu RI Simons, Michael/G-8553-2014; OI Simons, Michael/0000-0003-0348-7734; Dedkov, Eduard/0000-0002-7309-7662 FU NHLBI NIH HHS [HL62289, HL53793, R01 HL075446]; NIBIB NIH HHS [EB000305] NR 33 TC 19 Z9 19 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUL PY 2007 VL 236 IS 7 BP 2004 EP 2010 DI 10.1002/dvdy.21201 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 190EO UT WOS:000248041000027 PM 17576142 ER PT J AU Yatoh, S Dodge, R Akashi, T Omer, A Sharma, A Weir, GC Bonner-Weir, S AF Yatoh, Shigeru Dodge, Rikke Akashi, Tomoyuki Omer, Abdulkadir Sharma, Arun Weir, Gordon C. Bonner-Weir, Susan TI Differentiation of affinity-purified human pancreatic duct cells to beta-cells SO DIABETES LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; INSULIN-SECRETING CELLS; ADULT HUMAN PANCREAS; IN-VITRO; PROGENITOR CELLS; PRECURSOR CELLS; MOUSE PANCREAS; GROWTH-FACTOR; HUMAN ISLETS; ENDOCRINE AB To test whether pancreatic duct cells are in vitro progenitors, they were purified from dispersed islet-depleted human pancreatic tissue using CA19-9 antibody. The purified fraction was almost entirely CK19(+) with no insulin(+) cells, whereas the unpurified cells (crude duct) were 56% CK19(+) and 0.4% insulin(+) of total cells (0.7% of CK19(+) cells). These cells were expanded as monolayers, aggregated under serum-free conditions, and transplanted into normoglycemic NOD/SCID mice. In crude duct grafts, insulin(+) cells increased to 6.1% of CK19(+) cells. Purified duct cells had slow expansion and poor aggregation, as well as engraftment. The addition of 0.1% cultured stromal cells improved these parameters. These stromal cells contained no CK19(+), cells and no insulin by either quantitative RT-PCR or immunohistochemistry; stromal cell aggregates and grafts contained no insulin(+) cells. Aggregation of purified duct plus stromal preparations induced insulin(+) cells (0.1% of CK19+ cells), with further increase to 1.1% in grafts. Insulin mRNA mirrored these changes. In these grafts, all insulin(+) cells were in duct-like structures, while in crude duct grafts, 85% were. Some insulin(+) cells coexpressed duct markers (CK19 and CA19-9) and heat shock protein (HSP)27, a marker of nonislet cells, suggesting the transition from duct. Thus, purified duct cells from adult human pancreas can differentiate to insulin-producing cells. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu FU NCRR NIH HHS [U42 RR16606]; NIDDK NIH HHS [DK44523, DK74879, P30 DK36836-16] NR 35 TC 94 Z9 100 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2007 VL 56 IS 7 BP 1802 EP 1809 DI 10.2337/db06-1670 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186GV UT WOS:000247768000006 PM 17473224 ER PT J AU Lachin, JM Genuth, S Nathan, DM Rutledge, BN AF Lachin, John M. Genuth, Saul Nathan, David M. Rutledge, Brandy N. TI The hemoglobin glycation index is not an independent predictor of the risk of microvascular complications in the diabetes control and complications trial SO DIABETES LA English DT Article ID BIOLOGICAL VARIATION; GLYCOSYLATED HEMOGLOBIN; NEPHROPATHY; RETINOPATHY; HBA(1C); PROGRESSION; FRUCTOSAMINE; VARIABILITY; DEGLYCATION; GLYCEMIA AB The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy aimed at improved glucose control markedly reduced the risk of diabetes complications compared with conventional therapy. The principal determinant of risk was the history of glycemia. Recently, McCarter et al. (Diabetes Care 27:1259-1264, 2004) have presented analyses of the publicly available DCCT data using their hemoglobin glycation index (HGI), which is computed as the difference between the observed HbA1c (AIC) and that predicted from the level of blood glucose. In their analyses, the HGI level was a significant predictor of progression of retinopathy and nephropathy in the DCCT, which the authors claimed to support the hypothesis that the biological propensity for glycation, so-called biological variation in glycation, is another mechanism that determines risk of complications. However, we have criticized these analyses and conclusions because, from statistical principles, the glycation index must be positively correlated with the AIC level and thus may simply be a surrogate for A1C. Herein, we present the statistical properties of the glycation index to document its high correlation with AIC. We then replicate the analyses of McCarter et al. using both the HGI and the A1C together. Analyses show conclusively that the glycation index is not an independent risk factor for microvascular complications and that the effect of the glycation index on risk is wholly explained by the associated level of A1C. The HGI should not be used to estimate risk of complications or to guide therapy. C1 George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd, Rockville, MD 20852 USA. EM jml@biostat.bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841 NR 24 TC 30 Z9 31 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2007 VL 56 IS 7 BP 1913 EP 1921 DI 10.2337/db07-0028 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186GV UT WOS:000247768000020 PM 17360979 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, Monca M. Demissie, Kitaw Lu, Shou-En Pogach, Leonard M. TI Impact of oral antihyperglycemic therapy on all-cause mortality among patients with diabetes in the Veterans Health Administration SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE CONTROL; PROPENSITY SCORES; METFORMIN; AFFAIRS; SULFONYLUREAS; COMPLICATIONS; INFERENCE; DISEASE; RISK AB OBJECTIVE - The objective of this analysis was to evaluate the impact of several classes of oral antihyperglycemic therapy relative to sulfonylurea monotherapy on all-cause mortality among a cohort of patients with diabetes from the Veterans Health Administration (VHA). RESEARCH DESIGN AND METHODS - A retrospective cohort study using data obtained from the VHA Diabetes Epidemiology Cohort was used. Users of oral antihyperglycemic therapy were classified into the following cohorts: sulfonylurea monotherapy, metformin monotherapy, metformin plus sulfonylurea, thiazolidinedione (TZD) use alone or in combination with other oral agents (TZD users), and no drug therapy. All-cause mortality was the outcome of interest. Multivariate mixed models incorporating a propensity score to account for imbalance among cohorts were used to estimate drug effects on mortality with associated 95% ClS. RESULTS - A total of 39,721 patients with diabetes were included in the study. Adjusted odds ratios and 95% ClS for all-cause mortality were 0.87 (0.68-1.10) for metformin monotherapy users, 0.92 (0.82-1.05) for metformin plus sulfonylurea users, and 1.04 (0.75-1.46) for TZD users, relative to sulfonylurea monotherapy users. CONCLUSIONS - We did not find any significant drug effect on all-cause mortality for any oral treatment cohorts relative to sulfonylurea oral monotherapy. C1 VA New Jersey Hlth Care Syst, Ctr Hlth Care knowledge & Management, E Orange, NJ USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Piscataway, NJ 08854 USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. RP Kahler, KH (reprint author), Nova Pharmaceut Corp, 1 Hlth Plaza,Room 405-3117, E Hanover, NJ 07936 USA. EM kristijan.kahler@novartis.com NR 23 TC 30 Z9 32 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 JUL PY 2007 VL 30 IS 7 BP 1689 EP 1693 DI 10.2337/dc06-2272 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186GZ UT WOS:000247768400001 PM 17440170 ER PT J AU Hood, KK Butler, DA Anderson, BJ Laffel, LMB AF Hood, Korey K. Butler, Deborah A. Anderson, Barbara J. Laffel, Lori M. B. TI Updated and revised Diabetes Family Conflict Scale SO DIABETES CARE LA English DT Article ID QUALITY-OF-LIFE; GLYCEMIC CONTROL; METABOLIC-CONTROL; INTENSIVE TREATMENT; ADOLESCENTS; MELLITUS; CHILDREN; YOUTH; MANAGEMENT; ADHERENCE AB OBJECTIVE - The purpose of this study was to update the Diabetes Family Conflict Scale (DFCS) in the era of intensive diabetes management and provide an indication of its psychometric properties. RESEARCH DESIGN AND METHODS - The revised DFCS and measures of negative emotions around blood glucose monitoring (BGM), quality of life, and perceived parental burden from diabetes management were completed by 202 children and adolescents with type I diabetes and their primary caregivers. Insulin regimen, adherence, and glycemic control were also assessed. RESULTS - The revised DFCS demonstrated strong psychometric properties. There was acceptable internal consistency for child and caregiver forms of the DFCS. Factor analysis revealed two factors related to direct and indirect management tasks. Both child (r = 0.27, P < 0.01) and caregiver (r = 0.26, P < 0.01) DFCS scores were correlated with A1C values. Multivariate analysis of factors usually associated with A1C values showed an additive, independent contribution of diabetes-specific family conflict to the prediction of glycemic control: F (12,189) = 6.17, P < 0.01, R-2 = 0.28. Conflict around direct management tasks (e.g., BGM) was a more important predictor of higher A1C levels than conflict around indirect management tasks (e.g., telling friends about diabetes). CONCLUSIONS - The revised and updated DFCS demonstrates strong psychometric properties and can be used as a tool for measuring the level of diabetes-specific conflict in families with children and adolescents with type 1 diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect,Genet & Epid, Boston, MA 02215 USA. Texas Childrens Hosp, Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. RP Laffel, LMB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect,Genet & Epid, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [DK-46887, K23 DK-073340, K23 DK073340, K23 DK073340-02, R01 DK046887] NR 28 TC 84 Z9 84 U1 4 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2007 VL 30 IS 7 BP 1764 EP 1769 DI 10.2337/dc06-2358 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186GZ UT WOS:000247768400014 PM 17372149 ER PT J AU Haas, L AF Haas, Linda TI Psychological insulin resistance - Scope of the problem SO DIABETES EDUCATOR LA English DT Article ID THERAPY; ASSOCIATION; CARE C1 Seattle Div, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Haas, L (reprint author), Seattle Div, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM linda.haas@va.gov NR 9 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JUL-AUG PY 2007 VL 33 SU 7 BP 228S EP 231S DI 10.1177/0145721707305694 PG 4 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 203YF UT WOS:000249009200001 PM 17656738 ER PT J AU Haas, L AF Haas, Linda TI Provider psychological insulin resistance - Easing the transition SO DIABETES EDUCATOR LA English DT Article ID GLYCEMIC CONTROL; BASAL INSULIN; THERAPY; GLARGINE; INITIATION C1 Seattle Div, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Haas, L (reprint author), Seattle Div, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM linda.haas@va.gov NR 12 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JUL-AUG PY 2007 VL 33 SU 7 BP 245S EP 247S DI 10.1177/0145721707305702 PG 3 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 203YF UT WOS:000249009200004 PM 17656741 ER PT J AU Haas, L Polonsky, W AF Haas, Linda Polonsky, William TI The tipping point - Overcoming barriers SO DIABETES EDUCATOR LA English DT Article ID BASAL INSULIN; THERAPY C1 Seattle Div, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Haas, L (reprint author), Seattle Div, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM linda.haas@va.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JUL-AUG PY 2007 VL 33 SU 7 BP 248S EP 250S DI 10.1177/0145721707305703 PG 3 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 203YF UT WOS:000249009200005 PM 17656742 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 DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE sclerosing polycystic adenosis; salivary gland; fine-needle aspiration biopsy; cytology ID PAPILLARY-CYSTIC VARIANT; ACINIC-CELL-CARCINOMA; SALIVARY-GLAND; FEATURES AB Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary gland analogous to fibrocystic disease of the breast. Recognition of this benign entity is important since the differential diagnosis includes other more common benign and malignant salivary gland neoplasms, particularly mucoepidermoid carcinoma and tumors with cystic and oncocytic features. While the histomorphology of SPA is well documented, there is only one other cytologic description of SPA in the English-language literature. Here we describe the fine-needle aspiration biopsy findings in a case of SPA of the parotid gland in an 84-year-old woman. The aspirate was characterized by flat cohesive sheets of epithelial cells with moderate amounts Of finely granular oncocytic cytoplasm and enlarged round nuclei with indistinct nucleoli. Some epithelial groups formed glandular structures with lumens, and the background contained small amounts of delicate mucoproteinaceous material. Occasional markedly vacuolated cells were present as well as many cells with apocrine change manifested by well-defined apical snouting. Familiarity with the cytomorphologic features of SPA, including its characteristic apocrine changes, is important for distinguishing it from other more clinically significant salivary gland lesions. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cambridge Hlth Alliance, Cambridge, England. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org NR 13 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUL PY 2007 VL 35 IS 7 BP 444 EP 447 DI 10.1002/dc.20671 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 184VL UT WOS:000247670600013 PM 17580340 ER PT J AU Humbert, IA Robbins, J AF Humbert, Ianessa A. Robbins, JoAnne TI Normal swallowing and functional magnetic resonance imaging: A systematic review SO DYSPHAGIA LA English DT Review DE deglutition; deglutition disorders; functional magnetic resonance imaging ID TRAUMATIC BRAIN-INJURY; CEREBRAL CORTICAL REPRESENTATION; DYSPHAGIA FOLLOWING STROKE; EVENT-RELATED FMRI; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; TONGUE MOVEMENT; ASPIRATION PNEUMONIA; MEDULLARY INFARCTION; HEMISPHERIC STROKE AB Unknowns about the neurophysiology of normal and disordered swallowing have stimulated exciting and important research questions. Previously, these questions were answered using clinical and animal studies. However, recent technologic advances have moved brain-imaging techniques such as functional magnetic resonance imaging (fMRI) to the forefront of swallowing neurophysiology research. This systematic review has summarized the methods and results of studies of swallowing neurophysiology of healthy adults using fMRI. A comprehensive electronic and hand search for original research was conducted, including few search limitations to yield the maximum possible number of relevant Studies. The participants, study design, tasks, and brain image acquisition were reviewed and the results indicate that the primary motor and sensory areas were most consistently active in the healthy adult participants across the relevant studies. Other prevalent areas of activation included the anterior cingulate cortex and insular cortex. Review limitations and suggested future directions are also discussed. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Med, Madison, WI 53705 USA. RP Humbert, IA (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Med, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM humbert@wise.edu FU NCRR NIH HHS [8K12RR023268-02, K12 RR023268-02, K12 RR023268]; NIDCD NIH HHS [L30 DC008513-01, L30 DC008513] NR 68 TC 35 Z9 39 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD JUL PY 2007 VL 22 IS 3 BP 266 EP 275 DI 10.1007/s00455-007-9080-9 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 187TY UT WOS:000247872600012 PM 17440775 ER PT J AU Jassal, DS Neilan, TG Picard, MH Wood, MJ AF Jassal, Davinder S. Neilan, Tomas G. Picard, Michael H. Wood, Malissa J. TI Stress echocardiography: Abnormal response of tissue doppler-derived indices to dobutamine in the absence of obstructive coronary artery disease in patients with chronic renal failure SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE diastolic dysfunction; stress echocardiography; renal disease ID REGIONAL DIASTOLIC FUNCTION; SENSITIVE INDICATOR; FILLING PRESSURES; VELOCITY; RELAXATION AB Background: Abnormal tissue Doppler (TD)-derived indices during dobutamine stress echocardiography (DSE) can predict the presence of coronary artery disease (CAD) in patients with normal renal function. These indices include a reduction in annular systolic velocity (S'), a decrease in early diastolic annular velocity (E'), and prolongation of the time to E'. However, the ability of these indices to detect or exclude CAD in patients with chronic renal failure (CRF) is unclear. Objective: To examine the ability of TD-derived indices to detect or exclude the presence of CAD in patients with CRF. Methods: We evaluated a total of 30 patients (13 males, mean age 57 +/- 15 years) using both DSE and coronary angiography. This cohort consisted of 12 control patients with normal renal function (mean creatinine 0.5 mg/dL) and 18 patient with CRF (mean creatinine 2.5 mg/dL). At each stage of the DSE, left ventricular (LV) diastolic function was assessed using conventional (peak early (E) and late (A) transmitral, E/A ratio, E-wave deceleration time (DT), and isovolumic relaxation time (IVRT)) and TD-derived indices (lateral annular systolic (S'), early diastolic (E'), and late atrial velocities (A'), time to E' and E/E'). Results: All 30 patients had a normal DSE based on systolic regional function and a normal coronary angiogram. There was no difference in E, A, E/A, DT or IVRT between the two groups at each stage. Despite normal coronaries, patients with CRF demonstrated lower S' and E' velocities at peak stress compared to the control patients (8.0 +/- 2.2 cm/sec vs 15.1 +/- 2.6, P < 0.05 and 6.7 +/- 1.6 cm/sec vs 13.3 +/- 3.1, P < 0.05, respectively). During DSE, the time to E' at peak stress in CRF patients was also prolonged compared to control (400 +/- 44 ms vs 329 +/- 51, P < 0.05). Patients with CRF also had increased filling pressures (as estimated by E/E') as compared to controls at peak stress (14.7 +/- 5.2 vs 7.4 +/- 1.5, P < 0.05, respectively). Conclusion: In patients with CRF, a reduction in TD derived indices does not predict the presence of obstructive CAD. C1 St Boniface Gen Hosp, Bergen Cardiac Care Ctr, Div Cardiol, Dept Cardiac Sci,Inst Cardiovasc Sci, Winnipeg, MB R2H 2A6, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02115 USA. RP Jassal, DS (reprint author), St Boniface Gen Hosp, Bergen Cardiac Care Ctr, Div Cardiol, Dept Cardiac Sci,Inst Cardiovasc Sci, Rm Y3010,409 Tache Ave, Winnipeg, MB R2H 2A6, Canada. EM djassal@sbgh.mb.ca OI Picard, Michael/0000-0002-9264-3243 NR 26 TC 7 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JUL PY 2007 VL 24 IS 6 BP 580 EP 586 DI 10.1111/j.1540-8175.2007.00455.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 180WR UT WOS:000247398500004 PM 17584197 ER PT J AU Ramaswamy, S Seminara, SB Pohl, CR DiPietro, MJ Crowley, WF Plant, TM AF Ramaswamy, Suresh Seminara, Stephanie B. Pohl, Clifford R. DiPietro, Meloni J. Crowley, William F., Jr. Plant, Tony M. TI Effect of continuous intravenous administration of human metastin 45-54 on the neuroendocrine activity of the hypothalamic-pituitary-testicular axis in the adult male rhesus monkey (Macaca mulatta) SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat ID GONADOTROPIN-RELEASING-HORMONE; PROTEIN-COUPLED RECEPTOR; METASTASIS-SUPPRESSOR GENE; KISS-1; KISSPEPTIN; GPR54; TESTOSTERONE; REPRODUCTION; ACTIVATION; SECRETION AB In agonadal juvenile male monkeys, continuous administration of human metastin 45 - 54 (hu metastin 45 - 54) leads to desensitization of its receptor, G protein-coupled receptor 54 (GPR54), and decreased LH. The present study extended this observation to the adult male monkey, a more preclinically relevant model in which robust activity in the hypothalamic-pituitary-testicular axis is present. Continuous iv infusion of hu metastin 45 - 54 at either 200 or 400 mu g/h elicited a marked rise in circulating LH that peaked 2 - 3 h after initiation of treatment. Thereafter, levels declined, and by 24 h, LH in metastin 45-54-infused animals was similar to control. LH release in response to an iv bolus of hu metastin 45 - 54 ( 10 - 30 mu g) during the final 3 h of continuous infusion was truncated or abolished ( low and high peptide dose, respectively). GPR54 desensitization by the high-dose metastin 45 - 54 infusion was associated with compromised pituitary response to a bolus GnRH injection (0.3 mu g). LH pulse amplitude and pulse frequency were markedly suppressed during high-dose metastin 45 - 54 treatment. Surprisingly, the fidelity of the relationship between circulating testosterone ( T) and LH was distorted during the high-dose peptide infusion. Thus, for a given concentration of LH, T levels were invariably higher during the high-dose metastin 45 - 54 infusion than during vehicle, suggesting that the peptide may exert direct actions on the testis to amplify T production. These findings support the notion that GPR54 is desensitized by continuous exposure to ligand, and they raise the possibility of an intratesticular role of GPR54. C1 Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. Harvard Univ, Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Massachusetts Gen Hosp,Dept Med, Boston, MA 02114 USA. Duquesne Univ, Sch Hlth Sci, Dept Phys Therapy, Pittsburgh, PA 15282 USA. RP Plant, TM (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. EM plant1@pitt.edu FU NICHD NIH HHS [U54 HD 08610, U54 HD 28138, R01 HD 13254, U54 HD028138, U54 HD029164] NR 23 TC 86 Z9 87 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2007 VL 148 IS 7 BP 3364 EP 3370 DI 10.1210/en.2007-0207 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179PN UT WOS:000247302300039 PM 17412800 ER PT J AU Chen, Y Aguirre, AD Hsiung, PL Desai, S Herz, PR Pedrosa, M Huang, Q Figueiredo, M Huang, SW Koski, A Schmitt, JM Fujimoto, JG Mashimo, H AF Chen, Y. Aguirre, A. D. Hsiung, P.-L. Desai, S. Herz, P. R. Pedrosa, M. Huang, Q. Figueiredo, M. Huang, S.-W. Koski, A. Schmitt, J. M. Fujimoto, J. G. Mashimo, H. TI Ultrahigh resolution optical coherence tomography of Barrett's esophagus: preliminary descriptive clinical study correlating images with histology SO ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc ID HIGH-GRADE DYSPLASIA; GASTROINTESTINAL-TRACT; GI TRACT; BIOPSY; ADENOCARCINOMA AB Background and study aims: Endoscopic ultrahigh resolution optical coherence tomography (UHR OCT) achieves an axial image resolution of similar to 5 pm, which is 2 - 3 times finer than standard endoscopic OCT imaging. This study investigated the capability of endoscopic UHR OCT for imaging patients with Barrett's esophagus. Patients and methods: Fivty volunteers previously diagnosed with Barrett's esophagus underwent UHR OCT. Imaging was performed at 1.3 mu m wavelengths with - 5 pm axial and - 15 pm transverse resolutions using a 1.8 mm/ diameter linear-scanning catheter introduced through the accessory channel of a standard endoscope. OCT images were compared with endoscopic diagnosis and pinch biopsy histological appearances. Results: UHR OCT images of normal esophagus, Barrett's esophagus, high grade dysplasia and esophageal adenocarcinoma were evaluated. UHR OCT images of the normal esophagus exhibited characteristic layered architecture with uniform epithelium, while images of Barrett's esophagus corresponded to crypt-like glandular structures. High grade dysplasia and esophageal adenocarcinoma images exhibited more heterogeneous structures corresponding to irregular, heterogeneous tissue morphology from distorted and cribriform or villiform glandular architecture. Fine features can be discerned more clearly with endoscopic UHR OCT. Conclusions: This study evaluated new endoscopic OCT technology and demonstrated the feasibility of carrying out UHR OCT imaging in conjunction with standard endoscopy for in vivo real-time imaging of Barrett's esophagus, dysplasia, and esophageal adenocarcinoma. A survey of normal and abnormal upper gastrointestinal tissues was performed using a research prototype OCT system with the highest axial resolution to date, and can serve as a baseline for future inves- C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. VA Boston Healthcare Syst, Boston, MA USA. Light Lab Imaging Inc, Westford, MA USA. RP Mashimo, H (reprint author), VAMC Gastroenterol 111, 150 S Huntington Ave, Boston, MA 02130 USA. EM hmashimo@hms.harvard.edu FU NCI NIH HHS [R01-CA75289-10] NR 18 TC 92 Z9 92 U1 2 U2 7 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JUL PY 2007 VL 39 IS 7 BP 599 EP 605 DI 10.1055/s-2007-966648 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 195JG UT WOS:000248407900004 PM 17611914 ER PT J AU Meeker, JD Calafat, AM Hauser, R AF Meeker, John D. Calafat, Antonia M. Hauser, Russ TI Di(2-ethylhexyl) phthalate metabolites may alter thyroid hormone levels in men SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; endocrine disruption; epidemiology; hormone; phthalates; thyroid; urinary metabolites ID ENDOCRINE-DISRUPTING CHEMICALS; HUMAN URINE; DI-(2-ETHYLHEXYL) PHTHALATE; ENVIRONMENTAL CHEMICALS; QUANTITATIVE DETECTION; OXIDATIVE METABOLITES; HEXYL) PHTHALATE; SEMEN QUALITY; MALE RATS; EXPOSURE AB BACKGROUND: Phthalates are used extensively in many personal-care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. A limited number of animal studies suggest that exposure to phthalates may be associated with altered thyroid function, but human data are lacking. METHODS: Concurrent samples of urine and blood were collected from 408 men. We measured urinary concentrations of mono (2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di(2-ethylhexyl) phthalate (DEHP), and other phthalate monoester metabolites, along with serum levels of free thyroxine (T-4), total triiodothyronine (T-3), and thyroid-stimulating hormone (TSH). Oxidative metabolites of DEHP were measured in urine from only 208 of the men. RESULTS: We found an inverse association between MEHP urinary concentrations and free T-4 and T-3 serum levels, although the relationships did not appear to be linear when MEHP concentrations were categorized by quintiles. There was evidence of a plateau at the fourth quintile, which was associated with a 0.11 ng/dL decrease in free T-4 [95% confidence interval (CI), -0.18 to -0-03] and a 0.05 ng/mL decrease in T-3 (95% CI, -0.10 to 0.01) compared with the first (lowest) MEHP quintile. The inverse relationship between MEHP and free T-4 remained when we adjusted for oxidative metabolite concentrations; this simultaneously demonstrated a suggestive positive association with free T-4. CONCLUSIONS: Urinary MEHP concentrations may be associated with altered free T-4 and/or total T-3 levels in adult men, but additional study is needed to confirm the observed findings. Future studies must also consider oxidative DEHP metabolites relative to MEHP as a potential marker of metabolic susceptibility to DEHP exposure. C1 Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab & In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES09718, R01 ES009718] NR 42 TC 124 Z9 133 U1 4 U2 20 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 JUL PY 2007 VL 115 IS 7 BP 1029 EP 1034 DI 10.1289/ehp.9852 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 185MW UT WOS:000247716100028 PM 17637918 ER PT J AU Cavallari, JM Eisen, EA Chen, JC Fang, SC Dobson, CB Schwartz, J Christiani, DC AF Cavallari, Jennifer M. Eisen, Ellen A. Chen, Jiu-Chiuan Fang, Shona C. Dobson, Christine B. Schwartz, Joel Christiani, David C. TI Night heart rate variability and particulate exposures among boilermaker construction workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE environmental cardiology; heart rate variability; occupational; particulate exposures; welders ID CONCENTRATED AMBIENT PARTICLES; AIR-POLLUTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; TRANSITION-METALS; HEALTHY-SUBJECTS; MATTER; FINE; ASSOCIATION; SLEEP AB BACKGROUND: Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and Metal-rich, occupational particulate exposures remains unclear. OBJECTIVE: Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM2.5 exposures. METHODS: We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNNi (SDNN for all 5-min segments) were summarized over 24-hr, day (0730-2130 hours), and night (0000-0700 hours) periods. PM2.5 (particulate matter with an aerodynamic diameter <= 2.5 mu m) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors. RESULTS: Mean (+/- SD) PM2.5 exposure was 0.73 +/- 0.50 mg/m(3) and ranged from 0.04 to 2.70 mg/m(3). We observed a consistent inverse exposure-response relationship, with a decrease in all HRV measures with increased PM2.5 exposure. However, the decrease was most pronounced at night, where a 1-mg/m(3) increase in PM2.5 was associated with a change of -8.32 [95% confidence interval (CI), -16.29 to -0.35] msec nighttime rMSSD, -14.77 (95% CI, -31.52 to 1.97) msec nighttime SDNN, and -8.37 (95% CI, -17.93 to 1.20) msec nighttime SDNNi, after adjusting for nonworking nighttime HRV, age, and smoking. CONCLUSION: Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,SPH1-1402, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Chen, JC/I-2261-2016 FU NIEHS NIH HHS [R01 ES009860, P30 ES000002, ES009860, ES00002]; NIOSH CDC HHS [T42 OH008416] NR 44 TC 25 Z9 26 U1 0 U2 6 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 JUL PY 2007 VL 115 IS 7 BP 1046 EP 1051 DI 10.1289/ehp.10019 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 185MW UT WOS:000247716100031 PM 17637921 ER PT J AU Giraldez, RR Nicolau, JC Corbalan, R Gurfinkel, EP Juarez, U Lopez-Sendon, J Parkhomenko, A Molhoek, P Mohanavelu, S Morrow, DA Antman, EM AF Giraldez, Roberto R. Nicolau, Jose Carlos Corbalan, Ramon Gurfinkel, Enrique P. Juarez, Ursulo Lopez-Sendon, Jose Parkhomenko, Alexander Molhoek, Peter Mohanavelu, Satishkumar Morrow, David A. Antman, Elliott M. TI Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis SO EUROPEAN HEART JOURNAL LA English DT Article DE STEMI; enoxaparin; fibrin-specific lytics; streptokinase ID TISSUE PLASMINOGEN-ACTIVATOR; ANTITHROMBIN THERAPY; THROMBOLYSIS; TRIAL; REPERFUSION; ASPIRIN; MORTALITY AB Aims We compared outcomes of ST-elevation myocardial infarction (STEMI) patients randomized to a strategy of either enoxaparin or unfractionated heparin (UFH) to support fibrinolysis. Methods and results In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction Study 25 (ExTRACT-TIMI 25) trial, 20 479 patients undergoing fibrinolysis for STEMI with a fibrin-specific agent (N = 16 283) or streptokinase (SK) IN = 4139) were randomized to enoxaparin throughout their hospitalization or UFH for at [east 48 h. The primary end point of death or nonfatal recurrent MI through 30 days occurred in 12.0% of patients in the UFH and 9.8% in the enoxaparin groups when treated with fibrin-specific lytics [odds ratio(adjusted) (ORadj) 0.78; 95% Cl 0.70-0.87; P < 0.001] and 11.8 vs. 10.2%, respectively, when treated with SK (ORadj 0.83; 95% CI 0.66-1.04; P = 0-10; P-interaction = 0.58). Major bleeding rates including intracranial hemorrhage within the fibrin specific cohort were 1.2 and 2.0% in the UFH and enoxaparin groups, respectively (P < 0.001) and 2.0% in UFH and 2.4% in enoxaparin patients in the SK cohort (P = 0.16). Interaction tests between antithrombin- and lytic-type were non-significant (P = 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (ORadj 0.82; 95% Cl 0.74-0.91; P < 0.001) and favoured enoxaparin in the SK cohort (ORadj 0.89; 95% Cl 0.72-1.10; P = 0.29; P-interaction = 0.53). Conclusion The benefits of an enoxaparin strategy over UFH were observed in both SK and fibrin -specific-treated STEMI patients. Therefore, an enoxaparin strategy is preferred over UFH to support fibrinolysis for STEMI regardless of lytic agent. C1 Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Cardiovasc,TIMI Study Grp, Boston, MA 02115 USA. Univ Sao Paulo, Sch Med, Inst Heart, Sao Paulo, Brazil. Pontificia Univ Catolica Chile, Dept Cardiovasc Dis, Santiago, Chile. Fdn Favaloro, Buenos Aires, DF, Argentina. Inst Nacl Cardiol Ignacio Chavez, Coronary Care Unit, Mexico City, DF, Mexico. H Gregorio Maranon, Madrid, Spain. Inst Cardiol, Kiev, Ukraine. RP Giraldez, RR (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Cardiovasc,TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM rgiraidez@partners.org RI Nicolau, Jose/E-1487-2012 NR 16 TC 30 Z9 36 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2007 VL 28 IS 13 BP 1566 EP 1573 DI 10.1093/eurheartj/ehm179 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 193JZ UT WOS:000248271600009 PM 17562672 ER PT J AU Partridge, A Gelber, S Gelber, RD Castiglione-Gertsch, M Goldhirsch, A Winer, E AF Partridge, Ann Gelber, Shari Gelber, Richard D. Castiglione-Gertsch, Monica Goldhirsch, Aron Winer, Eric TI Age of menopause among women who remain premenopausal following treatment for early breast cancer: Long-term results from International Breast Cancer Study Group Trials V and VI SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE breast cancer; young women; premature menopause; fertility ID INDUCED OVARIAN FAILURE; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; ADJUVANT CHEMOTHERAPY; NATURAL MENOPAUSE; CHILDHOOD-CANCER; SURVIVORS; FERTILITY; HEALTH; IMPACT AB Background: The likelihood of Premature menopause has not been thoroughly explored in women who remain premenopausal after adjuvant chemotherapy for breast cancer. Methods: We used data from the International Breast Cancer Study Group (IBCSG) Trials V and VI. Trial V enrolled 1407 eligible premenopausal women randomised to no systemic therapy (No CT) or 1 cycle of perioperative CMF-based chemotherapy (PeCT) if node negative, and 6 cycles of CMF-based chemotherapy postoperatively (CMF x 6) or 1 cycle perioperative CMF-based chemotherapy plus CMF x 6 postoperatively (CMF x 7) if node positive. From Trial VI (a 2 x 2 factorial designed study of 3 versus 6 initial cycles of CMF and a reintroduction of three additional courses of CMF), we included 375 women randomised to receive only six initial cycles of CMF (CMF x 6). Findings: We excluded women who reported no menses during 12-24 months after randomisation (N = 934), hysterectomy (N = 16) or bilateral oophorectomy (N = 8), or missing menses data (N = 57), creating a cohort of 767 women; 540 women had been randomised to PeCT or no CT, 227 randomised to CMF x 6 or 7. A Cox proportional hazards model revealed that CMF x 6 or 7 (HR = 2.03, p < 0.0001) and temporary amenorrhea (HR = 1.96, p < 0.0001) were associated with Premature menopause. Interpretation: Women who remain premenopausal after 6 or 7 cycles of CMF-based chemotherapy have a higher likelihood of going through menopause at an earlier age than women who received little or no chemotherapy Temporary cessation of menses appears to be a marker for earlier onset of menopause. These findings may assist women and clinicians when making treatment and reproductive decisions after a diagnosis of breast cancer. (c) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. IBCSG Coordinating Ctr, Bern, Switzerland. European Inst Oncol, Milan, Italy. Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Partridge, A (reprint author), Dana Farber Canc Inst, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org FU NCI NIH HHS [CA75362] NR 35 TC 77 Z9 79 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2007 VL 43 IS 11 BP 1646 EP 1653 DI 10.1016/j.ejca.2007.04.006 PG 8 WC Oncology SC Oncology GA 206QN UT WOS:000249198100011 PM 17512721 ER PT J AU Cocks, K Cohen, D Wisloff, F Sezerc, O Lee, S Hippe, E Gimsing, P Turesson, I Hajek, R Smith, A Graham, L Phillips, A Stead, M Velikova, G Brown, J AF Cocks, K. Cohen, D. Wisloff, F. Sezerc, O. Lee, S. Hippe, E. Gimsing, P. Turesson, I. Hajek, R. Smith, A. Graham, L. Phillips, A. Stead, M. Velikova, G. Brown, J. CA EORTIC Quality Life Grp TI An internadional field study of the reliability and validity of a disease-specfic questionnanire module (the QLQ-MY20) in assessing the quality of life of patients with multiple myeloma SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE quality of life; multiple myeloma; validation; questionnaires; QLQ-C30; QLQ-MY24; QLQ-MY20 AB Aim: To test the reliability, validity and sensitivity of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-MY24 questionnaire, designed to assess the quality of life of myeloma patients with the QLQ-C30. Methods: The study was carried out through the EORTC Quality of Life Group using clinical trials in seven countries. All trials used the QLQ-C30 and QLQ-MY24 at baseline and a follow-up timepoint. Results: Two hundred and forty patients participated. The questionnaires were acceptable to patients. The hypothesised scale structure (disease symptoms, side-effects, body image and future perspective) was confirmed by multi-trait scaling, internal consistency and correlation analysis. Most scales demonstrated sensitivity to change and discriminated between clinically different patients. The social support scale (4 items) was removed due to observed ceiling effects. Conclusion: The final questionnaire contains 20 items, QLQ-MY20, and is a reliable and valid instrument recommended for use with the QLQ-C30 in myeloma patients. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Leeds, Clin Trials Res Unit, Leeds LS2 9NG, W Yorkshire, England. Univ Oslo, Ulleval Univ Hosp, Dept Haematol, N-0316 Oslo, Norway. Univ Oslo, Fac Med, N-0316 Oslo, Norway. Univ Hosp Charite Berlin, Dept Hematol & Oncol, Berlin, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Herlev Hosp, Dept Haematol, DK-2730 Herlev, Denmark. Rigshosp, Dept Haematol, DK-2100 Copenhagen, Denmark. Malmo Univ Hosp, Malmo, Sweden. MU Brno, Fac Med, Brno, Czech Republic. Fac Hosp Brno, Dept Internal Med & Hematooncol, Brno, Czech Republic. Southampton Gen Hosp, Southampton SO9 4XY, Hants, England. St James Univ Hosp, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England. RP Cocks, K (reprint author), Univ Leeds, Clin Trials Res Unit, 17 Springfield Mt, Leeds LS2 9NG, W Yorkshire, England. EM k.cocks@leeds.ac.uk RI Cohen, Dena/F-4938-2012 NR 13 TC 55 Z9 56 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2007 VL 43 IS 11 BP 1670 EP 1678 DI 10.1016/j.ejca.2007.04.022 PG 9 WC Oncology SC Oncology GA 206QN UT WOS:000249198100014 PM 17574838 ER PT J AU Chokshi, R Restrepo, MI Weeratunge, N Frei, CR Anzueto, A Mortensen, EM AF Chokshi, R. Restrepo, M. I. Weeratunge, N. Frei, C. R. Anzueto, A. Mortensen, E. M. TI Monotherapy versus combination antibiotic therapy for patients with bacteremic Streptococcus pneumoniae community-acquired pneumonia SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID PNEUMOCOCCAL PNEUMONIA; MORTALITY; GUIDELINES AB The purpose of this study was to examine the impact of antimicrobial monotherapy vs combination therapy on length of stay and mortality for patients with Streptococcus pneumoniae pneumonia. Thirty-nine percent of patients received monotherapy, while 61% received combination therapy. Although there was no significant difference in mortality (OR 1.25, 95% CI = 0.25-6.8), there was a significant increase in length of stay for patients who received combination therapy (p = 0.02). Patients with bacteremic pneumococcal pneumonia treated with empiric combination therapy had no significant difference in mortality; however, they did have increased length of stay after adjusting for severity of illness. Randomized controlled trials are needed to determine what is the optimal empiric antimicrobial regime for patients with community-acquired pneumonia. C1 Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78230 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Mortensen, EM (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, 11C6,7400 Merton Minter Blvd, San Antonio, TX 78230 USA. EM mortensene@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 NR 14 TC 20 Z9 20 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JUL PY 2007 VL 26 IS 7 BP 447 EP 451 DI 10.1007/s10096-007-0307-3 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 188OX UT WOS:000247930300001 PM 17534677 ER PT J AU Sabado, RL Babcock, E Kavanagh, DG Tjomsland, V Walker, BD Lifson, JD Bhardwaj, N Larsson, M AF Sabado, Rachel L. Babcock, Ethan Kavanagh, Daniel G. Tjomsland, Veronica Walker, Bruce D. Lifson, Jeffrey D. Bhardwaj, Nina Larsson, Marie TI Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen pathway; antigen presentation; antigen processing; dendritic cells; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR-MEDIATED UPTAKE; IMMUNOGLOBULIN G1 B12; CD8 T-CELLS; DC-SIGN; MANNOSE RECEPTOR; INTRAVAGINAL INOCULATION; CROSS-PRESENTATION; RHESUS MACAQUES; TYPE-1 GP120 AB The outcome following HIV infection depends on the nature and durability of the HIV-specific T cell response induced initially. The activation of protective T cell responses depends upon dendritic cells (DC), antigen-presenting cells which have the capacity to process and present viral antigens. DC pulsed with aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune responses and promote virologic control in chronically HIV-1-infected subjects. To gain an understanding of this phenomenon, we characterized the steps involved in the presentation of antigens derived from aldrithiol-2-treated vs. infectious HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C-type lectins expressed by the DC. Inhibitor studies showed that presentation on MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner, both at the cell surface and within endosomes, and access to the classical endosomal processing pathway. MHC class II presentation of HIV-associated antigens was dependent on active endocytosis, probably receptor-mediated, and subsequent degradation of virions in acidified endosomes in the DC. Our study brings forth new facts regarding the binding, uptake, and processing of chemically inactivated virions leading to efficient antigen presentation and should aid in the design of more effective HIV vaccines. C1 Linkoping Univ, S-58185 Linkoping, Sweden. NYU, Sch Med, Dept Pathol & Med, New York, NY USA. Massachusetts Gen Hosp, Partner AIDS Res Ctr, Charlestown, MA USA. Howard Hughes Med Inst, Chevy Chase, MD USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Larsson, M (reprint author), Linkoping Univ, S-58185 Linkoping, Sweden. EM maria@imk.liu.se FU NCI NIH HHS [N01 CO12400]; NIAID NIH HHS [AI55274, AI61684, F32 AI058457-03, F32 AI058457, AI57127, AI52731, AI44628] NR 67 TC 28 Z9 28 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2007 VL 37 IS 7 BP 1752 EP 1763 DI 10.1002/eji.200636981 PG 12 WC Immunology SC Immunology GA 187DS UT WOS:000247828200008 PM 17534864 ER PT J AU Zeck, GM Masland, RH AF Zeck, Gunther M. Masland, Richard H. TI Spike train signatures of retinal ganglion cell types SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ganglion; rabbit; retina; spike timing ID LATERAL GENICULATE-NUCLEUS; RECEPTIVE-FIELD PROPERTIES; PRIMARY VISUAL-CORTEX; LOCAL EDGE DETECTORS; RABBIT RETINA; MAMMALIAN RETINA; RESPONSE VARIABILITY; MAXIMUM-LIKELIHOOD; EYE TELLS; IN-VITRO AB The mammalian retina deconstructs the visual world using parallel neural channels, embodied in the morphological and physiological types of ganglion cells. We sought distinguishing features of each cell type in the temporal pattern of their spikes. As a first step, conventional physiological properties were used to cluster cells in eight types by a statistical analysis. We then adapted a method of P. Reinagel et al. (1999: J. Neurophysiol., 81, 2558-2569) to define epochs within the spike train of each cell. The spike trains of many cells were found to contain robust patterns that are defined by the (averaged) timing of successive interspike intervals in brief activity epochs. The patterns were robust across four different types of visual stimulus. Although the patterns are conserved in different visual environments, they do not prevent the cell from signaling the strength of its response to a particular stimulus, which is expressed in the number of spikes contained in each coding epoch. Clustering based on the spike train patterns alone showed that the spike train patterns correspond, in most but not all cases, to cell types pre-defined by traditional criteria. That the congruence is less than perfect suggests that the typing of rabbit ganglion cells may need further refinement. Analysis of the spike train patterns may be useful in this regard and for distinguishing the many unidentified ganglion cell types that exist in other mammalian retinas. C1 Max Planck Inst Neurobiol, D-82152 Martinsried, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Zeck, GM (reprint author), Max Planck Inst Neurobiol, D-82152 Martinsried, Germany. EM zeck@neuro.mpg.de RI X, Simon/F-4678-2011; Zeck, Gunther/H-7419-2013; OI Zeck, Gunther/0000-0003-3998-9883 NR 62 TC 34 Z9 34 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2007 VL 26 IS 2 BP 367 EP 380 DI 10.1111/j.1460-9568.2007.05670.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 197ZX UT WOS:000248597600009 PM 17650112 ER PT J AU Kassarjian, A Brisson, M Palmer, WE AF Kassarjian, Ara Brisson, Melanie Palmer, William E. TI Femoroacetabular impingement SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE hip; impingement; labrum; MR; arthrography; MR arthrography; femoroacetabular; MRI; cam; pincer ID MR ARTHROGRAPHY; FEMORAL-NECK; HIP PAIN; RETROVERSION; ACETABULUM; OSTEOTOMY AB Femoroacetabular impingement is a relatively recently appreciated "idiopathic" cause of hip pain and degenerative change. Two types of impingement have been described. The first, cam impingement, is the result of an abnormal morphology of the proximal femur, typically at the femoral head-neck junction. Cam impingement is most common in young athletic males. The second, pincer impingement, is the result of an abnormal morphology or orientation of the acetabulum. Pincer impingement is most common in middle-aged women. This article reviews the imaging findings of cam and pincer type femoroacetabular impingement. Recognition of these entities will help in the selection of the appropriate treatment with the goal of decreasing the likelihood of early degenerative change of the hip. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Ctr Hosp Univ Quebec, Dept Radiol, Quebec City, PQ, Canada. Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Kassarjian, A (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Paseo Castellana 141,Edifico Cuzco 4 Planta 18,OF, Madrid 28046, Spain. EM akassarjian@partners.org NR 18 TC 44 Z9 44 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD JUL PY 2007 VL 63 IS 1 BP 29 EP 35 DI 10.1016/j.ejrad.2007.03.020 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 190KX UT WOS:000248058800005 PM 17485190 ER PT J AU Scarcelli, G Zhou, Y Shih, Y AF Scarcelli, G. Zhou, Y. Shih, Y. TI Random delayed-choice quantum eraser via two-photon imaging SO EUROPEAN PHYSICAL JOURNAL D LA English DT Article ID ELECTRON-PARAMAGNETIC-RES; COMPLEMENTARITY; INTERFERENCE; ERASURE; INTERFEROMETER; COHERENCE; MECHANICS; TIME AB We report on a delayed-choice quantum eraser experiment based on a two-photon imaging scheme using entangled photon pairs. After the detection of a photon which passed through a double-slit, a random delayed choice is made to erase or not erase the which-path information by the measurement of its distant entangled twin; the particle-like and wave-like behavior of the photon are then recorded simultaneously and respectively by only one set of joint detection devices. The present eraser takes advantage of two-photon imaging. The complete which-path information of a photon is transferred to its distant entangled twin through a "ghost" image. The choice is made on the Fourier transform plane of the ghost image between reading "complete information" or "partial information" of the double-path. C1 Univ Maryland Baltimore Cty, Dept Phys, Baltimore, MD 21250 USA. Univ Bari, Dipartimento Interateneo Fis, I-70126 Bari, Italy. RP Scarcelli, G (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM gscarcelli@partners.org OI scarcelli, giuliano/0000-0002-1736-077X NR 30 TC 9 Z9 9 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1434-6060 J9 EUR PHYS J D JI Eur. Phys. J. D PD JUL PY 2007 VL 44 IS 1 BP 167 EP 173 DI 10.1140/epjd/e2007-00164-y PG 7 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA 188QW UT WOS:000247935400020 ER PT J AU Berson, EL AF Berson, Eliot L. TI Long-term visual prognoses in patients with retinitis pigmentosa: The Ludwig von Sallmann lecture SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT 17th Meeting of the International Congress of Eye Research CY OCT 30, 2006 CL Buenos Aires, ARGENTINA DE retinitis pigmentosa; retinal degeneration; retina; cones; electroretinogram; vitamin A; genetic disease; night blindness ID DISEASE COURSE; VITAMIN-A; ELECTRORETINOGRAPHY; MUTATIONS; AMPLITUDE AB Retinitis pigmentosa can be followed over almost its entire course with narrow bandpassed, computer averaged cone electroretinograms (ERGs). The long-term rate of decline of these responses can be described by an exponential function. A cone ERG actuarial table based on 1039 patients and 6553 visits is presented to show the estimated number of years for an average patient with a given 30-Hz cone ERG amplitude to decline to 0.05 mu V (i.e. virtual blindness). The table is based on a projected rate of loss of 10% of remaining cone ERG amplitude per year for those not on treatment and 8.3% per year for those on treatment with vitamin A palmitate 15,000 IU/day. The table can be used to provide an estimate of the average long-term visual prognosis from a single visit; more precise estimates for a specific patient require several additional visits over 2- to 3-year intervals. Evidence is presented to support the idea that patients with a projected cone amplitude of 3.5 mu V or greater at age 40 (about 25 % of our patient population with typical retinitis pigmentosa) would be expected, on average, to retain some useful vision for their entire lives without treatment. Knowledge of the amount of remaining cone function in the ERG often reduces patient anxiety and helps patients plan for their future. (c) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Study Retinal Degenerat, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [R37 EY000169, EY00169, R01 EY000169, R01 EY000169-36] NR 18 TC 46 Z9 46 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 2007 VL 85 IS 1 BP 7 EP 14 DI 10.1016/j.exer.2007.03.001 PG 8 WC Ophthalmology SC Ophthalmology GA 196UK UT WOS:000248507500003 PM 17531222 ER PT J AU Catley, L Hideshima, T Chauhan, D Neri, P Tassone, P Bronson, R Song, WH Tai, YT Munshi, NC Anderson, KC AF Catley, Laurence Hideshima, Teru Chauhan, Dharminder Neri, Paola Tassone, Pierfrancesco Bronson, Roderick Song, Weihua Tai, Yu-Tzu Munshi, Nikhil C. Anderson, Kenneth C. TI Alkyl phospholipid perifosine induces myeloid hyperplasia in a murine myeloma model SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HUMAN LEUKEMIC-CELLS; SOFT-TISSUE SARCOMA; PHASE-II; MILTEFOSINE HEXADECYLPHOSPHOCHOLINE; ANTINEOPLASTIC ACTIVITY; ANTITUMOR-ACTIVITY; LYMPHOID TISSUES; ORAL MILTEFOSINE; SOLID TUMORS; THYMUS AB Objectives. Alkyl-lysophospholipids area novel class of antitumor agents. Perifosine is a novel alkyl-lysophospholipid that can induce apoptosis in multiple myeloma (MM) tumor cells, both in vitro and in vivo. We investigated the effects of perifosine on the peripheral blood, bone marrow, and spleen of mice inoculated with subcutaneous plasmacytomas. Methods. Immunocompromised mice were inoculated with myeloma cell lines and treated with oral perifosine in either a daily or weekly schedule, or with vehicle only. When plasmacytomas reached 2 cm, mice were sacrificed. Terminal blood was analyzed with a Coulter counter, and counts were confirmed by light microscopy. Marrow and spleen were also analyzed by light microscopy. Results. In control mice, mean hemoglobin was 12 g/dL, white blood cell (WBC) count 7 x 10(9)/L, and mean platelet count was 292 X 109/L. In contrast, the respective values for mice treated with perifosine weekly were 11 g/dL, 9 x 10(9)/L, and 944 x 10(9)/L; and for mice treated with perifosine daily were 10 g/dL, 11 x 10(9)/L, and 752 x 10(9)/L. The increase in WBCs was due, predominantly, to, a neutrophilia. Compared to control mice, perifosine treatment induced marrow hypercellularity and splenic white pulp expansion. Conclusions. These findings have clinical relevance because myeloid suppression is a dose-limiting toxicity of many cytotoxic agents, and myeloid hyperplasia is usually only observed in the setting of growth factor stimulation. Coupled with its remarkable in vitro MM cytotoxicity, these results strongly support the use of perifosine in clinical trials for patients with MM. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Catley, L (reprint author), Mater Adult Hosp, 35 Raymond Tce, Brisbane, Qld 4101, Australia. EM laurence.catley@mater.org.au RI Catley, Laurence/E-5313-2013 FU PHS HHS [P0178378, R0150947] NR 38 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2007 VL 35 IS 7 BP 1038 EP 1046 DI 10.1016/j.exphem.2007.03.020 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 186TL UT WOS:000247801000004 PM 17588472 ER PT J AU Shaffer, J Villard, J Means, TK Alexander, S Dombkowski, D Dey, BR McAfee, S Ballen, KK Saidman, S Preffer, FI Sachs, DH Spitzer, TR Sykes, M AF Shaffer, Juanita Villard, Jean Means, Terry K. Alexander, Stephen Dombkowski, David Dey, Bimalangshu R. McAfee, Steven Ballen, Karen K. Saidman, Susan Preffer, Frederic I. Sachs, David H. Spitzer, Thomas R. Sykes, Megan TI Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; REFRACTORY HEMATOLOGIC MALIGNANCIES; IMMUNOLOGICAL SELF-TOLERANCE; DONOR LYMPHOCYTE INFUSION; ANTIGEN-PRESENTING CELLS; IN-VIVO; HLA-DPB1 DISPARITY; GRAFT-REJECTION; MIXED CHIMERISM AB Objective. We have evaluated T-cell reconstitution and reactivity in patients receiving non-myeloablative haploidentical hematopoietic cell transplantation (HCT) protocols involving an anti-CD2 monoclonal antibody (MEDI 507) to treat chemorefractory hematopoietic malignancies. Methods. Three cohorts of four patients each and one cohort of six patients received one of four Medi-507-based regimens, all of which included cyclophosphamide, thymic irradiation, and a short posttransplantation course of cyclosporine. Results. Following marked T-cell depletion, initially recovering CD4 and CD8 T cells were mainly memory-type cells. A high percentage of CD4 T cells expressed high levels of CD25 in recipients of all protocols, except the only protocol to include fludarabine, early post-HCT. CD25 expression varied inversely with T-cell concentrations in blood. CD25 high CD4 T cells expressed Foxp3 and cytotoxic T-lymphocyte-associated protein 4, indicating that they were regulatory T cells (Treg). Conclusions. Fludarabine treatment prevents Treg enrichment after haploidentical nonmyeloablative stem cell transplantation, presumably by depleting recipient Tregs. In vitro analyses of allorecognition were consistent with a cytokine-mediated rejection process in one case and in another provided proof of principle that mixed chimerism achieved without graft-vs-host disease induces donor- and recipient-specific tolerance. More reliable achievement of this outcome could provide a promising strategy for organ allograft tolerance induction. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Sect,Transplantat Biol R, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Sect,Transplantat Biol R, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [R01 CA079986-01A1, R01 CA79986, R01 CA079989, R01 CA79989]; NHLBI NIH HHS [R01 HL63474] NR 62 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2007 VL 35 IS 7 BP 1140 EP 1152 DI 10.1016/j.exphem.2007.03.018 PG 13 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 186TL UT WOS:000247801000015 PM 17588483 ER PT J AU Butsch, PO Cudkowicz, ME AF Butsch, Patrick O. Cudkowicz, Merit E. TI Is erythropoietin a potential therapy for amyotrophic lateral sclerosis? SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID MOTOR-NEURON DISEASE; ZINC SUPEROXIDE-DISMUTASE; E EPSILON-4 ALLELE; IN-VIVO; CORTICAL-NEURONS; CONTROLLED TRIAL; CLINICAL-TRIALS; SPORADIC ALS; FAMILIAL ALS; GENE C1 Neurol Clin Trials Univ, Dept Neurol, Charlestown, MA 02129 USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St,Room 2274, Boston, MA 02129 USA. EM mcudkowicz@partners.org NR 63 TC 3 Z9 3 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2007 VL 206 IS 1 BP 11 EP 15 DI 10.1016/j.expneurol.2007.04.001 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 187CN UT WOS:000247825000002 PM 17498699 ER PT J AU Meier, A Altfeld, M AF Meier, Angela Altfeld, Marcus TI Toll-like receptor signaling in HIV-1 infection: a potential target for therapy? SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Editorial Material ID SIMPLEX-VIRUS TYPE-2; GASTROINTESTINAL-TRACT; DENDRITIC CELLS; T-CELLS; SUPPRESSION; REPLICATION; VIRULENCE; DEPLETION; RESPONSES; DISEASE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Bldg 149,13th St,6th Floor, Charlestown, MA 02129 USA. EM ameier@partners.org; maltfeld@partners.org NR 36 TC 6 Z9 7 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JUL PY 2007 VL 5 IS 3 BP 323 EP 326 DI 10.1586/14787210.5.3.323 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228VD UT WOS:000250759800001 PM 17547495 ER PT J AU Rosenbaum, JT Martin, TM Farris, KH Rosenbaum, RB Neuwelt, EA AF Rosenbaum, James T. Martin, Tammy M. Farris, Kendra H. Rosenbaum, Richard B. Neuwelt, Edward A. TI Can medical schools teach high school students to be scientists? SO FASEB JOURNAL LA English DT Article DE education; secondary school; science; scientific inquiry AB The preeminence of science in the United States is endangered for multiple reasons, including mediocre achievement in science education by secondary school students. A group of scientists at Oregon Health and Science University has established a class to teach the process of scientific inquiry to local high school students. Prominent aspects of the class include pairing of the student with a mentor; use of a journal club format; preparation of a referenced, hypothesis driven research proposal; and a "hands-on" laboratory experience. A survey of our graduates found that 73% were planning careers in health or science. In comparison to conventional science classes, including chemistry, biology, and algebra, our students were 7 times more likely to rank the scientific inquiry class as influencing career or life choices. Medical schools should make research opportunities widely available to teenagers because this experience dramatically affects one's attitude toward science and the likelihood that a student will pursue a career in science or medicine. A federal initiative could facilitate student opportunities to pursue research. C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Rosenbaum, JT (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd L467Ad, Portland, OR 97239 USA. EM rosenbaj@ohsu.edu NR 4 TC 7 Z9 7 U1 1 U2 5 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 JUL PY 2007 VL 21 IS 9 BP 1954 EP 1957 DI 10.1096/fj.06-7845lsf PG 4 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 182JG UT WOS:000247500300005 PM 17351126 ER PT J AU Poulaki, V Iliaki, E Mitsiades, N Mitsiades, CS Paulus, YN Bula, DV Gragoudas, ES Miller, JW AF Poulaki, Vassiliki Iliaki, Eirini Mitsiades, Nicholas Mitsiades, Constantine S. Paulus, Yiannis N. Bula, Deisy V. Gragoudas, Evangelos S. Miller, Joan W. TI Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis SO FASEB JOURNAL LA English DT Article DE lipopolysaccharide; EIU; inflammatory eye disease ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; ALPHA MESSENGER-RNA; HEAT-SHOCK PROTEINS; NF-KAPPA-B; DIABETIC-RETINOPATHY; GENE-EXPRESSION; IN-VIVO AB Heat shock protein (Hsp) 90 inhibitors, such as 17-allylamino-17-demethoxy-geldanamycin (17AAG), constitute promising novel therapeutic agents. We investigated the anti-inflammatory activity of 17AAG in endotoxin-induced uveitis (EIU) in rats. After the induction of EIU with a footpad injection of lipopolysaccharide (LPS), female Lewis rats received a single intraperitoneal. (i.p.) injection of 17-AAG or vehicle. Twenty-four hours later, the retinas were extracted and assayed for leukocyte adhesion; blood-retinal barrier breakdown; VEGF, TNF-alpha, IL-1 beta, and CD14 protein levels; NF-kappa B and HIF-1 alpha activity; hsp90 and 70 levels and expression and phosphorylation of the tight junction proteins ZO-1 and occludin. 17-AAG treatment significantly suppressed the LPS-induced increase in retinal leukocyte adhesion; vascular leakage; NF-kappa B, HIF-1 alpha, p38, and PI-3K activity; and VEGF, TNF-alpha, and IL-1 beta levels. 17-AAG also suppressed phosphorylation of ZO-1 and occludin by inhibiting their association with p38 and PI-3K. Although 17-AAG treatment did not reduce the LPS-induced increase in total CD14 levels in leukocytes, it significantly decreased membrane CD14 levels. These data suggest that Hsp90 inhibition suppresses several cardinal manifestations of endotoxin-induced uveitis in the rat. 17-AAG has demonstrated a favorable safety profile in clinical trials in cancer patients and represents a promising therapeutic agent for the treatment of inflammatory eye diseases. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Angiogenesis Laser Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Angiogenesis Laser Lab, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu NR 56 TC 54 Z9 56 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JUL PY 2007 VL 21 IS 9 BP 2113 EP 2123 DI 10.1096/fj.06-7637com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 182JG UT WOS:000247500300021 PM 17400913 ER PT J AU Vidal, M AF Vidal, M. TI Interactome networks SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Vidal, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vidal, M.] CCSB, Boston, MA 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 54 EP 54 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800089 ER PT J AU Liu, YE Pu, WP Wang, JD Kang, JX Shi, YE AF Liu, Yiliang E. Pu, Weiping Wang, Jingdong Kang, Jing X. Shi, Y. Eric TI Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids SO FEBS JOURNAL LA English DT Article DE breast cancer prevention; DPA; EPA; n-3 fatty acid; pregnancy ID FATTY-ACID COMPOSITION; BREAST-CANCER RISK; INHIBITOR-RELATED GENE; LIPID-BINDING PROTEIN; TRANSGENIC MICE; ADIPOSE-TISSUE; DOCOSAHEXAENOIC ACID; LACTATION HISTORY; GROWTH INHIBITOR; PROSTATE-CANCER AB The protective effect of early pregnancy against breast cancer can be attributed to the transition from undifferentiated cells in the nulliparous to the differentiated mature cells during pregnancy. Considerable evidence suggests strongly that the n-3 polyunsaturated fatty acid (PUFA) content of adipose breast tissue is inversely associated with an increased risk of breast cancer. Here, we report that there was a decrease in the n-6/n-3 PUFA ratio and a significant increase in concentration of n-3 PUFA docosapentaenoic acid and eicosapentaenoic acid in the pregnant gland. The functional role of n-3 PUFAs on differentiation was supported by the studies in the fat-1 transgenic mouse, which converts endogenous n-6 to n-3 PUFAs. Alternation of the n-6/n-3 ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid, in the mammary gland of fat-1 mouse resulted in development of lobulo-alveolar-like structure and milk protein beta-casein expression, mimicking the differentiated state of the pregnant gland. Docosapentaenoic acid and eicosapentaenoic acid activated the Jak2/Stat5 signaling pathway and induced a functional differentiation with production of beta-casein. Expression of brain type fatty acid binding protein brain type fatty acid binding protein in virgin transgenic mice also resulted in a reduced ratio of n-6/n-3 PUFA, a robust increase in docosapentaenoic acid accumulation, and mammary differentiation. These data indicate a role of mammary derived growth inhibitor related gene for preferential accumulation of n-3 docosapentaenoic acid and eicosapentaenoic acid in the differentiated gland during pregnancy. Thus, alternation of n-6/n-3 fatty acid compositional ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid and eicosapentaenoic acid, is one of the underlying mechanisms of pregnancy-induced mammary differentiation. C1 Long Isl Jewish Med Ctr, Dept Radiat Oncol, New Hyde Pk, NY 11040 USA. Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Feinstein Inst Med Res, Dept Radiat Oncol, New Hyde Pk, NY 11042 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Shi, YE (reprint author), Long Isl Jewish Med Ctr, Dept Radiat Oncol, New Hyde Pk, NY 11040 USA. EM eshi@lij.edu FU NCI NIH HHS [CA93542-2] NR 49 TC 19 Z9 19 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 IS 13 BP 3351 EP 3362 DI 10.1111/j.1742-4658.2007.05869.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 184SH UT WOS:000247661800014 PM 17547694 ER PT J AU McCormick, BA AF McCormick, Beth A. TI Bacterial-induced hepoxilin A(3) secretion as a pro-inflammatory mediator SO FEBS JOURNAL LA English DT Review DE arachidonic acid; chemotaxis; eicosanoid; hepoxolin A(3); inflammation; intestine; lung; neutrophils; Pseudomonas aeruginosa; Salmonella typhimurium ID HUMAN NEUTROPHILS; SALMONELLA-TYPHIMURIUM; INTESTINAL EPITHELIA; BIOLOGICAL IMPLICATIONS; INTRACELLULAR CALCIUM; PHOSPHOLIPASE A(2); ARACHIDONIC-ACID; MIGRATION; 15-LIPOXYGENASES; TRANSMIGRATION AB Bacterial infections at epithelial surfaces, such as those that line the gut and the lung, stimulate the migration of neutrophils through the co-ordinated actions of chemoattractants secreted from pathogen-stimulated epithelial cells. One such factor involved in attracting polymorphonuclear leukocytes across the epithelium and into the lumen has until recently remained elusive. In 2004, we identified the eicosanoid, hepoxilin A(3), to be selectively secreted from the apical surface of human intestinal or lung epithelial cells stimulated with Salmonella enterica serotype Typhimurium or Pseudomonas aeruginosa, respectively. In this role, the function of hepoxilin A(3) is to guide neutrophils, via the establishment of a gradient, across the epithelial tight junction complex. Interestingly, interruption of the synthetic pathway of hepoxilin A(3) blocks the apical release of hepoxilin A(3) in vitro and the transmigration of neutrophils induced by S. typhimurium both in in vitro and in vivo models of inflammation. Such results have led to the discovery of a completely novel pathway that is not only critical for responses to bacterial pathogens but also has broad implications for inflammatory responses affecting mucosal surfaces in general. Thus, the objective of this review was to highlight the recent findings that implicate hepoxilin A(3) as a key regulator of mucosal inflammation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Charlestown, MA 02129 USA. RP McCormick, BA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Gastroenterol, CNY 114 16th St 114-3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK56754] NR 31 TC 25 Z9 25 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 IS 14 BP 3513 EP 3518 DI 10.1111/j.1742-4658.2007.05911.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188FN UT WOS:000247904900004 PM 17608718 ER PT J AU Weksberg, R Shuman, C Wilkins-Haug, L Mann, M Croughan, M Stewart, D Rakowsky, C Leader, A Hall, J Friedman, JM Simpson, JL Holmes, L Infante-Rivard, C AF Weksberg, Rosanna Shuman, Cheryl Wilkins-Haug, Louise Mann, Mellissa Croughan, Mary Stewart, Donna Rakowsky, Catherine Leader, Arthur Hall, Judith Friedman, J. M. Simpson, Joe Leigh Holmes, Lewis Infante-Rivard, Claire TI Workshop report: evaluation of genetic and epigenetic risks associated with assisted reproductive technologies and infertility SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT Workshop on Evaluation of Genetic and Epidenetic Risks Associated with Reproductive Technologies and Infertility CY JAN 14-15, 2005 CL Toronto, CANADA SP Canadian Inst Hlth Res, Inst Genet & Canc Res, Natl Canc Inst Canadan, Natl Inst Child Hlth & Human Dev, Reproduct Sci Branch ID BECKWITH-WIEDEMANN-SYNDROME; IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; IMPRINTING DEFECTS; ANGELMAN-SYNDROME; INCREASE; OUTCOMES; COUPLES; BORN; ICSI AB In January 2005, the Assisted Reproductive Technologies (ART) Workshop: Evaluation of Genetic and Epigenetic Risks Associated with Assisted Reproductive Technologies and Infertility was convened to evaluate current date on genetic and epigenetic risks to offspring conceived after a period of infertility and/or via ARTs. Formal presentations and workshop breakout groups reviewed the information from a broad range of disciplines and discussed issues regarding study design, molecular approaches, animal model systems, clinical outcomes, and ethical, legal, and psychosocial issues. The key recommendations of the workshop are that: [1] ART research and education should flow from clinical and basic science studies of the fundamental biology of early mammalian embryonic development, with a focus on how infertility and/or ART might disrupt such processes; [2] such research should include the emerging area of epigenetics and its potential role in reproductive health outcomes; [3] methods for the standardization of data collection and for handling and analysis should be employed, including precise definitions of obstetric and perinatal terminology; [4] much greater awareness and ongoing evaluation of the psychosocial impact of ART and ART research on women, their partners, and their offspring are required; and [5] effective methods of knowledge transfer need to be developed and delivered to healthcare providers and to the general public regarding reproductive planning, infertility, and ART, including the potential risks associated with each. C1 Hosp Sick Children, Dept Paediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Univ Western Ontario, Dept Obstet & Gynecol, London, ON, Canada. Univ Western Ontario, Dept Biochem, London, ON, Canada. Childrens Hlth Res Inst, London, ON, Canada. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Hlth Network, Dept Womens Hlth, Toronto, ON, Canada. Univ Toronto, Dept Womens Hlth, Toronto, ON, Canada. Univ Ottawa, Dept Obstet Gynecol & Med, Div Reprod Med, Ottawa, ON, Canada. Univ British Columbia, Dept Paediat, Vancouver, BC, Canada. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Med, Houston, TX 77030 USA. MassGen Hosp Children, Dept Genet, Boston, MA USA. MassGen Hosp Children, Teratol Unit, Boston, MA USA. McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. McGill Univ, Dept Biostat, Montreal, PQ, Canada. RP Weksberg, R (reprint author), Hosp Sick Children, Dept Paediat, Div Clin & Metab Genet, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM rosanna.weksberg@sickkids.ca RI Stewart, Donna Eileen/J-2844-2016; OI Stewart, Donna Eileen/0000-0002-8157-7746; Mann, Mellissa/0000-0002-8075-3824 NR 11 TC 3 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2007 VL 88 IS 1 BP 27 EP 31 DI 10.1016/j.fertnstert.2006.11.114 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 190JC UT WOS:000248054100004 PM 17442312 ER PT J AU Evans, WS Taylor, AE Boyd, DG Johnson, ML Matt, DW Jimenez, Y Nestler, JE AF Evans, William S. Taylor, Ann E. Boyd, David G. Johnson, Michael L. Matt, Dennis W. Jimenez, Yarisie Nestler, John E. TI Lack of effect of short-term diazoxide administration on luteinizing hormone secretion in women with polycystic ovary syndrome SO FERTILITY AND STERILITY LA English DT Article DE PCOS; LH secretion; hyperinsulinemia; diazoxide ID GONADOTROPIN-SECRETION; BINDING GLOBULIN; MENSTRUAL-CYCLE; INSULIN; DISEASE; SUPPRESSION; SERUM; LH AB Objective: To test the hypothesis that an acute reduction in circulating insulin affects LH secretion in women with polycystic ovary syndrome (PCOS). Design: Prospective study in normal and PCOS women. Setting: General Clinic Research Centers at the University of Virginia, the Medical College of Virginia and the Massachusetts General Hospital. Patient(s): Six normal women and five women with PCOS. Intervention(s): Administration of diazoxide to lower circulating insulin concentrations. Main Outcome Measure(s): Characteristics of LH secretion as appraised by multiparameter deconvolution and estimation of approximate entropy. Result(s): Short-term administration of diazoxide had no effect on the secretion of LH in women with PCOS. Conclusion(s): Hyperinsulinemia resulting from insulin resistance in women with PCOS may not have a direct effect on gonadotropin secretion. C1 Univ Virginia, Dept Med, Natl Sci Fdn Ctr Biol Timing, Charlottesville, VA USA. Univ Virginia, Dept Obstet & Gynecol, Natl Sci Fdn Ctr Biol Timing, Charlottesville, VA USA. Univ Virginia, Ctr Biomath Technol, Charlottesville, VA USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Univ Virginia, Dept Med, Charlottesville, VA USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Obstet & Gynecol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Richmond, VA 23298 USA. RP Evans, WS (reprint author), Univ Virginia Hlth Syst, Box 800404, Charlottesville, VA 22908 USA. EM wse2p@virginia.edu FU NCRR NIH HHS [RR-00847, R01 RR019991-04, RR-00065, R01 RR019991-05, RR-01066, R01 RR019991]; NICHD NIH HHS [R01 HD035629, U54 HD-29164, R03-HD 35251, R01HD36529, R29-HD-33509]; NIDDK NIH HHS [R25 DK064122-04, R25 DK064122] NR 21 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2007 VL 88 IS 1 BP 118 EP 124 DI 10.1016/j.fertnstert.2006.11.109 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 190JC UT WOS:000248054100018 PM 17289040 ER PT J AU Moskowitz, MA AF Moskowitz, Michael A. TI Genes, proteases, cortical spreading depression and migraine: Impact on pathophysiology and treatment SO FUNCTIONAL NEUROLOGY LA English DT Article DE ion channel; migraine; neurogenic inflammation; pathophysiology; spreading depression; trigeminal nerve. ID FAMILIAL HEMIPLEGIC MIGRAINE; TRANSCRANIAL MAGNETIC STIMULATION; VASCULAR HEAD PAIN; EVOKED-POTENTIALS; EPISODIC ATAXIA; CEREBRAL-CORTEX; FUNCTIONAL MRI; BRAIN; AURA; MECHANISMS AB Migraine headaches have a complex pathophysiology; both vascular and neuronal mechanisms have been proposed. One possible scenario begins with a series of destabilising events within the brain that trigger cortical spreading depression (CSD). CSD can cause both migraine aura and trigeminal activation which, in turn, promotes neuropeptide release and triggers peripheral and central mechanisms that promote headache and autonomic activation. Susceptibility to CSD and to migraine is, in part, genetically determined. The best evidence to date comes from certain subtypes of migraine with aura in which point mutations in genes controlling translocation of calcium, sodium and potassium have been implicated. This review briefly summarises recent migraine research that supports CSD as an upstream driver of the migraine attack as well as an activator of the trigemino-vascular system. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. EM moskowitz@helix.mgh.harvard.edu NR 47 TC 41 Z9 44 U1 1 U2 2 PU C I C-EDIZIONI INT SRL PI ROME PA CORSO TRIESTE, 42, 00198 ROME, ITALY SN 0393-5264 J9 FUNCT NEUROL JI Funct. Neurol. PD JUL-SEP PY 2007 VL 22 IS 3 BP 133 EP 136 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 226SW UT WOS:000250609800002 PM 17925161 ER PT J AU Kim, AY AF Kim, Arthur Y. TI Early antiretroviral therapy: an immunotherapy to combat HCV in HIV-1/HCV coinfection SO FUTURE VIROLOGY LA English DT Editorial Material ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER-RELATED DEATHS; CD8(+) T-CELLS; IMMUNE-RESPONSES; HIV; INFECTION; PERSISTENCE; PROTECTION; FIBROSIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Boston, MA USA. RP Kim, AY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Boston, MA USA. EM akim1@partners.org NR 20 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 J9 FUTURE VIROL JI Future Virol. PD JUL PY 2007 VL 2 IS 4 BP 319 EP 323 DI 10.2217/17460794.2.4.319 PG 5 WC Virology SC Virology GA 209ZT UT WOS:000249427200002 ER PT J AU Rodriguez, JR Salvia, R Crippa, S Warshaw, AL Bassi, C Falconi, M Thayer, SP Lauwers, GY Capelli, P Mino-Kenudson, M Razo, O Mcgrath, D Pederzoli, P Castillo, CFD AF Rodriguez, J. Ruben Salvia, Roberto Crippa, Stefano Warshaw, Andrew L. Bassi, Claudio Falconi, Massimo Thayer, Sarah P. Lauwers, Gregory Y. Capelli, Paola Mino-Kenudson, Mari Razo, Oswaldo Mcgrath, Deborah Pederzoli, Paolo Castillo, Carlos Fernandez-Del TI Branch-duct intraductal papillary mucinous neoplasms: Observations in 145 patients who underwent resection SO GASTROENTEROLOGY LA English DT Article ID FOLLOW-UP; SURGICAL-MANAGEMENT; MAIN-DUCT; PANCREAS; TUMORS; DIFFERENTIATION; MALIGNANCY; FEATURES AB Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas arising in branch ducts are thought to be less aggressive than their main-duct counterparts, and guidelines for their conservative management were recently proposed. This study describes the combined experience of 2 tertiary centers with branch-duct IPMNs aiming to validate these recommendations. Methods: A review of 145 patients with resected, pathologically confirmed, branch-duct IPMNs between 1996 and 2005 was conducted. Results: Sixty-six patients (45.5%) had adenoma, 47 (32%) borderline tumors, 16 (11%) carcinoma in situ, and 16 (11%) invasive carcinoma. Median age was similar between benign and malignant subgroups (66 vs 67.5 years, respectively). jaundice was more frequent in patients with cancer (12.5% vs 1.8%, respectively, P =.022) and abdominal pain in patients with benign tumors (45% vs 25%, respectively, P =.025). Forty percent of tumors were discovered incidentally. Findings associated with malignancy were the presence of a thick wall (P <.001), nodules (P <.001), and tumor diameter >= 30 mm (P <.001). All neoplasms with cancer were larger than 30 mm in size or had nodules or caused symptoms. After a mean follow-up of 45 months, the 5-year disease-specific survival for branch-duct IPMNs with noninvasive neoplasms was 100% and, for invasive cancer, was 63%. Conclusions: This large cohort of resected branch-duct IPMNs shows that cancer is present in 22% of cases and validates the recent guidelines that indicate absence of malignancy in tumors < 30 mm, without symptoms or mural nodules. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Univ Verona, Dept Surg, Verona, Italy. Univ Verona, Dept Surg, I-37100 Verona, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Verona, Dept Pathol, I-37100 Verona, Italy. RP Castillo, CFD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, WACC 336,15 Parkman St, Boston, MA 02114 USA. EM CFERNANDEZ@PARTNERS.ORG FU NIDDK NIH HHS [K08 DK071329] NR 26 TC 232 Z9 235 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2007 VL 133 IS 1 BP 72 EP 79 DI 10.1053/j.gastro.2007.05.010 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190JP UT WOS:000248055400014 PM 17631133 ER PT J AU Sugimoto, K Ogawa, A Shimomura, Y Nagahama, K Mizoguchi, A Bhan, AK AF Sugimoto, Ken Ogawa, Atsuhiro Shimomura, Yasuyo Nagahama, Kiyotaka Mizoguchi, Atsushi Bhan, Atul K. TI Inducible IL-12-Producing B cells regulate Th2-mediated intestinal inflammation SO GASTROENTEROLOGY LA English DT Article ID ALPHA MUTANT MICE; T-CELLS; AUTOIMMUNE INFLAMMATION; EXPERIMENTAL COLITIS; BOWEL-DISEASE; LUPUS MICE; CYTOKINE; IL-12; INTERLEUKIN-12; IL-23 AB Background & Aims: Our previous studies have identified a B-cell subset that is induced under inflammatory conditions in T-cell receptor alpha knockout (TCR alpha KO) mice and contributes to the attenuation of colitis by producing interleukin (IL)-10. However, it is unclear whether IL-10-producing B cells directly or indirectly regulate inflammation. Methods: Cytokine production of purified mesenteric lymph node (MLN) B cells was examined by flow cytometric analysis, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and RNase protection assay. To investigate the functional role of IL-12p70 in the pathogenesis of colitis in TCR alpha KO mice, IL-12p35-deficient TCR alpha double knockout mice were generated. Results: In the absence of B cells or IL-10, IL-12p35 expression was significantly down-regulated in the MLN of TCR alpha KO mice. The expression of IL-12p35 was restored in the recipient B-cell-deficient TCR alpha double knockout (alpha mu DKO) mice by the transfer of B cells capable of producing IL-10. Notably, B cells predominantly produced IL-12p35 in the MLN through the help of IL-10-producing B cells. Functionally, IL-12 is involved in the regulation of the T-helper (Th) 2-mediated inflammation as indicated by the development of much more severe colitis in IL-12p35-deficient TCR alpha double knockout (alpha p35DKO) mice compared with TCR alpha KO mice. In addition, transfer of MLN B cells from TCR alpha KO mice but not from alpha p35DKO mice suppressed colitis in recipient alpha mu DKO mice. Conclusions: These studies have identified a novel IL-12-producing regulatory B-cell subset that develops under Th2-mediated intestinal inflammatory conditions and in the presence of IL-10 and is involved in the regulation of intestinal inflammation. C1 Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM abhan@partners.org FU NIDDK NIH HHS [DK43351, DK64351, DK47677] NR 47 TC 36 Z9 38 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2007 VL 133 IS 1 BP 124 EP 136 DI 10.1053/j.gastro.2007.03.112 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190JP UT WOS:000248055400018 PM 17631137 ER PT J AU Rattner, DW Hawes, R AF Rattner, David W. Hawes, Robert TI What is NOSCAR? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org NR 2 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2007 VL 66 IS 1 BP 11 EP 12 DI 10.1016/j.gie.2007.05.015 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190KB UT WOS:000248056600003 PM 17591467 ER PT J AU Yusuf, TE Tsutaki, S Wagh, MS Waxman, I Brugge, WR AF Yusuf, Tony E. Tsutaki, Shinichi Wagh, Mihir S. Waxman, Irving Brugge, William R. TI The EUS hardware store: state of the art technical review of instruments and equipment (with videos) SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID ENDOSCOPIC ULTRASONOGRAPHY; SCANNING ECHOENDOSCOPE; GI TRACT; CARCINOMA; DIAGNOSIS; DISEASES; LESIONS; CANCER; PANCREATITIS; INVOLVEMENT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Olympus Med Syst Corp, Endoscope R&D Dept, Tokyo, Japan. Univ Chicago Hosp, Div Gastroenterol & Hepatol, Chicago, IL 60637 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. NR 30 TC 12 Z9 12 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2007 VL 66 IS 1 BP 131 EP 143 DI 10.1016/j.gie.2006.03.935 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190KB UT WOS:000248056600028 PM 17591487 ER PT J AU Palomeque, J Chemaly, ER Colosi, P Wellman, JA Zhou, S del Monte, F Hajjar, RJ AF Palomeque, J. Chemaly, E. R. Colosi, P. Wellman, J. A. Zhou, S. del Monte, F. Hajjar, R. J. TI Efficiency of eight different AAV serotypes in transducing rat myocardium in vivo SO GENE THERAPY LA English DT Article DE gene transfer; AAV vectors; cardiovascular gene therapy ID RECOMBINANT ADENOASSOCIATED VIRUS; GENE-THERAPY VECTORS; HEART-FAILURE; SKELETAL-MUSCLE; IMMUNE-RESPONSES; VIRAL VECTOR; TYPE-2; ADENOVIRUS; DELIVERY; EXPRESSION AB Recombinant adeno-associated (AAV) viruses have unique properties, which make them ideal vectors for gene transfer targeting the myocardium. Numerous serotypes of AAV have been identified with variable tropisms towards cardiac tissue. In the present study, we investigated the time course of expression of eight different AAV serotypes in rat myocardium and the nature of the immunity against these serotypes. We first assessed whether neutralizing antibodies (NAb) were present for any of the serotype in the rats. We injected 100 mu l of each AAV 1-8 serotype (10(12) DNAse resistant particles/ml), encoding LacZ gene, into the apical wall of rat myocardium. At 1, 4, 12 and 24 weeks after gene delivery, the animals were killed and beta-galactosidase (beta-gal) activity was assessed by luminometry. Additionally, LacZ genomic copies and AAV capsids copies were measured through standard polymerase chain reaction analysis and cryosections from the area of viral injection were stained for X-gal detection at the same time points. No NAbs were detected against any of AAV serotypes. At all the time points studied, AAV1, 6 and 8 demonstrated the highest efficiency in transducing rat hearts in vivo. Parallel to the results with beta-gal activity, the highest levels LacZ and AAV DNA genomic copies were with AAV1, 6 and 8. The positive X-gal staining depicted by these serotypes confirmed these results. These results indicate that among the various AAV serotypes, AAV1, 6 and 8 have differential tropism for the heart unaffected by pre-existing NAb in the rat. Although AAV 1 and 6 vectors induced rapid and robust expression and reach a plateau at 4 weeks, AAV 8 continued increasing until the end of the study. AAV 2, 5 and 7 vectors were slower to induce expression of the reporter gene, but did reach levels of expression comparable to AAV1 and AAV6 vectors after 3 months. C1 Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Sch Med, Charlestown, MA 02129 USA. Avigen Inc, Alameda, CA USA. RP Hajjar, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Sch Med, Bldg 149,13th St,4 Floor,CNY-4, Charlestown, MA 02129 USA. EM rhajjar@partners.org FU NHLBI NIH HHS [HL71763, HL 078691, HL 080498, HL 57263] NR 49 TC 61 Z9 66 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 2007 VL 14 IS 13 BP 989 EP 997 DI 10.1038/sj.gt.3302895 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 181VC UT WOS:000247463200001 PM 17251988 ER PT J AU Jeong, KH Bakowska, JC Song, IO Fu, N Breakefield, XO Kaiser, UB AF Jeong, K-H Bakowska, J. C. Song, I. O. Fu, N. Breakefield, X. O. Kaiser, U. B. TI Improvement in reproductive parameters in hypogonadal female mice by regulated gene replacement therapy in the central nervous system SO GENE THERAPY LA English DT Article DE herpes simplex virus-1; gene replacement; central nervous system; hypogonadism; gonadotropin-releasing hormone; gonadotropin ID GONADOTROPIN-RELEASING-HORMONE; PROTEIN-COUPLED RECEPTOR; AREA BRAIN GRAFTS; INFECTIOUS DELIVERY; AMPLICON VECTORS; PREOPTIC AREA; TRANSGENE EXPRESSION; PARKINSONS-DISEASE; LENTIVIRAL VECTORS; KISS-1 PEPTIDE AB One of the challenges of gene targeting is to achieve regulated transgene expression in specific target cells. The hypogonadal (hpg) mice are genetically deficient in hypothalamic gonadotropin-releasing hormone (GnRH) production due to a deletion in the GnRH gene, resulting in hypogonadotropic hypogonadism. Here we show an improvement in reproductive parameters of adult female homozygous hpg mice by direct infusion into the hypothalamic preoptic area (POA) of a herpes simplex virus (HSV)-based amplicon vector containing a 13.5 kb genomic fragment encoding the GnRH gene together with its cognate promoter and regulatory elements. Following vector injection, GnRH-expressing neurons were detected in the POA, and pituitary and plasma gonadotropin levels as well as ovarian and uterine weights increased. In addition, a subset of injected hpg mice demonstrated cyclic estrous changes, consistent with regulated control of GnRH production. Administration of kisspeptin-10 resulted in an increase in plasma luteinizing hormone levels, further supporting appropriate regulation of the introduced GnRH transgene. These findings indicate that delivery of the GnRH gene resulted in selective neuronal expression of GnRH and regulated hypothalamic GnRH release. To our knowledge, this is the first example of the correct targeting of a gene under its cognate promoter to neurons resulting in selective and regulated synthesis of a biologically active peptide, and thus may have a wide range of applications in the treatment of human disorders. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit,Dept Neurol, Charlestown, MA USA. RP Kaiser, UB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Dept Med, 221 Longwood ave, Boston, MA 02115 USA. EM ukaiser@partners.org FU NICHD NIH HHS [U54-HD28934, U54-HD28138, R21-HD050412]; NINDS NIH HHS [NS24279] NR 50 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 2007 VL 14 IS 14 BP 1092 EP 1101 DI 10.1038/sj.gt.3302957 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 185NR UT WOS:000247718200004 PM 17476303 ER PT J AU Yeager, DE Magruder, KM Knapp, RG Nicholas, JS Frueh, BC AF Yeager, Derik E. Magruder, Kathryn M. Knapp, Rebecca G. Nicholas, Joyce S. Frueh, B. Christopher TI Performance characteristics of the Posttraumatic Stress Disorder Checklist and SPAN in Veterans Affairs primary care settings SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE PCL; posttraumatic stress disorder; SPAN; screening; primary care ID PTSD CHECKLIST; FEMALE VETERANS; EPIDEMIOLOGY; CLINICS; VALIDATION; SYMPTOMS; VALIDITY; HEALTH AB Background: Posttraumatic stress disorder (PTSD) is a treatable disorder, and individuals with this condition may benefit from early detection. Many people with PTSD are not aware of its symptoms and do not seek treatment, making a brief and targeted screening program a worthwhile endeavor. For this reason, research aimed at improving screening instruments could yield substantial benefits. Objectives: The primary objective of this research was to assess the diagnostic performance of two popular PTSD screening assessments, the PTSD Checklist (PCL) and the SPAN, in a Veterans Affairs (VA) primary care setting. Additionally, we compared the screening performance of these two assessments by sex and race. Methods: The PCL and SPAN were compared with a gold standard, the Clinician-Administered PTSD Scale. Receiver operating characteristic curves were used in conjunction with sensitivity and specificity measures to assess the performance of each screening assessment. These analyses are based on a large database (it = 1076) that was derived from a multisite cross-sectional study conducted at four southeastern VA medical centers. Results: Results for the PCL support cutoff scores lower than those previously published, whereas results for the SPAN support the previously recommended cutoff score of 5 (sensitivity of 73.68% and specificity of 81.99%). We found no significant difference in areas under the curve (AUCs) by sex and by race between the PCL and SPAN. We did find that there was a highly significant difference (P <.0006) in overall diagnostic ability (as measured by the AUC) between the PCL (AUC=0.882) and SPAN (AUC=0.837), making the PCL the preferred screening tool, unless brevity is essential. Conclusions: Clinicians and researchers should consider lower cutoff scores for the PCL, but the originally suggested cutoff score for the SPAN is appropriate. Published by Elsevier Inc. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29452 USA. RP Magruder, KM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM magrudkm@musc.edu NR 28 TC 68 Z9 68 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2007 VL 29 IS 4 BP 294 EP 301 DI 10.1016/j.genhosppsych.2007.03.004 PG 8 WC Psychiatry SC Psychiatry GA 188CM UT WOS:000247896400002 PM 17591505 ER PT J AU De Jager, PL Franchimont, D Waliszewska, A Bitton, A Cohen, A Langelier, D Belaiche, J Vermeire, S Farwell, L Goris, A Libioulle, C Jani, N Dassopoulos, T Bromfield, GP Dubois, B Cho, JH Brant, SR Duerr, RH Yang, H Rotter, JI Silverberg, MS Steinhart, AH Daly, MJ Podolsky, DK Louis, E Hafler, DA Rioux, JD AF De Jager, P. L. Franchimont, D. Waliszewska, A. Bitton, A. Cohen, A. Langelier, D. Belaiche, J. Vermeire, S. Farwell, L. Goris, A. Libioulle, C. Jani, N. Dassopoulos, T. Bromfield, G. P. Dubois, B. Cho, J. H. Brant, S. R. Duerr, R. H. Yang, H. Rotter, J. I. Silverberg, M. S. Steinhart, A. H. Daly, M. J. Podolsky, D. K. Louis, E. Hafler, D. A. Rioux, J. D. CA Quebec IBD Genetics Consortium NIDDK IBD Genetics Consortium TI The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases SO GENES AND IMMUNITY LA English DT Article DE Toll-like receptor; inflammatory bowel disease; NFKB1; TLR4; TIRAP ID NFKB1 PROMOTER POLYMORPHISM; EX-VIVO RESPONSE; CROHNS-DISEASE; ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; ASP299GLY POLYMORPHISM; GENETIC ASSOCIATION; HAPLOTYPE STRUCTURE; AUTOIMMUNE-DISEASE; IN-VIVO AB The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15 - 1.48; P = 0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16 - 1.54; P = 0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04 - 1.30; P = 0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. McGill Univ, Montreal Gen Hosp, Dept Internal Med, Div Gastroenterol, Montreal, PQ H3G 1A4, Canada. McGill Univ, Ctr Hlth, Div Gastroenterol, Montreal, PQ H3G 1A4, Canada. McGill Univ, Jewish Gen Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada. CHU Sherbrooke, Hop Fleurimont, Sherbrooke, PQ J1H 5N4, Canada. Univ Liege, CHU, Div Gastroenterol, B-4000 Liege, Belgium. Univ Hosp Gasthuisberg, Div Gastroenterol, B-3000 Louvain, Belgium. Univ Louvain, Sect Expt Neurol, B-3001 Louvain, Belgium. Univ Liege, Ctr Biomed Integrat Genoproteom, B-4000 Liege, Belgium. Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. Johns Hopkins Univ, Harvey M & Lyn P Meyeroff Inflammatory Bowel Dis, Dept Med, Baltimore, MD 21218 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Yale Univ, IBD Ctr, Dept Med, Gastroenterol Sect, New Haven, CT 06520 USA. Yale Univ, IBD Ctr, Dept Genet, Gastroenterol Sect, New Haven, CT 06520 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. Cedars Sinai Med Ctr, Steven Spielberg Pediat Res Ctr, Dept Med, Div Med Genet, Los Angeles, CA 90048 USA. Univ Toronto, Mt Sinai Hosp, IBD Ctr, Div Gastroenterol, Toronto, ON, Canada. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Montreal, Montreal Heart Inst, Montreal, PQ H3C 3J7, Canada. RP Rioux, JD (reprint author), Univ Montreal, Montreal Heart Inst, 5000 Belanger St,Rm S-6400, Montreal, PQ H1T 1C8, Canada. EM rioux@broad.mit.edu RI Silverberg, Mark/B-4183-2008; Goris, An/F-2943-2010; Rioux, John/A-9599-2015; OI Goris, An/0000-0002-1276-6682; Rioux, John/0000-0001-7560-8326; Duerr, Richard/0000-0001-6586-3905; Vermeire, Severine/0000-0001-9942-3019 FU NIDDK NIH HHS [U01 DK062420] NR 63 TC 95 Z9 98 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUL PY 2007 VL 8 IS 5 BP 387 EP 397 DI 10.1038/sj.gene.6364398 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 195EB UT WOS:000248394200003 PM 17538633 ER PT J AU French, CA Groszer, M Preece, C Coupe, AM Rajewsky, K Fisher, SE AF French, Catherine A. Groszer, Matthias Preece, Christopher Coupe, Anne-Marie Rajewsky, Klaus Fisher, Simon E. TI Generation of mice with a conditional Foxp2 null allele SO GENESIS LA English DT Article DE Foxp2; conditional null allele; Sox2-Cre; speech and language; brain development ID LANGUAGE DISORDER; TRANSCRIPTIONAL REPRESSORS; GENE-EXPRESSION; SEVERE SPEECH; BRAIN; DISRUPTION; EVOLUTION AB Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12-14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain. We demonstrate that early global Cre-mediated recombination yields a null allele, as shown by loss of the IoxP-flanked exons at the RNA level and an absence of Foxp2 protein. Homozygous null mice display severe motor impairment, cerebellar abnormalities and early postnatal lethality, consistent with other Foxp2 mutants. When crossed to transgenic lines expressing Cre protein in a spatially and/or temporally controlled manner, these conditional mice will provide new insights into the contributions of Foxp2 to distinct neural circuits, and allow dissection of roles during development and in the mature brain. C1 Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP French, CA (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. EM simon.fisher@wetl.ox.ac.uk RI Fisher, Simon/E-9130-2012; OI Fisher, Simon/0000-0002-3132-1996; French, Catherine/0000-0003-2072-8413 FU Wellcome Trust NR 31 TC 48 Z9 48 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD JUL PY 2007 VL 45 IS 7 BP 440 EP 446 DI 10.1002/dvg.20305 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 197EF UT WOS:000248536700003 PM 17619227 ER PT J AU Dickson, MR Go, RCP Wiener, H Blacker, D Bassett, SS AF Dickson, M. R. Go, R. C. P. Wiener, H. Blacker, D. Bassett, S. S. TI A genomic scan for age at onset of Alzheimer's disease from the NIMH genetic initiative SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Univ Alabama, Dept Epi, Birmingham, AL USA. Massachusetts Gen Hosp, Dept Epi, Boston, MA 02114 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 469 EP 470 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700077 ER PT J AU Dupuis, J Manning, A Cho, K Cupples, LA Meigs, JB Karasik, D Kiel, DP Siegmund, D AF Dupuis, J. Manning, A. Cho, K. Cupples, L. A. Meigs, J. B. Karasik, D. Kiel, D. P. Siegmund, D. TI Application of robust score statistics to quantitative trait linkage analysis in the Framingham Heart Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 470 EP 471 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700080 ER PT J AU Wang, W Niendorf, KB Patel, D Marroni, F Parmigiani, G Tsao, H AF Wang, W. Niendorf, K. B. Patel, D. Marroni, F. Parmigiani, G. Tsao, H. TI Predicting germline p16 mutational status within melanoma families using MELAPRO SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 503 EP 503 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700194 ER PT J AU Hoffman, KE Horowitz, NS Russell, AH AF Hoffman, Karen E. Horowitz, Neil S. Russell, Anthony H. TI Healing of vulvo-vaginal radionecrosis following revascularization SO GYNECOLOGIC ONCOLOGY LA English DT Article DE radiation therapy; radiation injury; vaginal cancer; vulvar cancer ID SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; CERVICAL-CANCER; SMOKING; DISEASE; IRRADIATION; SURVIVAL; INJURY AB Background. Invasive cancers of the vagina and vulva are treated with radiation-based therapy when proximity of the bladder and/or rectum precludes conservative surgical resection. Patient factors affect non-malignant tissue tolerance to radiation exposure. Case. A smoker with atherosclerotic disease developed tissue necrosis and the worsening of claudication after chemoradiation treatment of locally advanced squamous cell carcinoma of the vulva and vagina. Healing occurred after surgical revascularization. Conclusion. Conditions with impaired microvasculature, such as smoking and atherosclerotic disease, are associated with an increased incidence and severity of complications after radiation treatment. Patients undergoing pelvic radiation treatment should be counseled to modify their vascular risk factors. If this fails and patients develop significant radiation necrosis due to compromised arteriole flow, revascularization or stenting may offer important treatment options. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. RP Hoffman, KE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM khoffman1@partners.org NR 13 TC 3 Z9 3 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2007 VL 106 IS 1 BP 262 EP 264 DI 10.1016/j.ygyno.2007.03.038 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 183LW UT WOS:000247575300042 PM 17507081 ER PT J AU Doshi, JA Polsky, D Chang, VW AF Doshi, Jalpa A. Polsky, Daniel Chang, Virginia W. TI Prevalence and trends in obesity among aged and disabled US Medicare beneficiaries, 1997-2002 SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; BARIATRIC SURGERY; OVERWEIGHT; COSTS; DISEASE; ADULTS AB Given Medicare's recent national coverage decision on bariatric surgery, as well as potential coverage expansions for other obesity-related treatments, data on obesity in the Medicare population have great relevance. Using nationally representative data, we estimate that. between 1997 and 2002, the prevalence of obesity in the Medicare population increased by 5.6 percentage points, or about 2.7 million beneficiaries. By 2002, 21.4 percent of aged beneficiaries and 39.3 percent of disabled beneficiaries were obese, compared with 16.4 percent and 32.5 percent, respectively, in 1997. Using 2002 data, we estimate that three million beneficiaries would be eligible for bariatric surgery coverage under current Medicare policy. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Doshi, JA (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. EM jdoshi@mail.med.upenn.edu FU NIA NIH HHS [R01-AG024451, R01 AG024451]; NICHD NIH HHS [K12-HD043459, K12 HD043459] NR 18 TC 17 Z9 17 U1 1 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2007 VL 26 IS 4 BP 1111 EP 1117 DI 10.1377/hlthaff.26.4.1111 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 191GL UT WOS:000248119500024 PM 17630454 ER PT J AU Micheyl, C Carlyon, RP Gutschalk, A Melcher, JR Oxenham, AJ Rauschecker, JP Tian, B Wilson, EC AF Micheyl, Christophe Carlyon, Robert P. Gutschalk, Alexander Melcher, Jennifer R. Oxenham, Andrew J. Rauschecker, Josef P. Tian, Biao Wilson, E. Courtenay TI The role of auditory cortex in the formation of auditory streams SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT Conference on Auditory Cortex - Listening Brain CY SEP, 2006 CL Nottingham, ENGLAND SP MIC Inst Hearing Res DE auditory cortex; auditory scene analysis; single-unit recordings; magnetoencephalography; functional magnetic resonance imaging ID STARLINGS STURNUS-VULGARIS; GOLDFISH CARASSIUS-AURATUS; MIDDLE LATENCY COMPONENTS; TONE SEQUENCES; SCENE ANALYSIS; PERCEPTUAL ORGANIZATION; FUNDAMENTAL-FREQUENCY; SONGBIRD FOREBRAIN; EVOKED-POTENTIALS; TIME INTERVALS AB Auditory streaming refers to the perceptual parsing of acoustic sequences into "streams", which makes it possible for a listener to follow the sounds from a given source amidst other sounds. Streaming is currently regarded as an important function of the auditory system in both humans and animals, crucial for survival in environments that typically contain multiple sound sources. This article reviews recent findings concerning the possible neural mechanisms behind this perceptual phenomenon at the level of the auditory cortex. The first part is devoted to intra-cortical recordings, which provide insight into the neural "micromechanisms" of auditory streaming in the primary auditory cortex (A1). In the second part, recent results obtained using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in humans, which suggest a contribution from cortical areas other than A1, are presented. Overall, the findings concur to demonstrate that many important features of sequential streaming can be explained relatively simply based on neural responses in the auditory cortex. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MRC, Cognit & Brain Sci Unit, Cambridge, England. Univ Heidelberg, Dept Neurol, D-6900 Heidelberg, Germany. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Georgetown Inst Cognit & Computat Sci, Washington, DC 20007 USA. Harvard Univ, MIT, Speech & Hearing Biosci & Technol Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Micheyl, C (reprint author), Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. EM cmicheyl@umn.edu RI Carlyon, Robert/A-5387-2010; Rauschecker, Josef/A-4120-2013; OI Carlyon, Robert/0000-0002-6166-501X; Oxenham, Andrew/0000-0002-9365-1157 FU Medical Research Council [MC_U105559842]; NIDCD NIH HHS [R01 DC007657-01A1, P01 DC00119, R01 DC003489, R01 DC003489-05, R01 DC005216, R01 DC005216-06, R01 DC007657, R01 DC05216, R01 DC07657]; NINDS NIH HHS [R01 NS052494] NR 88 TC 106 Z9 107 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2007 VL 229 IS 1-2 BP 116 EP 131 DI 10.1016/j.heares.2007.01.007 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 191PI UT WOS:000248143100012 PM 17307315 ER PT J AU Spiegel, BMR Bolus, R Han, S Tong, M Esraitian, E Talley, J Tran, T Karsan, HA Durazo, F Bacon, B Martin, P Younossi, Z Hwa-Ong, S Kanwal, F AF Spiegel, Brennan M. R. Bolus, Roger Han, Steven Tong, Myron Esraitian, Eric Talley, Jennifer Tran, Tram Karsan, Hetal A. Durazo, Francisco Bacon, Bruce Martin, Paul Younossi, Zobair Hwa-Ong, Siew Kanwal, Fasiha TI Development and validation of a disease-targeted quality of life instrument in chronic hepatitis B: The hepatitis B quality of life instrument, version 1.0 SO HEPATOLOGY LA English DT Article AB Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV. the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test-retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test-retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health. Conclusion: Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,CURE Digest Dis Res Ct, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Dept Internal Med, Div Gastroenterol & Hepatol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Internal Med, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA USA. Cedars Sinai Med Ctr, Dept Internal Med, Div Hepatol, Los Angeles, CA 90048 USA. Atlanta Gastroenterol Associates, Atlanta, GA USA. Emory Univ, Sch Med, Dept Internal Med, Div Hepatol, Atlanta, GA 30322 USA. Mt Sinai Sch Med, Dept Internal Med, Div Hepatol, New York, NY USA. Inova Fairfax Hosp, Ctr Liver Dis, Fairfax, VA USA. St Louis Univ, Dept Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Novartis Pharma AG, Basel, Switzerland. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,CURE Digest Dis Res Ct, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU NIDDK NIH HHS [T32 DK07180-30, 2P30 DK 041301-17] NR 9 TC 26 Z9 28 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2007 VL 46 IS 1 BP 113 EP 121 DI 10.1002/hep.21692 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 184JJ UT WOS:000247637000016 PM 17596882 ER PT J AU Aweeka, FT Kang, M Yu, JY Lizak, P Alston, B Chung, RT AF Aweeka, F. T. Kang, M. Yu, J-Y Lizak, P. Alston, B. Chung, R. T. CA AIDS Clin Trials Grp 5092s Study T TI Pharmacokinetic evaluation of the effects of ribavirin on zidovudine triphosphate formation: ACTG 5092s Study Team SO HIV MEDICINE LA English DT Article DE hepatitis C virus treatment; intracellular zidovudine; pharmacokinetics; ribavirin ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC HEPATITIS-C; REVERSE-TRANSCRIPTASE; IN-VITRO; PHOSPHORYLATION; REPLICATION; ANTAGONIZES; ANEMIA AB Objectives Ribavirin (RBV) is used for the treatment of hepatitis C virus (HCV) infection in subjects with HIV-1 infection who may require antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors including zidovudine (ZDV). We sought to investigate the potential antagonism between RBV and ZDV by evaluating the impact of RBV on the formation of intracellular ZDV triphosphate (TP) in HIV-infected patients receiving ZDV who were treated for HCV infection. Methods Serial plasma and intracellular ZDV TP pharmacokinetics (PK) were determined in 14 subjects at entry (within 2 weeks prior to RBV administration) and at 8 weeks following initiation of RBV. Intracellular ZDV TP in peripheral blood mononuclear cells (PBMC) was quantified by a validated cartridge/liquid chromatography/tandem mass spectrometry method. PK exposure was estimated from the steady-state area under the concentration vs time curve (AUC(0-12 h)) in plasma and PBMC. Results Ribavirin did not have a statistically significant impact on ZDV TP AUC(0-12 h), plasma ZDV AUC(0-12 h) or the ratio of ZDV TP AUC(0-12 h) to plasma ZDV AUC(0-12 h), although there was a trend towards an increase post-RBV ratio compared with pre-RBV. There was extensive variability in the ZDV TP AUC(0-12 h). Conclusions Ribavirin did not inhibit formation of ZDV TP in PBMC in 14 patients receiving ZDV as part of ART and RBV-based HCV therapy for 8 weeks. These results are consistent with those of a previously published limited study in seven subjects. These PK findings should be weighed carefully against emerging clinical reports of significant anaemia associated with combination ZDV and high-dose RBV therapy. C1 Univ Calif San Francisco, Drug Res Unit, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Aweeka, FT (reprint author), Univ Calif San Francisco, Drug Res Unit, 521 Parnassus Ave, San Francisco, CA 94143 USA. EM faweeka@sfghsom.ucsf.edu FU NIAID NIH HHS [AI38858] NR 13 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD JUL PY 2007 VL 8 IS 5 BP 288 EP 294 DI 10.1111/j.1468-1293.2007.00472.x PG 7 WC Infectious Diseases SC Infectious Diseases GA 177CB UT WOS:000247130100004 PM 17561874 ER PT J AU Kim, AI Dorn, A Bouajram, R Saab, S AF Kim, A. I. Dorn, A. Bouajram, R. Saab, S. TI The treatment of chronic hepatitis C in HIV-infected patients: a meta-analysis SO HIV MEDICINE LA English DT Article DE hepatitis C; HIV; interferon treatment ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; ANTIRETROVIRAL THERAPY; COINFECTED PATIENTS; CLINICAL-TRIALS; LIVER FIBROSIS; HEPATOCELLULAR-CARCINOMA; MORTALITY; PROGRESSION; CIRRHOSIS AB Objective Hepatitis C virus (HCV) disease progression appears to be accelerated in patients coinfected with HIV. The impact of HCV on coinfected patients is being realized as patients are now living longer. The objective of our study was to further elucidate incremental improvement and safety concerns with combinations of pegylated interferon (peginterferon), interferon and ribavirin based on data obtained from prospective randomized controlled trials. Methods A search of MEDLINE and the Cochrane database for material published between 1966 and 29 August 2005 and a hand search of abstracts from national meetings held between 2001 and August 2005 were performed. Trials comparing the use of peginterferon plus ribavirin vs peginterferon or interferon plus ribavirin were assessed. Results In six randomized controlled trials, 1756 patients were randomized. Sustained virological response was greater for patients treated with peginterferon plus ribavirin compared with patients treated with interferon plus ribavirin [odds ratio (OR) 3.00; 95% confidence interval (CI) 2.27-3.96]. This increased sustained virological response with peginterferon and ribavirin was found for patients with HCV genotype 1 or 4 (OR 4.40; 95% CI 2.75-7.03) and genotype 2 or 3 (OR 2.56; 95% CI 1.71-3.85). Sustained virological responses were also higher with peginterferon and ribavirin as compared with peginterferon monotherapy (OR 2.60; 95% CI 1.84-3.67). Severe adverse effects (OR 1.09; 95% CI 0.74-1.4) and withdrawal rates (OR 0.97; 95% CI 0.75-1.25) were similar between patients treated with peginterferon plus ribavirin and patients treated with interferon plus ribavirin. Conclusions Patients with chronic HCV/HIV coinfection have a greater likelihood of achieving a sustained virological response with peginterferon plus ribavirin. The likelihoods of serious adverse effects and study withdrawal were similar. C1 VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. RP Saab, S (reprint author), Pfleger Liver Inst, 200 UCLA Med Plaza,Suite 214,Box 957302, Los Angeles, CA 90095 USA. EM Ssaab@mednet.ucla.edu NR 45 TC 15 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD JUL PY 2007 VL 8 IS 5 BP 312 EP 321 DI 10.1111/j.1468-1293.2007.00476.x PG 10 WC Infectious Diseases SC Infectious Diseases GA 177CB UT WOS:000247130100008 PM 17561878 ER PT J AU Braun, SE Lu, XBV Wong, FE Connole, M Qiu, G Chen, ZP Slepushkina, T Slepushkin, V Humeau, LM Dropulic, B Johnson, RP AF Braun, Stephen E. Lu, Xiaobin V. Wong, Fay Eng Connole, Michelle Qiu, Gang Chen, Ziping Slepushkina, Tatiana Slepushkin, Vladimir Humeau, Laurent M. Dropulic, Boro Johnson, R. Paul TI Potent inhibition of simian immunodeficiency virus (SIV) replication by an SIV-based lentiviral vector expressing antisense env SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; RHESUS-MONKEYS; GENE-TRANSFER; STABLE TRANSDUCTION; HIV-1 REPLICATION; PROGENITOR CELLS; CD34(+) CELLS; NONDIVIDING CELLS; NONHUMAN-PRIMATES; AIDS VACCINE AB In light of findings demonstrating that the macaque TRIM5 alpha protein inhibits infection of cells by human immunodeficiency virus (HIV)-1, simian immunodeficiency virus (SIV)-based lentiviral vectors may have distinct advantages over HIV-1 vectors for the transduction of macaque hematopoietic stem cells. We evaluated the ability of an SIV vector (VRX859) encoding an antisense SIV envelope sequence and enhanced green fluorescent protein (GFP) to inhibit viral replication and to transduce rhesus CD34(+) lymphoid progenitor cells. After infection with homologous SIV strains, CD4(+) cell lines transduced with VRX859 exhibited more than 600-fold inhibition of viral replication compared with control cells. Less inhibition was observed with the divergent SIV strain SIVsmE660. Partial inhibition of a chimeric simian-human immunodeficiency virus, which contains an HIV-1 envelope in an SIV backbone, was observed, suggesting that the SIV vector also contributes to viral inhibition independent of the antisense envelope inhibitor. Transduction of rhesus CD34(+) cells, with VRX859 at various multiplicities of infection resulted in transduction efficiencies comparable to those obtained with the HIV vector VRX494. However, when we evaluated transduction of rhesus T lymphocyte progenitors by examining GFP expression in CD4+ T cells derived from transduced CD34+ cells, we observed more efficient transduction with the SIV-based vector. GFP(+)CD4(+) T cells derived from VRX859-transduced CD34+ cells strongly inhibited SIVmac239 replication as compared with control CD4+ T cells. The ability of this SIV-based vector to mediate potent inhibition of SIV replication, coupled with its efficient transduction of rhesus hernatopoietic progenitor cells, make it an important candidate for proof-of-principle experiments of stem cell gene therapy in the SIV-macaque model. C1 Harvard Univ, Sch Med, Dept Immunol, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. VIRxSYS, Gaithersburg, MD 20877 USA. Johns Hopkins Univ, Sch Med, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Massachusetts Gen Hosp, Partners AIDS Res Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. RP Braun, SE (reprint author), Harvard Univ, Sch Med, Dept Immunol, New England Reg Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM stephen_braun@hms.harvard.edu FU NCI NIH HHS [CA 73473]; NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI 42851] NR 49 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2007 VL 18 IS 7 BP 653 EP 664 DI 10.1089/hum.2007.003 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 196AR UT WOS:000248454300007 PM 17600461 ER PT J AU Adler, GK Williams, GH AF Adler, Gail K. Williams, Gordon H. TI Aldosterone - Villain or protector? SO HYPERTENSION LA English DT Editorial Material ID DYSFUNCTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Endocrinol Diabet & Hypertnes,Cardiovasc Endo, Boston, MA 02115 USA. RP Williams, GH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Endocrinol Diabet & Hypertnes,Cardiovasc Endo, Boston, MA 02115 USA. EM gwilliams@partners.org FU NHLBI NIH HHS [HL069208] NR 9 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2007 VL 50 IS 1 BP 31 EP 32 DI 10.1161/HYPERTENSIONAHA.107.090894 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600005 PM 17533198 ER PT J AU Rana, S Karumanchi, SA Levine, RJ Venkatesha, S Rauh-Hain, JA Tamez, H Thadhani, R AF Rana, Sarosh Karumanchi, S. Ananth Levine, Richard J. Venkatesha, Shivalingappa Rauh-Hain, Jose Alejandro Tamez, Hector Thadhani, Ravi TI Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia SO HYPERTENSION LA English DT Article DE antiangiogenic factors; sFlt1; soluble endoglin; preeclampsia; predictive test ID GROWTH-FACTOR RECEPTOR-1; ANGIOGENIC FACTORS; SOLUBLE ENDOGLIN; HYPOXIA AB Concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) increase in maternal blood with the approach of clinical preeclampsia. Although alterations in these circulating antiangiogenic factors herald the signs and symptoms of preeclampsia, in vitro studies suggest they may also play a role in regulating early placental cytotrophoblast functions. Early pregnancy changes in sFlt1 and sEng may thus identify women destined to develop preeclampsia. We performed a nested case-control study of 39 women who developed preeclampsia and 147 contemporaneous normotensive controls each with serum collected in the first (11 to 13 weeks of gestation) and second (17 to 20 weeks) trimesters. Whereas levels of sFlt1 and sEng at 11 to 13 weeks were similar between cases and controls (sFlt1: 3.5 +/- 0.3 ng/mL versus 3.0 +/- 0.1, P = 0.14; sEng 6.9 +/- 0.3 ng/mL versus 6.6 +/- 0.2, P = 0.37, respectively), at 17 to 20 weeks both were elevated in the women destined to develop preeclampsia (sFlt1: 4.1 +/- 0.5 ng/mL versus 3.1 +/- 0.1, P < 0.05; sEng, 6.4 +/- 0.4 ng/mL versus 5.2 +/- 0.1, P < 0.01). Women who developed preterm (< 37 weeks) preeclampsia demonstrated even greater sequential changes: difference [ delta{d}] between second and first trimester levels: dsFlt1, 0.63 +/- 0.91 ng/mL in preterm PE versus 0.05 +/- 0.15 in controls; dsEng, 0.73 +/- 0.77 ng/mL versus -1.32 +/- 0.18, P < 0.01. Similar findings were noted in a cross-sectional analysis of specimens collected from the Calcium for Preeclampsia Prevention Study. In conclusion, sequential changes in antiangiogenic factors during early pregnancy may be useful for predicting preterm preeclampsia. C1 Brown Univ, Women & Infants Hosp, Div Maternal Fetal Med, Providence, RI 02912 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA 02115 USA. NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU Intramural NIH HHS; NHLBI NIH HHS [HL079594]; NICHD NIH HHS [HD 39223]; NIDDK NIH HHS [DK 065997, DK 67397] NR 21 TC 152 Z9 161 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2007 VL 50 IS 1 BP 137 EP 142 DI 10.1161/HYPERTENSIONAHA.107.087700 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600024 PM 17515455 ER PT J AU Hyde, D Miller, E Brooks, DH Ntziachristos, V AF Hyde, Damon Miller, Eric Brooks, Dana H. Ntziachristos, Vasilis TI A statistical approach to inverting the Born ratio SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE fluorescence; inverse problems; optical imaging ID FLUORESCENCE TOMOGRAPHY; DIFFUSION TOMOGRAPHY; MEDIA; RECONSTRUCTION; LIGHT AB We examine the problem of fluorescence molecular tomography using the normalized Born approximation, termed herein the Born ratio, from a statistical perspective. Experimentally verified noise models for received signals at the excitation and emission wavelengths are combined to generate a stochastic model for the Born ratio. This model is then utilized within a maximum likelihood framework to obtain an inverse solution based on a fixed point iteration. Results are presented for three experimental scenarios: phantom data with a homogeneous background, phantoms implanted within a small animal, and in vivo data using an exogenous probe. C1 Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Hyde, D (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. EM dhyde@ece.neu.edu; elmiller@ece.neu.edu; brooks@ece.neu.edu; vasilis@helix.mgh.harvard.edu RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 NR 23 TC 17 Z9 18 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2007 VL 26 IS 7 BP 893 EP 905 DI 10.1109/TMI.2007.895467 PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 187FJ UT WOS:000247832700001 PM 17649903 ER PT J AU Pao, LI Lam, KP Henderson, JM Kutok, JL Alimzhanov, M Nitschke, L Thomas, ML Neel, BG Rajewsky, K AF Pao, Lily I. Lam, Kong-Peng Henderson, Joel M. Kutok, Jeffery L. Alimzhanov, Marat Nitschke, Lars Thomas, Matthew L. Neel, Benjamin G. Rajewsky, Klaus TI B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity SO IMMUNITY LA English DT Article ID VIABLE MOTH-EATEN; BONE-MARROW CELLS; MICE REVEAL; RECEPTOR; GENE; CD22; RESPONSES; IDENTIFICATION; LYMPHOCYTES; THRESHOLDS AB Spontaneous loss-of-function mutations in the protein-tyrosine phosphatase Shp1 cause the motheaten phenotype, characterized by widespread inflammation and autoimmunity. Because Shp1 is expressed in all hematopoietic cells, it has been unclear which aspects of the motheaten phenotypes are primary effects of Shp1 deficiency. We generated mice (Ptpn6(f/f), CD19-cre) that delete Shpl specifically in B cells. Analysis of these mice indicates that the increase in B-1a cells in motheaten mice is a cell-autonomous consequence of Shpl deficiency. Shp1-deficient B-1a cells could be derived from adult bone marrow and had N-nucleotide additions, consistent with an adult origin. Shpl1 deficiency altered calcium response evoked by B cell antigen receptors and impaired CD40-evoked proliferation. Young Ptpn6(f/f),-CD19-cre mice exhibited elevated serum immunoglobulins and impaired antibody responses to immunization, whereas older Ptpn6(f/f)-CD19-cre mice developed systemic autoimmunity, characterized by DNA antibodies and immune complex glomerulonephritis. Thus, Shpl deficiency in B cells alone perturbs B cell development and causes autoimmune disease. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02115 USA. Agcy Sci Technol & Res, Inst Biomed Sci, Lab Mol & Cellular Immunol, Singapore 138673, Singapore. Singapore Immunol Network, Singapore 138673, Singapore. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Genet, D-91058 Erlangen, Germany. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. RP Pao, LI (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02115 USA. EM lpao@bidmc.harvard.edu; rajewsky@cbr.med.harvard.edu RI Lam, Kong-Peng/G-5374-2012; OI Lam, Kong-Peng/0000-0002-1316-4333 FU NIAID NIH HHS [AI054636]; NIDDK NIH HHS [R01-DK50693, P01-DK50654] NR 42 TC 112 Z9 112 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2007 VL 27 IS 1 BP 35 EP 48 DI 10.1016/j.immuni.2007.04.016 PG 14 WC Immunology SC Immunology GA 195FO UT WOS:000248398100007 PM 17600736 ER PT J AU Butte, MJ Keir, ME Phamduy, TB Sharpe, AH Freeman, GJ AF Butte, Manish J. Keir, Mary E. Phamduy, Theresa B. Sharpe, Arlene H. Freeman, Gordon J. TI Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses SO IMMUNITY LA English DT Article ID DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; IMMUNE-RESPONSES; PD-1 EXPRESSION; IN-VIVO; FAMILY; CTLA-4; ACTIVATION; LIGATION; ANTIGEN AB Pathways in the B7:CD28 family of costimulatory molecules regulate T cell activation and tolerance. B7-dependent responses in Cd28(-/-) Ctla4(-/-) T cells together with reports of stimulatory and inhibitory functions for Programmed Death-1 Ligand 1 or 2 molecules (PD-L1 or PD-L2) have suggested additional receptors for these 137 family members. We show that B7-1 and PD-L1 interacted with affinity intermediate to that of B7-1:CD28 and B7-1:CTLA-4. The PD-L1:B7-1 interface overlapped with the B7-1:CTLA-4 and PD-L1:PD-1 (Programmed Death-1) interfaces. T cell activation and cytokine production were inhibited by the interaction of B7-1 with PD-L1. The responses of PD-1 -deficient versus PD-1,B7-1 double-deficient T cells to PD-L1 and of CD28,CTLA-4 double-deficient versus CD28,CTLA-4,PD-L1 triple-deficient T cells to B7-1 demonstrated that PD-L1 and B7-1 interact specifically to inhibit T cell activation. Our findings point to a substantial bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arlene_sharpe@hms.harvard.edu OI Butte, Manish/0000-0002-4490-5595 FU NCRR NIH HHS [S10 RR017948, S10RR017948-01A1]; NIAID NIH HHS [R01 AI040614-05, P01 AI056299, P01 AI056299-04, P01 AI056299-05, P01 AI56299, R01 AI038310, R01 AI038310-05, R01 AI038310-06, R01 AI038310-07, R01 AI040614, R01 AI040614-06, R01 AI040614-07, R01 AI38310, R01 AI46414, R37 AI038310] NR 53 TC 540 Z9 564 U1 5 U2 39 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2007 VL 27 IS 1 BP 111 EP 122 DI 10.1016/j.immuni.2007.05.016 PG 12 WC Immunology SC Immunology GA 195FO UT WOS:000248398100013 PM 17629517 ER PT J AU Fan, W Idnurm, A Breger, J Mylonakis, E Heitman, J AF Fan, Weihua Idnurm, Alexander Breger, Julia Mylonakis, Eleftherios Heitman, Joseph TI Eca1, a Sarcoplasmic/Endoplasmic reticulum Ca(2+)-ATPase, is involved in stress tolerance and virulence in Cryptococcus neoformans SO INFECTION AND IMMUNITY LA English DT Article ID HIGH-TEMPERATURE GROWTH; PROTEIN-KINASE HOMOLOG; CANDIDA-ALBICANS; LEGIONELLA-PNEUMOPHILA; CAENORHABDITIS-ELEGANS; SACCHAROMYCES-CEREVISIAE; FUNGICIDE RESISTANCE; SUPEROXIDE-DISMUTASE; HYPHAL ELONGATION; FUNGAL VIRULENCE AB The basidiomycetous fungal pathogen Cryptococcus neoformans is adapted to survive challenges in the soil and environment and within the unique setting of the mammalian host. A C neoformans mutant was isolated with enhanced virulence in a soil amoeba model that nevertheless exhibits dramatically reduced growth at mammalian body temperature (37 degrees C). This mutant phenotype results from an insertion in the ECAI gene, which encodes a sarcoplasmic/endoplasmic reticulum (ER) Ca(2+) -ATPase (SERCA)-type calcium pump. Infection in murine macrophages, amoebae (Acanthamoeba castellanii), nematodes (Caenorhabditis elegans), and wax moth (Galleria mellonella) larvae revealed that the eca1 mutants are virulent or hypervirulent at permissive growth temperatures but attenuated at 37 degrees C. Deletion mutants lacking the entire ECA1 gene were also hypersensitive to the calcineurin inhibitors cyclosporin and FK506 and to ER and osmotic stresses. An eca1 Delta cna1 Delta mutant lacking both Eca1 and the calcineurin catalytic subunit was more sensitive to high temperature and ER stresses than the single mutants and exhibited reduced survival in C. elegans and attenuated virulence towards wax moth larvae at temperatures that permit normal growth in vitro. Eca1 is likely involved in maintaining ER function, thus contributing to stress tolerance and virulence acting in parallel with Ca(2+) calcineurin signaling. C1 Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. BASF Plant Sci, Res Triangle Pk, NC 27709 USA. RP Heitman, J (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Room 322 CARL Bldg,Box 3546, Durham, NC 27710 USA. EM heitm001@duke.edu RI Idnurm, Alexander/K-8558-2013 OI Idnurm, Alexander/0000-0001-5995-7040 FU NIAID NIH HHS [AI 063443, K08 AI 63084, AI 042159, K08 AI063084, R01 AI042159, R01 AI063443, T32 AI 52080, T32 AI052080] NR 76 TC 35 Z9 37 U1 1 U2 8 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 JUL PY 2007 VL 75 IS 7 BP 3394 EP 3405 DI 10.1128/IAI.01977-06 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185JP UT WOS:000247707600019 PM 17502401 ER PT J AU Diakonova, M Heifer, E Seveau, S Swanson, JA Kocks, C Rui, L Carlier, MF Carter-Su, C AF Diakonova, Maria Heifer, Emmanuele Seveau, Stephanie Swanson, Joel A. Kocks, Christine Rui, Liangyou Carlier, Marie-France Carter-Su, Christin TI Adapter protein SH2-B beta stimulates actin-based motility of Listera monocytogenes in a vasodilator-stimulated phosphoprotein (VASP)-dependent fashion SO INFECTION AND IMMUNITY LA English DT Article ID ENA/VASP PROTEINS; ARP2/3 COMPLEX; GROWTH-FACTOR; INTRACELLULAR MOTILITY; FIBROBLAST MOTILITY; BINDING PROTEIN; F-ACTIN; IDENTIFICATION; VASP; NUCLEATION AB SH2-B beta (Src homology 2 B beta) is an adapter protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-B beta is also required for maximal actin-based motility of Listeria monocytogenes. SH2-B beta localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B-/- mice. Both recruitment of SH2-B beta to Listeria and SH2-B beta stimulation of actin-based propulsion require the vasodilator-stimulated phosphoprotein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-B beta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-B beta binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-B beta and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads . C1 Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA. Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI USA. CNRS, Dynamique Cytosquelette Lab Enzymol Biochim S, Gif Sur Yvette, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Diakonova, M (reprint author), Univ Toledo, Dept Biol Sci, 2801 W Bancroft St, Toledo, OH 43606 USA. EM mdiakon@utnet.utoledo.edu RI Seveau, Stephanie/E-4060-2011; Swanson, Joel/P-4362-2014; OI Swanson, Joel/0000-0003-0900-8212; Diakonova, Maria/0000-0002-4554-2730 FU NIAID NIH HHS [R01 AI 35950, R01 AI035950, R01 AI035950-14, R21 AI 057778, R21 AI057778]; NIDDK NIH HHS [R01 DK 065122, 5P60 DK 20572, P60 DK 20572, P60 DK020572, R01 DK 54222, R01 DK054222, R01 DK065122] NR 52 TC 5 Z9 5 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2007 VL 75 IS 7 BP 3581 EP 3593 DI 10.1128/IAI.00214-07 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185JP UT WOS:000247707600040 PM 17452473 ER PT J AU Stout, JE Muder, RR Mietzner, S Wagener, MM Perri, MB DeRoos, K Goodrich, D Arnold, W Williamson, T Ruark, O Treadway, C Eckstein, EC Marshall, D Rafferty, ME Sarro, K Page, J Jenkins, R Oda, G Shimoda, KJ Zervos, MJ Bittner, M Camhi, SL Panwalker, AP Donskey, CJ Nguyen, MH Holodniy, M Yu, VL AF Stout, Janet E. Muder, Robert R. Mietzner, Sue Wagener, Marilyn M. Perri, Mary Beth DeRoos, Kathleen Goodrich, Dona Arnold, William Williamson, Theresa Ruark, Ola Treadway, Christine Eckstein, Elizabeth C. Marshall, Debra Rafferty, Mary Ellen Sarro, Kathleen Page, Joann Jenkins, Robert Oda, Gina Shimoda, Kathleen J. Zervos, Marcus J. Bittner, Marvin Camhi, Sharon L. Panwalker, Anand P. Donskey, Curtis J. Nguyen, Minh-Hong Holodniy, Mark Yu, Victor L. CA Legionella Study Grp TI Role of environmental surveillance in determining the risk of hospital-acquired legionellosis: A national surveillance study with clinical correlations SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID NOSOCOMIAL LEGIONNAIRES-DISEASE; PNEUMOPHILA; WATER; PREVENTION; SEROGROUP-1; PNEUMONIA; MONOCHLORAMINE; DIAGNOSIS; PATTERNS; CULTURES AB Objective. Hospital-acquired Legionella pneumonia has a fatality rate of 28%, and the source is the water distribution system. Two prevention strategies have been advocated. One approach to prevention is clinical surveillance for disease without routine environmental monitoring. Another approach recommends environmental monitoring even in the absence of known cases of Legionella pneumonia. We determined the Legionella colonization status of water systems in hospitals to establish whether the results of environmental surveillance correlated with discovery of disease. None of these hospitals had previously experienced endemic hospital-acquired Legionella pneumonia. Design. Cohort study. kll;llSetting. Twenty US hospitals in 13 states. Interventions. Hospitals performed clinical and environmental surveillance for Legionella from 2000 through 2002. All specimens were shipped to the Special Pathogens Laboratory at the Veterans Affairs Pittsburgh Medical Center. Results. Legionella pneumophila and Legionella anisa were isolated from 14 (70%) of 20 hospital water systems. Of 676 environmental samples, 198 (29%) were positive for Legionella species. High-level colonization of the water system (30% or more of the distal outlets were positive for L. pneumophila) was demonstrated for 6 (43%) of the 14 hospitals with positive findings. L. pneumophila serogroup 1 was detected in 5 of these 6 hospitals, whereas 1 hospital was colonized with L. pneumophila serogroup 5. A total of 633 patients were evaluated for Legionella pneumonia from 12 (60%) of the 20 hospitals: 377 by urinary antigen testing and 577 by sputum culture. Hospital-acquired Legionella pneumonia was identified in 4 hospitals, all of which were hospitals with L. pneumophila serogroup 1 found in 30% or more of the distal outlets. No cases of disease due to other serogroups or species (L. anisa) were identified. Conclusion. Environmental monitoring followed by clinical surveillance was successful in uncovering previously unrecognized cases of hospital-acquired Legionella pneumonia. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Vet Affairs Med Ctr, Butler, PA USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Vet Affairs Med Ctr, Omaha, NE USA. So Arizona Healthcare Syst, Tucson, AZ USA. Vet Affairs Med Ctr, Wilmington, DE USA. Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA. Vet Affairs Med Ctr, Dayton, OH USA. Stratton Vet Affairs Med Ctr, Albany, NY USA. Vet Affairs Med Ctr, Iowa City, IA USA. Vet Affairs Med Ctr, Gainesville, FL 32608 USA. Vet Affairs Med Ctr, Palo Alto, CA USA. Vet Affairs Med Ctr, Long Beach, CA USA. RP Yu, VL (reprint author), Special Pahtogens Lab, 1401 Forbes Ave,Suite 209, Pittsburgh, PA 15219 USA. EM vly@pitt.edu NR 36 TC 65 Z9 69 U1 0 U2 8 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 JUL PY 2007 VL 28 IS 7 BP 818 EP 824 DI 10.1086/518754 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 205NR UT WOS:000249121400008 PM 17564984 ER PT J AU Papakostas, GI Kornstein, SG Clayton, AH Soares, CN Hallett, LA Krishen, A Tucker, VL AF Papakostas, George I. Kornstein, Susan G. Clayton, Anita H. Soares, Claudio N. Hallett, Lindsay A. Krishen, Alok Tucker, Vivian L. TI Relative antidepressant efficacy of bupropion and the selective serotonin reuptake inhibitors in major depressive disorder: gender-age interactions SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE age; bupropion; depression; gender; major depressive disorder; response; selective serotonin reuptake inhibitors ID SUSTAINED-RELEASE; DOUBLE-BLIND; SERTRALINE; FLUOXETINE; VENLAFAXINE; OUTPATIENTS; PAROXETINE; SSRIS; WOMEN; MOOD AB To determine whether age/gender-based differences in efficacy exist between bupropion and the selective serotonin reuptake inhibitors for major depressive disorder, we pooled the findings of 10 double-blind studies comparing bupropion with a selective serotonin reuptake inhibitor. Men (N=943) and women (N=1179) were divided into three age groups (younger than 40, 40-55, older than 55). Improvement in terms of the 17-item Hamilton Depression Rating Scale, as well as the Bech melancholia, anxiety-somatization, and insomnia factors of the Hamilton Depression Rating Scale was compared between the two treatment groups. Of 64 pair-wise comparisons, only one was statistically significant. Specifically, more women treated with a selective serotonin reuptake inhibitor experienced a 50% or greater decrease in Hamilton Depression Rating Scale Anxiety-Somatization scores (58.8 versus 63.8%, P=0.0394). No difference, however, was seen in the degree of resolution of Hamilton Depression Rating Scale Anxiety-Somatization scores (continuous measure) between women treated with bupropion versus a selective serotonin reuptake inhibitor (P= 0.114). Bupropion and the selective serotonin reuptake inhibitors, thus, appear to be equally effective in treating depressive symptoms, as well as anxious/somatic symptoms and insomnia in depression. No gender-related or age-related differences were found except that greater improvement was seen in anxious/somatic symptoms of depression among women during selective serotonin reuptake inhibitor treatment. This finding could, however, not be replicated when improvement in anxious/somatic symptoms was defined as a continuous measure. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. Univ Virginia, Dept Psychiat Med, Hlth Syst, Charlottesville, VA USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 30 TC 14 Z9 14 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JUL PY 2007 VL 22 IS 4 BP 226 EP 229 DI 10.1097/YIC.0b013e32819f8400 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 178NE UT WOS:000247226600007 PM 17519646 ER PT J AU Ray, KK Cannon, CP Braunwald, E AF Ray, K. K. Cannon, C. P. Braunwald, E. TI Recent trials of lipid lowering SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; ACUTE CORONARY SYNDROMES; PLACEBO-CONTROLLED TRIAL; HIGH-DOSE ATORVASTATIN; INTENSIVE STATIN THERAPY; MRC/BHF HEART PROTECTION; LOW-DENSITY-LIPOPROTEIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION AB The global burden of coronary artery disease has pushed lipid-lowering therapy to the forefront of medical management of this condition. Recent clinical trials have compared the efficacy of more intensive lipid lowering with statins against the normal standard of care. Other agents such as fibrates, glitazones, which also favourably modify lipid levels have also been assessed recently. This narrative review summarises the key recent clinical trials of lipid lowering since 2004 and their implications for future patient care. C1 Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ray, KK (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Worts Causeway, Cambridge CB1 8RN, England. EM koshray@gmail.com NR 43 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD JUL PY 2007 VL 61 IS 7 BP 1145 EP 1159 DI 10.1111/j.1742-1241.2007.01425.x PG 15 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 179VZ UT WOS:000247319600017 PM 17577297 ER PT J AU Takahashi, T Morris, EA Trippel, SB AF Takahashi, Toshiaki Morris, Elisabeth A. Trippel, Stephen B. TI Bone morphogenetic protein-2 and-9 regulate the interaction of insulin-like growth factor-I with growth plate chondrocytes SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE bone morphogenetic proteins; insulin-like growth factor-I; growth plate chondrocytes ID FACTOR BINDING-PROTEINS; DIFFERENTIATED PHENOTYPE; OSTEOGENIC PROTEIN-1; DNA-SYNTHESIS; CELLS; PROLIFERATION; EXPRESSION; RECEPTORS; BMP-2; MAINTENANCE AB Insulin-like growth factor-I (IGF-I) is thought to play an important role in skeletal growth and development through its mitogenic and anabolic effects on epiphyseal growth plate chondrocytes. The bone morphogenetic proteins (BMPs) have been shown to promote endochondral osteogenesis, and some members of the BMP family, including BMP-2 and BMP-9, have anabolic effects on chondrocyte metabolism. We tested the hypothesis that BMP-2 and BMP-9 interact with IGF-I to modulate growth plate chondrocyte mitotic activity. IGF-I, but neither BMP-2 nor BMP-9, stimulated chondrocyte DNA synthesis. However, both BMP-2 and BMP-9 augmented the mitogenic action of IGF-I. BMP-2, but not BMP-9 increased IGF-I binding to growth plate chondrocytes in kinetic studies. In affinity labeling studies, I-125-IGF-I predominantly labeled an Mr similar to 135-kDa moiety, consistent with the a subunit of the type 1 IGF receptor and an Mr similar to 250-kDa moiety consistent with the type 2 IGF receptor. I-125-IGF-I labeling also appeared at Mr similar to 43-kDa, consistent with I-125-IGF-I binding to insulin-like growth binding protein-3. Treatment of chondrocytes with BMP-2, but not with BMP-9, increased the intensity of the Mr similar to 135-kDa band and decreased the intensity of the Mr similar to 43-kDa band. Taken together, these data suggest that the BMPs may modulate the action of IGF-I via the type 1 IGF receptor and/or IGF binding proteins. C1 Ehime Univ, Grad Sch Med, Dept Bone & Joint Surg, Toon, Ehime 7910295, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Wyeth Res, Dept Womens Hlth & Musculoskeletal Biol, Cambridge, MA 02140 USA. Indiana Univ, Sch Med, Dept Orthopaed Surg, Indianapolis, IN 46202 USA. RP Takahashi, T (reprint author), Ehime Univ, Grad Sch Med, Dept Bone & Joint Surg, Toon, Ehime 7910295, Japan. EM takahast@m.ehime-u.ac.jp FU NIAMS NIH HHS [AR31068] NR 31 TC 4 Z9 6 U1 0 U2 0 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 JUL PY 2007 VL 20 IS 1 BP 53 EP 57 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 182GK UT WOS:000247492900007 PM 17549388 ER PT J AU Krejcarek, SC Grant, PE Henson, JW Tarbell, NJ Yock, TI AF Krejcarek, Stephanie C. Grant, P. Ellen Henson, John W. Tarbell, Nancy J. Yock, Torunn I. TI Physiologic and radiographic evidence of the distal edge of the proton beam in craniospinal irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE proton radiotherapy; craniospinal irradiation; late effects; medulloblastoma; dosimetry ID PEDIATRIC BRAIN-TUMORS; RADIATION-THERAPY; MEDULLOBLASTOMA; MARROW AB Purpose: Fatty replacement of bone marrow resulting from radiation therapy can be seen on T1-weighted magnetic resonance (MR) images. We evaluated the radiographic appearance of the vertebral bodies in children treated with proton craniospinal irradiation (CSI) to illustrate the distal edge effect of proton radiotherapy. Methods and Materials: The study cohort consisted of 13 adolescents aged 12-18 years who received CSI with proton radiotherapy at Massachusetts General Hospital. Ten of these patients had reached maximal or near-maximal growth. Proton beam radiation for these 10 patients was delivered to the thecal sac and exiting nerve roots only, whereas the remaining 3 patients had a target volume that included the thecal sac, exiting nerve roots, and entire vertebral bodies. Median CSI dose was 27 [range, 23.4-36] cobalt gray equivalent (CGE) given in 1.8-CGE fractions. Magnetic resonance images of the spine were obtained after completion of radiotherapy. Results: Magnetic resonance images of patients who received proton radiotherapy to the thecal sac only demonstrate a sharp demarcation of hyperintense T1-weighted signal in the posterior aspects of the vertebral bodies, consistent with radiation-associated fatty marrow replacement. Magnetic resonance images of the patients prescribed proton radiotherapy to the entire vertebral column had corresponding hyperintense T1-weighted signal involving the entire vertebral bodies. Conclusion: The sharp delineation of radiation-associated fatty marrow replacement in the vertebral bodies demonstrates the rapid decrease in energy at the edge of the proton beam. This provides evidence for a sharp fall-off in radiation dose and supports the premise that proton radiotherapy spares normal tissues unnecessary irradiation. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 331 100 Blossom St, Boston, MA 02114 USA. EM tyock@partners.org FU NCI NIH HHS [P01 CA021239, P01 CA021239-27] NR 12 TC 25 Z9 25 U1 0 U2 2 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 JUL 1 PY 2007 VL 68 IS 3 BP 646 EP 649 DI 10.1016/j.ijrobp.2007.02.021 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 179JB UT WOS:000247284600001 PM 17449195 ER PT J AU Parodi, K Paganetti, H Shih, HA Michaud, S Loeffler, JS DeLaney, TF Liebsch, NJ Munzenrider, JE Fischman, AJ Knopf, A Bortfeld, T AF Parodi, Katia Paganetti, Harald Shih, Helen A. Michaud, Susan Loeffler, Jay S. DeLaney, Thomas F. Liebsch, Norbert J. Munzenrider, John E. Fischman, Alan J. Knopf, Antje Bortfeld, Thomas TI Patient study of in vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE proton therapy; PET/CT; Monte Carlo ID MONTE-CARLO SIMULATIONS; PET; DISTRIBUTIONS; WASHOUT; RABBIT AB Purpose: To investigate the feasibility and value of positron emission tomography and computed tomography (PET/CT) for treatment verification after proton radiotherapy. Methods and Materials: This study included 9 patients with tumors in the cranial base, spine, orbit, and eye. Total doses of 1.8-3 GyE and 10 GyE (for an ocular melanoma) per fraction were delivered in I or 2 fields. Imaging was performed with a commercial PET/CT scanner for 30 min, starting within 20 min after treatment. The same treatment immobilization device was used during imaging for all but 2 patients. Measured PET/CT images were coregistered to the planning CT and compared with the corresponding PET expectation, obtained from CT-based Monte Carlo calculations complemented by functional information. For the ocular case, treatment position was approximately replicated, and spatial correlation was deduced from reference clips visible in both the planning radiographs and imaging CT. Here, the expected PET image was obtained from an analytical model. Results: Good spatial correlation and quantitative agreement within 30% were found between the measured and expected activity. For head-and-neck patients, the beam range could be verified with an accuracy of 1-2 turn in well-coregistered bony structures. Low spine and eye sites indicated the need for better fixation and coregistration methods. An analysis of activity decay revealed as tissue-effective half-lives of 800-1,150 s. Conclusions: This study demonstrates the feasibility of postradiation PET/CT for in vivo treatment verification. It also indicates some technological and methodological improvements needed for optimal clinical application. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Parodi, K (reprint author), Heidelberg Ion Therapy Ctr, Neuenheimer Feld 450, D-69120 Heidelberg, Germany. EM Katia.Parodi@med.uni-heidelberg.de FU NCI NIH HHS [5 P01 CA21239-25, P01 CA021239, P01 CA021239-25, P01 CA021239-28] NR 17 TC 179 Z9 179 U1 0 U2 12 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 JUL 1 PY 2007 VL 68 IS 3 BP 920 EP 934 DI 10.1016/j.ijrobp.2007.01.063 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 179JB UT WOS:000247284600038 PM 17544003 ER PT J AU Jassal, DS Shapiro, MD Neilan, TG Chaithiraphan, V Ferencik, M Teague, SD Brady, TJ Isselbacher, EM Cury, RC AF Jassal, Davinder S. Shapiro, Michael D. Neilan, Tomas G. Chaithiraphan, Vithaya Ferencik, Maros Teague, Shawn D. Brady, Thomas J. Isselbacher, Eric M. Cury, Ricardo C. TI 64-slice multidetector computed tomography (MDCT) for detection of aortic regurgitation and quantification of severity SO INVESTIGATIVE RADIOLOGY LA English DT Article DE computed tomography; echocardiography; aortic regurgitation ID CORONARY-ANGIOGRAPHY; ORIFICE AREA; INITIAL-EXPERIENCE; ROW CT; ACCURACY; ULTRASOUND; ROTATION; STENOSIS AB Background: Recent advances in 64-slice multidetector computed tomography (MDCT) provide an opportunity to assess coronary artery disease, left ventricular function and, potentially, valvular heart disease. Objective: To determine the ability of 64-MDCT to both detect and to quantify the severity of aortic regurgitation (AR), as compared with transthoracic echocardiography (TTE). Methods: We evaluated a total of 64 patients (43 males, mean age 63 +/- 11 years), 30 with varying severities of AR as assessed by TTE and 34 matched controls. The severity of AR by TTE was determined using the vena contracta, the ratio of jet to left ventricular outflow tract (LVOT) height, and the ratio of the jet to LVOT cross-sectional area. AR by MDCT was defined as a lack of coaptation of the aortic valve leaflets in diastole and, if detected, the maximum anatomic aortic regurgitant orifice was determined. Results: All 34 control patients without AR were correctly identified by MDCT. There were 14 patients with mild AR, 10 with moderate AR, and 6 with severe AR by TTE. Of these patients, MDCT correctly identified 21 patients with AR (sensitivity 70%, specificity 100%, positive predictive value [PPV] 100%, and negative predictive value [NPV] 79%). Anatomic regurgitant orifice area measured by MDCT correlated well with the TTE-derived vena contracta (r = 0.79, P < 0.001), ratio of jet to LVOT height (r = 0.79,P < 0.001), and ratio of jet to LVOT cross-sectional area (r = 0.75, P < 0.001). Conclusions: Direct planimetric measurement of the aortic valve anatomic regurgitant orifice area on 64-MDCT provides an accurate, noninvasive technique for detecting and quantifying AR. C1 St Boniface Gen Hosp, Inst Cardiovasc Sci, Bergen Cardiac Care Ctr, Dept Cardiac Sci,Cardiol Div, Winnipeg, MB R2H 2A6, Canada. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46204 USA. RP Jassal, DS (reprint author), St Boniface Gen Hosp, Inst Cardiovasc Sci, Bergen Cardiac Care Ctr, Dept Cardiac Sci,Cardiol Div, 409 Tache Ave, Winnipeg, MB R2H 2A6, Canada. EM djassal@sbgh.mb.ca NR 28 TC 35 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUL PY 2007 VL 42 IS 7 BP 507 EP 512 DI 10.1097/RLI.0b013e3180375556 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 183FW UT WOS:000247559100004 PM 17568273 ER PT J AU Cheng, XH Irimia, D Dixon, M Ziperstein, JC Demirci, U Zamir, L Tompkins, RG Toner, M Rodriguez, WR AF Cheng, Xuanhong Irimia, Daniel Dixon, Meredith Ziperstein, Joshua C. Demirci, Utkan Zamir, Lee Tompkins, Rionald G. Toner, Mehmet Rodriguez, William R. TI A microchip approach for practical label-free CD4+ T-cell counting of HIV-infected subjects in resource-poor settings SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4; HIV; microchip; microfluidic; monitoring; resource-poor settings ID FLOW; FACSCOUNT; FREQUENCY; AFRICA; SYSTEM; CHIP AB Simple affordable CD4 cell counting is urgently needed to stage and monitor HIV-infected patients in resource-limited settings. To address the limitations of current approaches, we designed a simple, label-free, and cost-effective CD4 cell counting device using microfluidic technology. We previously described the fabrication of a microfluidic system for high-efficiency isolation of pure Populations of CD4(+) T cells based on cell affinity chromatography operated under controlled flow. Here, we compare the performance of a rnicrofluidic CD4 cell counting device against standard flow cytometry in 49 HIV-positive subjects over a wide range of absolute CD4 Cell Counts. We observed a close correlation between CD4 cell counts from the microchip device and measurements by flow Cytometry, using unprocessed whole blood from HIV-positive adult Subjects. Sensitivities for distinguishing clinically relevant thresholds of 200, 350, and 500 cells/mu L are 0.86, 0.90, and 0.97, respectively. Specificity is 0.94 or higher at all thresholds. This device can serve as a functional cartridge for fast, accurate, affordable, and simple CD4 cell Counting in resource-limited settings. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Surg Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Rodriguez, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Surg Serv, 149 13th St, Boston, MA 02115 USA. EM wrodriguez@partners.org OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB002503] NR 26 TC 59 Z9 59 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2007 VL 45 IS 3 BP 257 EP 261 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 183KY UT WOS:000247572900001 PM 17414933 ER PT J AU Olson, CK Kutner, LA Warner, DE Almerigi, JB Baer, L Nicholi, AM Beresin, EV AF Olson, Cheryl K. Kutner, Lawrence A. Warner, Dorothy E. Almerigi, Jason B. Baer, Lee Nicholi, Armand M., II Beresin, Eugene V. TI Factors correlated with violent video game use by adolescent boys and girls SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescent; video games; media violence; survey ID MEDIA USE; HOSTILITY AB Purpose: To compare the video and computer game play patterns of young adolescent boys and girls, including factors correlated with playing violent games. Methods: Data collected in November/December, 2004 from children in grades 7 and 8 at two demographically diverse schools in Pennsylvania and South Carolina, using a detailed written self-reported survey. Results: Of 1254 participants (53% female, 47% male), only 80 reported playing no electronic games in the previous 6 months. Of 1126 children who listed frequently played game titles, almost half (48.8%) played at least one violent (mature-rated) game regularly (67.9% of boys and 29.2% of girls). One third of boys and 10.7% of girls play games nearly every day; only I in 20 plays often or always with a parent. Playing M-rated games is positively correlated (p <.001) with being male, frequent game play, playing with strangers over the Internet, having a game system and computer in one's bedroom, and using games to manage anger. Conclusions: Most young adolescent boys and many girls routinely play M-rated games. Implications for identifying atypical and potentially hannful patterns of electronic game use are discussed, as well as the need for greater media literacy among parents. (c) 2007 Society for Adolescent Medicine. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mental Hlth & Media,Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Michigan State Univ, Univ Outreach & Engagement, E Lansing, MI 48824 USA. RP Olson, CK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mental Hlth & Media,Dept Psychiat, Wang 812,Parkman St, Boston, MA 02114 USA. EM ckolson@partners.org NR 17 TC 68 Z9 69 U1 4 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUL PY 2007 VL 41 IS 1 BP 77 EP 83 DI 10.1016/j.jadohealth.2007.01.001 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 184BN UT WOS:000247616200011 PM 17577537 ER PT J AU Suhonen, R Schmidt, LA Radwin, L AF Suhonen, Riitta Schmidt, Lee A. Radwin, Laurel TI Measuring individualized nursing care: assessment of reliability and validity of three scales SO JOURNAL OF ADVANCED NURSING LA English DT Article DE Individualized Care Scale; instrument validation; Oncology Patients' Perceptions of the Quality of Nursing Care Scale; reliability; Schmidt Perception of Nursing Care Survey; validity ID PATIENTS PERCEPTIONS; INTERVENTIONS; INSTRUMENT; NURSES; SATISFACTION; EQUIVALENCE; TRANSLATION; RELATIVES; QUALITY AB Aim. This paper is a report of a study to assess the reliability and convergent validity of three measures of nursing care individualization. Background. Individualized care is a key element of nursing care quality, yet little is known about the extent to which it is implemented, its effects, and the factors that help or hinder nurses in giving individualized care. Therefore reliable and valid instruments are needed to measure individualized nursing care. Method. A cross-sectional correlational survey design was used. The purposive sample consisted of 861 patients from six hospitals in Finland (response rate 82%). Data were collected in 2004. The Individualized Care Scale was administered simultaneously with translated versions of the Schmidt's Perceptions of Nursing Care Survey and the Oncology Patients' Perceptions of the Quality of Nursing Care Scale. Internal consistency reliability and convergent validity were assessed for each scale. Findings. Evidence for convergent validity was identified between the Individualized Care Scale (part A/B), the Individualization subscale (r = 0.64 with Part A, r = 0.66 with part B) and the Seeing the Individual Patient subscale (r = 0.68 with part A, r = 0.71 with part B). Cronbach alpha coefficient was 0.97 for the Individualized Care Scale, 0.82 for Seeing the Individual Patient and 0.87 for the Individualization subscale. Conclusion. Data provided preliminary evidence for the convergent validity of the individualized care scales, as well as acceptable internal consistency reliability for each scale. These scales represent useful measures for assessing patients' perceptions of the individualization of nursing care received. C1 Turku Univ, Dept Nursing Sci, FIN-20520 Turku, Finland. Loyola Univ, Ctr Med, Maywood, IL 60153 USA. Loyola Univ, Niehoff Sch Nursing, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Suhonen, R (reprint author), Turku Univ, Dept Nursing Sci, FIN-20520 Turku, Finland. EM suhonen.riitta@kolumbus.fi OI Suhonen, Riitta/0000-0002-4315-5550 NR 39 TC 19 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD JUL PY 2007 VL 59 IS 1 BP 77 EP 85 DI 10.1111/j.1365-2468.2007.04282.x PG 9 WC Nursing SC Nursing GA 177DB UT WOS:000247132700009 PM 17537199 ER PT J AU Camargo, CA Clark, S Kaplan, MS Lieberman, P Wood, RA AF Camargo, Carlos A., Jr. Clark, Sunday Kaplan, Michael S. Lieberman, Philip Wood, Robert A. TI Regional differences in EpiPen prescriptions in the United States: The potential role of vitamin D SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE anaphylaxis; epidemiology; EpiPen; vitamin D ID REGULATORY T-CELLS; SUN EXPOSURE; ANAPHYLAXIS; EPIDEMIOLOGY; POPULATION; ALLERGY; MELANOMA; CHILDREN; RISK; D-3 AB Background: The epidemiology of anaphylaxis is uncertain, especially its geographic distribution. Objective: To address this deficit, we examined regional rates of EpiPen prescriptions in the United States. Methods: EpiPen prescriptions in 2004 were obtained for all 50 states and Washington, DC, from NDCHealth, Pharmaceutical Audit Suite (Alpharetta, Ga). Data included the number of total filled prescriptions, including refills, and the actual number of EpiPens prescribed. Several data sets were used to obtain state-specific populations, as well as multiple demographic, health, and weather characteristics. State population was used to calculate the average number of prescriptions written per person. Results: Overall, there were 1,511,534 EpiPen prescriptions filled during 2004. These prescriptions accounted for 2,495,188 EpiPens. On average, there were 5.71 EpiPens prescribed per 1000 persons. Massachusetts had the highest number of prescriptions per 1000 persons (11.8), whereas Hawaii had the lowest (2.7). In addition to state-to-state variation, there was an obvious regional difference: New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine) had the highest values, with 8 to 12 EpiPen prescriptions per 1000 persons, whereas the southern states (between and including California and Mississippi) had only 3 prescriptions per 1000 persons. The New England finding persisted even when controlling for all available factors (eg, population demographic characteristics, number of health care providers, prescriptions for other medications). Conclusion: A strong north-south gradient was observed for the prescription of EpiPens in the United States, with the highest rates found in New England. Clinical implications: The regional differences in EpiPen prescribing may provide important etiologic clues (vitamin D status) and merit further investigation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Kaiser Permanente, Dept Allergy, Los Angeles, CA USA. Univ Tennessee, Coll Med, Memphis, TN 38163 USA. Johns Hopkins Med Ctr, Dept Pediat, Div Pediat Allergy & Immunol, Baltimore, MD USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr D Receptor Activat Res, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 29 TC 132 Z9 134 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2007 VL 120 IS 1 BP 131 EP 136 DI 10.1016/j.jaci.2007.03.049 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 190NS UT WOS:000248066400019 PM 17559916 ER PT J AU Celedon, JC Milton, DK Ramsey, CD Litonjua, AA Ryan, L Platts-Mills, TAE Gold, DR AF Celedon, Juan C. Milton, Donald K. Ramsey, Clare D. Litonjua, Augusto A. Ryan, Louise Platts-Mills, Thomas A. E. Gold, Diane R. TI Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE endotoxin; dust mite; wheeze; atopy; asthma ID DAY-CARE ATTENDANCE; HOUSE-DUST; 1ST YEAR; LIMULUS ASSAY; P-I; CHILDREN; WHEEZE; RISK; HISTORY; INFANCY AB Background: There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives: To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods: Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results: In multivariate analyses, early exposure to high levels of dust mite allergen (>= 10 mu g/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% Cl, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages I and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion: Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications: Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children. C1 Channing Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Hlth & Environm, Dept Work Environm, Lowell, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Virginia, Dept Med, Asthma & Allergy Ctr, Charlottesville, VA 22903 USA. RP Celedon, JC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM juan.celedon@channing.harvard.edu RI Ryan, Louise/A-4562-2009; Milton, Donald/G-3286-2010; Mac Sharry, John/B-5509-2011; OI Ryan, Louise/0000-0001-5957-2490; Milton, Donald/0000-0002-0550-7834; Mac Sharry, John/0000-0002-9528-6261; Litonjua, Augusto/0000-0003-0422-5875 FU NHLBI NIH HHS [R01 HL079966, HL04370, HL073373, HL079966, K01 HL004370, R01 HL073373]; NIAID NIH HHS [R01 AI035786, R01 AI035786-10]; NIEHS NIH HHS [ES07036, ES35786, R01 ES007036, R56 ES007036] NR 38 TC 122 Z9 128 U1 0 U2 3 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 JUL PY 2007 VL 120 IS 1 BP 144 EP 149 DI 10.1016/j.jaci.2007.03.037 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 190NS UT WOS:000248066400021 PM 17507083 ER PT J AU Dhond, RP Kettner, N Napadow, V AF Dhond, Rupali P. Kettner, Norman Napadow, Vitaly TI Neuroimaging acupuncture effects in the human brain SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID SOMATOSENSORY CORTICAL PLASTICITY; POSITRON-EMISSION-TOMOGRAPHY; CARPAL-TUNNEL-SYNDROME; PHANTOM-LIMB PAIN; SENSORY STIMULATION; SHAM ACUPUNCTURE; IMPLICATED ACUPOINTS; CONVERGENT NEURONS; SYMPATHETIC-NERVE; PLACEBO ANALGESIA AB Acupuncture is an ancient East Asian healing modality that has been in use for more than 2000 years. Unfortunately, its mechanisms of action are not well understood, and controversy regarding its clinical efficacy remains. Importantly, acupuncture needling often evokes complex somatosensory sensations and may modulate the cognitive/affective perception of pain, suggesting that many effects are supported by the brain and extending central nervous system (CNS) networks. Modern neuroimaging techniques such as functional magnetic resonance imaging, positron emission tomography, electroencephalography, and magnetoencephalography provide a means to safely monitor brain activity in humans and may be used to help map the neurophysiological correlates of acupuncture. In this review, we will summarize data from acupuncture neuroimaging research and discuss how these findings contribute to current hypotheses of acupuncture action. C1 Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Harvard Univ,Med Sch, Charlestown, MA 02129 USA. Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. RP Dhond, RP (reprint author), Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Harvard Univ,Med Sch, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM polly@nmr.mgh.harvard.edu FU NCCIH NIH HHS [K01-AT002166-01, P01-AT002048-02] NR 98 TC 97 Z9 107 U1 3 U2 19 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUL-AUG PY 2007 VL 13 IS 6 BP 603 EP 616 DI 10.1089/acm.2007.7040 PG 14 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 206YS UT WOS:000249219400004 PM 17718643 ER PT J AU Amory, JK Page, ST Anawalt, BD Coviello, AD Matsumoto, AM Bremner, WJ AF Amory, John K. Page, Stephanie T. Anawalt, Bradley D. Coviello, Andrea D. Matsumoto, Alvin M. Bremner, William J. TI Elevated end-of-treatment serum INSL3 is associated with failure to completely suppress spermatogenesis in men receiving male hormonal contraception SO JOURNAL OF ANDROLOGY LA English DT Article DE azoospermia; oligospermia ID INSULIN-LIKE FACTOR-3; ENANTHATE-INDUCED AZOOSPERMIA; RELAXIN-LIKE FACTOR; TESTOSTERONE ENANTHATE; LUTEINIZING-HORMONE; GONADOTROPIN-LEVELS; TESTIS; OLIGOZOOSPERMIA; LEVONORGESTREL; CRYPTORCHIDISM AB The administration of testosterone plus a progestogen functions as a male contraceptive by inhibiting the release of pituitary gonadotropins. After 3 to 4 months of treatment, most men are azoospermic or severely oligospermic (<= 1 million sperm/mL). However, 10% to 20% of men have persistent sperm production despite profound gonadotropin suppression. Since insulin-like factor 3 (INSL3) has been shown to prevent germ cell apoptosis in mice, we hypothesized that INSL3 might be higher in men with persistent spermatogenesis during treatment with male hormonal contraceptives. In a retrospective analysis, we measured serum INSL3 in 107 men from 3 recent male hormonal contraceptive studies and determined the relationship between suppression of spermatogenesis and serum INSL3. At the end of treatment 63 men (59%) were azoospermic and 44 men (41%) had detectable sperm in their ejaculates. Baseline INSL3 did not predict azoospermia; however, end of treatment serum INSL3 was significantly higher in non-azoospermic men compared with those with azoospermia (median [interquartile range]: 95 [73-127] pg/mL vs 80 [67-101] pg/mL; P =.03). Furthermore, serum INSL3 was positively correlated with sperm concentration (r =.25; P =.009) at the end of treatment and was significantly associated with nonazoospermia by multivariate logistic regression (P =.03). After 6 months of treatment with a hormonal male contraceptive regimen, higher serum INSL3 concentrations were associated with persistent sperm production. INSL3 may play a role in preventing complete suppression of spermatogenesis in some men on hormonal contraceptive regimens. This finding suggests that INSL3 may be a potential target for male contraceptive development. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Dept Med, Seattle, WA USA. Boston Univ, Dept Med, Boston, MA 02215 USA. Educ & Clin Ctr, Dept Geriatr Res, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Amory, JK (reprint author), Univ Washington, Box 356429,1959 NE Pacif, Seattle, WA 98195 USA. EM jamory@u.washington.edu FU NIA NIH HHS [K23 AG027238, K23 AG027238-03]; NICHD NIH HHS [K23 HD 45386, U54 HD 12629, U54 HD 42454] NR 28 TC 34 Z9 35 U1 0 U2 2 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JUL-AUG PY 2007 VL 28 IS 4 BP 548 EP 554 DI 10.2164/jandrol.106.002345 PG 7 WC Andrology SC Endocrinology & Metabolism GA 186FO UT WOS:000247764700014 PM 17314233 ER PT J AU Aslam, S Darouiche, RO AF Aslam, Saima Darouiche, Rabih O. TI Prolonged bacterial exposure to minocycline/rifampicin-impregnated vascular catheters does not affect antimicrobial activity of catheters SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 12-15, 2006 CL Toronto, CANADA SP Infect Dis Soc Amer DE minocycline/rifampicin-impregnated catheters; MIC; antimicrobial resistance ID CENTRAL VENOUS CATHETERS; IN-VITRO; RESISTANCE; EFFICACY; RISK; ANTIBIOTICS; ANTISEPTICS; RIFAMPIN AB Objectives: We assessed the in vitro effect of exposing various bacteria to minocycline/rifampicin-impregnated vascular catheters on the antimicrobial activity of the catheters and the antimicrobial susceptibility of tested organisms. Methods: Segments of minocycline/rifampicin-impregnated catheters were placed in agar plates inoculated with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus (VRE). Zones of inhibition were measured at 24 h, and colonies from the edge of this zone were retrieved after 72 h and inoculated onto new agar plates. A total of seven 72 h cycles were completed. We then measured the MICs of minocycline, rifampicin, vancomycin and linezolid for the collected strains. Results: The zones of inhibition of the four organisms remained stable after 21 days of sequential exposure to the impregnated catheters. The MICs of the antimicrobials remained constant, except for the MICs of rifampicin for MRSA and linezolid for MRSE, which increased slightly but remained within the susceptible range. Conclusions: Minocycline/rifampicin-impregnated catheters remain effective against MSSA, MRSA, MRSE and VRE, as evidenced by stable zones of inhibition following 21 day sequential exposure to these catheters. The increase in MIC of rifampicin for MRSA may be clinically relevant if the catheter remains in place for > 12 days though the strain remained susceptible to minocycline, there was no concurrent increase in the MIC of other tested drugs, and the zones of inhibition remained stable. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Ctr Prosthesis Infect, Houston, TX 77030 USA. RP Aslam, S (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Care Line,Room 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM saslam@bcm.tmc.edu NR 11 TC 5 Z9 5 U1 0 U2 0 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 JUL PY 2007 VL 60 IS 1 BP 148 EP 151 DI 10.1093/jac/dkm173 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 192DE UT WOS:000248180200022 PM 17525051 ER PT J AU Parthasarathy, S Jubran, A Laghi, F Tobin, MJ AF Parthasarathy, Sairam Jubran, Amal Laghi, Franco Tobin, Martin J. TI Sternomastoid, rib cage, and expiratory muscle activity during weaning failure SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sternomastoid muscles; respiratory muscles; mechanical ventilation ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; MECHANICALLY VENTILATED PATIENTS; PRESSURE SUPPORT VENTILATION; RESPIRATORY MUSCLES; DIAPHRAGMATIC FATIGUE; SCALENE; PATTERN; DYSPNEA; PATIENT AB We hypothesized that patients who fail weaning from mechanical ventilation recruit their inspiratory rib cage muscles sooner than they recruit their expiratory muscles, and that rib cage muscle recruitment is accompanied by recruitment of stemomastoid muscles. Accordingly, we measured stemomastoid electrical activity and changes in esophageal (Delta P-es) and gastric pressure (Delta P-ga) in 11 weaning-failure and 8 weaning-success patients. At the start of trial, failure patients exhibited a higher Delta p(ga)-to-Delta P-es ratio than did success patients (P = 0.05), whereas expiratory rise in P-ga was equivalent in the two groups. Between the start and end of the trial, failure patients developed additional increases in Delta P-ga-to-Delta P-es ratio (P < 0.0014) and the expiratory rise in P-ga also increased (P < 0.004). At the start of trial, stemomastoid activity was present in 8 of 11 failure patients contrasted with I of 8 success patients. Over the course of the trial, sternomastoid activity increased by 53.0 +/- 9.3% in the failure patients (P = 0.0005), whereas it did not change in the success patients. Failure patients recruited their respiratory muscles in a sequential manner. The sequence began with activity of diaphragm and greater-than-normal activity of inspiratory rib cage muscles; recruitment of sternomastoids and rib cage muscles approached near maximum within 4 min of trial commencement; expiratory muscles were recruited slowest of all. In conclusion, not only is activity of the inspiratory rib cage muscles increased during a failed weaning trial, but respiratory centers also recruit sternomastoid and expiratory muscles. Extradiaphragmatic muscle recruitment may be a mechanism for offsetting the effects of increased load on a weak diaphragm. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Hines, IL USA. RP Parthasarathy, S (reprint author), Univ Arizona, So Arizona VA Hlth Care Syst, Pulm & Crit Care Med Sect, 3601 S 6th Ave, Tucson, AZ 85723 USA. RI Parthasarathy, Sairam/L-1612-2013 NR 56 TC 32 Z9 35 U1 0 U2 0 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 JUL PY 2007 VL 103 IS 1 BP 140 EP 147 DI 10.1152/japplphysiol.00904.2006 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KK UT WOS:000248410900020 PM 17395760 ER PT J AU Felton, SM Gaige, TA Reese, TG Wedeen, VJ Gilbert, RJ AF Felton, Samuel M. Gaige, Terry A. Reese, Timothy G. Wedeen, Van J. Gilbert, Richard J. TI Mechanical basis for lingual deformation during the propulsive phase of swallowing as determined by phase-contrast magnetic resonance imaging SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE tongue; lingual deformation ID BOVINE TONGUE; FIBER ARCHITECTURE; IN-VIVO; DIFFUSION; MRI; MYOARCHITECTURE; PHARYNGEAL; MOVEMENT; STRAIN; MUSCLE AB The tongue is an intricately configured muscular or-an that undergoes a series of rapid shape changes intended to first configure and then transport the bolus from the oral cavity to the pharynx during swallowing. To assess the complex array of mechanical events occurring during the propulsive phase of swallowing. we employed tongue pressure-gated phase-contrast MRI to represent the tissue's local strain rate vectors. Validation of the capacity of phase-contrast MRI to represent local compressive and expansive strain rate was obtained by assessing deformation patterns induced by a synchronized mechanical plunger apparatus in a gelatinous material phantom. Physiological strain rate data were acquired in the sagittal and coronal orientations at 0, 200, 400, and 600 ms relative to the gating pulse during 2.5-ml water bolus swallows. This method demonstrated that the propulsive phase of swallowing is associated with a precisely organized series of compressive and expansive strain rate events. At the initiation of propulsion, bolus position resulted from obliquely aligned compressive and expansive strain. vertically aligned compressive strain and orthogonal expansion, and compressive strain aligned obliquely to the styloid process. Bolus reconfiguration and translocation resulted from a combination of compressive strain occurring in the middle and posterior tongue aligned obliquely between the anterior-inferior and the posterior-superior regions with commensurate orthogonal expansion, along with bidirectional contraction in the distribution of the transversus and verticalis muscle fibers. These data support the concept that propulsive lingual deformation is due to complex muscular interactions involving both extrinsic and intrinsic muscles. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu NR 39 TC 14 Z9 14 U1 0 U2 4 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 JUL PY 2007 VL 103 IS 1 BP 255 EP 265 DI 10.1152/japplphysiol.01070.2006 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KK UT WOS:000248410900035 PM 17395759 ER PT J AU Kramer, HF Goodyear, LJ AF Kramer, Henning F. Goodyear, Laurie J. TI Exercise, MAPK, and NF-kappa B signaling in skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE metabolism; contraction; inflammation; stress; diabetes ID ACTIVATED PROTEIN-KINASE; JUN NH2-TERMINAL KINASE; STIMULATED GLUCOSE-UPTAKE; P38 MAPK; INSULIN-RESISTANCE; GENE-EXPRESSION; OXIDATIVE STRESS; FA UPTAKE; DIFFERENTIAL REGULATION; TRANSCRIPTION FACTORS AB Mitogen-activated protein kinases (MAPKs) and NF-kappa B are two major regulators of gene transcription and metabolism in response to oxidative, energetic, and mechanical stress in skeletal muscle. Chronic activation of these signaling pathways has been implicated in the development and perpetuation of various pathologies, such as diabetes and cachexia. However, both MAPK and NF-kappa B are also stimulated by exercise, which promotes improvements in fuel homeostasis and can prevent skeletal muscle atrophy. This review will first discuss the major MAPK signaling modules in skeletal muscle, their differential activation by exercise, and speculated functions on acute substrate metabolism and exercise-induced gene expression. Focus will then shift to examination of the NF-kappa B pathway, including its mechanism of activation by cellular stress and its putative mediation of exercise-stimulated adaptations in antioxidant status, tissue regeneration, and metabolism. Although limited, there is additional evidence to suggest cross talk between MAPK and NF-kappa B signals with exercise. The objectives herein are twofold: 1) to determine how and why exercise activates MAPK and NF-kappa B; and 2) to resolve their paradoxical activation during diseased and healthy conditions. C1 Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu NR 100 TC 152 Z9 165 U1 4 U2 15 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 JUL PY 2007 VL 103 IS 1 BP 388 EP 395 DI 10.1152/japplphysiol.00085.2007 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KK UT WOS:000248410900051 PM 17303713 ER PT J AU Jain, S Goldberg, MB AF Jain, Sumita Goldberg, Marcia B. TI Requirement for YaeT in the outer membrane assembly of autotransporter proteins SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SHIGELLA-FLEXNERI; POLAR LOCALIZATION; OMP85 FAMILY; ICSA; SECRETION; IDENTIFICATION; EXPRESSION; DETERMINANTS; BIOGENESIS AB Autotransporters constitute the largest group of secreted proteins in gram-negative bacteria. Autotransporter secretion involves the insertion of a carboxy-terminal beta barrel into and the translocation of an amino-terminal domain across the outer membrane. Here, we demonstrate that secretion of autotransporters from several organisms requires the outer membrane assembly factor YaeT. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, Cambridge, MA USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, 65 Landsdowne St, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [AI061073, AI35817, R01 AI035817, R21 AI061073] NR 30 TC 74 Z9 75 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2007 VL 189 IS 14 BP 5393 EP 5398 DI 10.1128/JB.00228-07 PG 6 WC Microbiology SC Microbiology GA 189WQ UT WOS:000248019700045 PM 17513479 ER PT J AU Eisen, SV Ranganathan, G Seal, P Spiro, A AF Eisen, Susan V. Ranganathan, Gayatri Seal, Pradipta Spiro, Avron, III TI Measuring clinically meaningful change following mental health treatment SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; STATISTICAL SIGNIFICANCE; INTRAINDIVIDUAL CHANGES; ASSESSMENT INSTRUMENTS; GLOBAL ASSESSMENT; FUNCTIONING GAF; VALIDITY; RELIABILITY; BEHAVIOR; OUTCOMES AB Assessment of clinically meaningful change is useful for treatment planning, monitoring progress, and evaluating treatment response. Outcome studies often assess statistically significant change, which may not be clinically meaningful. Study objectives are to: (1) evaluate responsiveness of the BASIS-24 (c) using three methods for determining clinically meaningful change: reliable change index (RCI), effect size (ES), and standard error of measurement (SEM); and (2) determine which method provides an estimate of clinically meaningful change most concordant with other change measures. BASIS-24 (c) assessments were obtained at two time points for 1,397 inpatients and 850 outpatients. The proportion showing clinically meaningful change using each method was compared to the proportion showing change in global mental health, retrospectively reported change, and clinician-assessed change. BASIS-24 (c) demonstrated responsiveness at both aggregate and individual levels. Regarding clinically meaningful improvement and decline, SEM was most concordant with all three outcome measures; regarding no change, RCI was most concordant with all three measures. C1 Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. MetaWorks Inc, Boston, MA 02215 USA. Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA 01730 USA. VA Boston Healthcare Syst, Massachussetts Veterans Epidemiol Res & Informat, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Eisen, SV (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Springs Rd 152, Bedford, MA 01730 USA. EM seisen@bu.edu; gayatrir@bu.edu; pseal@math.bu.edu; ASpiro3@bu.edu OI Spiro III, Avron/0000-0003-4080-8621 FU NIMH NIH HHS [R01 MH58240] NR 50 TC 37 Z9 38 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JUL PY 2007 VL 34 IS 3 BP 272 EP 289 DI 10.1007/s11414-007-9066-2 PG 18 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 207BC UT WOS:000249225600004 PM 17534718 ER PT J AU Mujat, M Park, BH Cense, B Chen, TC de Boer, JF AF Mujat, Mircea Park, B. Hyle Cense, Barry Chen, Teresa C. de Boer, Johannes F. TI Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE ophthalmology; optical coherence tomography (OCT); birefringence; polarization ID HIGH-SPEED; ULTRAHIGH-RESOLUTION; THICKNESS; INTERFEROMETRY; TISSUE AB Accurate wavelength assignment of each spectral element for spectral-domain optical coherence tomography (SD-OCT) and optical frequency domain imaging (OFDI) is required for proper construction of biological tissue cross-sectional images. This becomes more critical for functional extensions of these techniques, especially in polarization-sensitive optical coherence tomography (PS-OCT), where incorrect wavelength assignment between the two orthogonal polarization channels leads to polarization artifacts. We present an autocalibration method for wavelength assignment that does not require separate calibration measurements and that can be applied directly on actual data. Removal of the birefringence artifact is demonstrated in a PS-OCT system with picometer accuracy in the relative wavelength assignment, resulting in a residual phase error of 0.25 deg/ 100 mu m. We also demonstrate, for the first time, a quantitative birefringence map of an in vivo human retinal nerve fiber layer. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard Med Sch, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. RP de Boer, JF (reprint author), Indiana Univ, Sch Optometry, 800 E Atwater Ave, Bloomington, IN 47408 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCRR NIH HHS [RR019768]; NEI NIH HHS [R01 EY014975] NR 25 TC 68 Z9 68 U1 0 U2 4 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2007 VL 12 IS 4 AR 041205 DI 10.1117/1.2764460 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 219HM UT WOS:000250075400006 PM 17867794 ER PT J AU Zhang, Q Brown, EN Strangman, GE AF Zhang, Quan Brown, Emery N. Strangman, Gary E. TI Adaptive filtering for global interference cancellation and real-time recovery of evoked brain activity: a Monte Carlo simulation study SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near-infrared spectroscopy; brain; neuronal; hemodynamics; Monte Carlo; adaptive filter; interference; cancellation ID NEAR-INFRARED SPECTROSCOPY; ADULT HEAD MODEL; CEREBRAL HEMODYNAMICS; OXYGENATION CHANGES; OPTICAL SPECTROSCOPY; PHOTON MIGRATION; FOCAL CHANGES; MOTOR-CORTEX; SIGNAL; LIGHT AB The sensitivity of near-infrared spectroscopy (NIRS) to evoked brain activity is reduced by physiological interference in at least two locations: 1. the superficial scalp and skull layers, and 2. in brain tissue itself. These interferences are generally termed as "global interferences" or "systemic interferences," and arise from cardiac activity, respiration, and other homeostatic processes. We present a novel method for global interference reduction and real-time recovery of evoked brain activity, based on the combination of a multiseparation probe configuration and adaptive filtering. Monte Carlo simulations demonstrate that this method can be effective in reducing the global interference and recovering otherwise obscured evoked brain activity. We also demonstrate that the physiological interference in the superficial layers is the major component of global interference. Thus, a measurement of superficial layer hemodynamics (e. g., using a short source-detector separation) makes a good reference in adaptive interference cancellation. The adaptive-filtering-based algorithm is shown to be resistant to errors in source-detector position information as well as to errors in the differential pathlength factor (DPF). The technique can be performed in real time, an important feature required for applications such as brain activity localization, biofeedback, and potential neuroprosthetic devices. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, Harvard Med Sch, Neural Syst Grp, Charlestown, MA 02129 USA. MIT, Massachusetts Gen Hosp, Harvard MIT Div Hlth Sci & Technol, Dept Anesthesia & Crit Care Dept Brain & Cognit S, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Harvard Med Sch, Neural Syst Grp, Charlestown, MA 02129 USA. RP Zhang, Q (reprint author), Harvard Med Sch, Neural Syst Grp, MGH 13th St,Bldg 149,Rm 2651, Charlestown, MA 02129 USA. EM qzhang@nmr.mgh.harvard.edu FU NIBIB NIH HHS [R21-EB02416]; NINDS NIH HHS [K25-NS46554] NR 46 TC 66 Z9 68 U1 1 U2 6 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2007 VL 12 IS 4 AR 044014 DI 10.1117/1.2754714 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 219HM UT WOS:000250075400030 PM 17867818 ER PT J AU Doornberg, JN van Duijn, PJ Linzel, D Ring, DC Zurakowski, D Marti, RK Kloen, P AF Doornberg, Job N. van Duijn, Pleun J. Linzel, Durk Ring, David C. Zurakowski, David Marti, Rene K. Kloen, Peter TI Surgical treatment of intra-articular fractures of the distal part of the humerus SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID COMPLEX FRACTURES; ELBOW FUNCTION; FIXATION; ADULTS AB Background: The short-term results of open reduction and internal fixation of intra-articular distal humeral fractures are good to excellent in approximately 75% of patients, but the long-term results have been less well studied. This investigation addressed the long-term clinical and radiographic results of surgical treatment of intra-articular distal humeral fractures (AO Type C) as assessed with use of standardized outcome measures. Methods: Thirty patients were evaluated at an average of nineteen years (range, twelve to thirty years) after open reduction and internal fixation of a fracture of the distal part of the humerus to assess the range of elbow motion and the functional outcome. Twenty patients had an olecranon osteotomy, and all had fixation with plates and/or screws and/or Kirschner wires. No ulnar nerve was transposed. Results: Excluding one elbow salvaged with an arthrodesis and counted as a poor result, the average final flexion arc was 1060 and the average pronation-supination arc was 165 degrees. The average American Shoulder and Elbow Surgeons (ASES) score was 96 points, with an average satisfaction score of 8.8 points on a 0 to 10-point visual analog scale. The average Disabilities of the Arm, Shoulder and Hand (DASH) score was 7 points, and the average Mayo Elbow Performance Index (MEPI) score was 91 points. Including the patient with the arthrodesis, the final categorical ratings were nineteen excellent results, seven good results, one fair result, and three poor results. The presence of arthrosis did not appear to correlate with pain or predict disability or function. Subsequent procedures were performed in twelve patients (40%). Conclusions: The long-term results of open reduction and internal fixation of AO-Type-C fractures of the distal part of the humerus are similar to those reported in the short term, suggesting that the results are durable. Functional ratings and perceived disability were predicated more on pain than on functional impairment and did not correlate with radiographic signs of arthrosis. C1 Acad Med Ctr, Orthotrauma Res Ctr Amsterdam, NL-1100 DD Amsterdam, Netherlands. Acad Med Ctr, Dept Orthopaed Surg, NL-1100 DD Amsterdam, Netherlands. Massachusetts Gen Hosp, Orthopaed Hand & Upper Exterm Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Doornberg, JN (reprint author), Acad Med Ctr, Orthotrauma Res Ctr Amsterdam, G4 Noord,Kamer 249,Meibergdeef 9, NL-1100 DD Amsterdam, Netherlands. EM jdoornberg@partners.org NR 24 TC 53 Z9 58 U1 1 U2 4 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 JUL PY 2007 VL 89A IS 7 BP 1524 EP 1532 DI 10.2106/JBJS.F.00369 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 187ZF UT WOS:000247887300017 PM 17606792 ER PT J AU Monica, JT Kwolek, CJ Jupiter, JB AF Monica, James T. Kwolek, Christopher J. Jupiter, Jesse B. TI Thoracic outlet syndrome with subclavian artery thrombosis undetectable by magnetic resonance angiography SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID 3-DIMENSIONAL MR-ANGIOGRAPHY; AXILLARY ARTERY; 1ST RIB; DISLOCATION C1 Massachusetts Gen Hosp, Orthopaed Teaching Off, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Monica, JT (reprint author), Massachusetts Gen Hosp, Orthopaed Teaching Off, GRB 622,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 2007 VL 89A IS 7 BP 1589 EP 1593 DI 10.2106/JBJS.F.01253 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 187ZF UT WOS:000247887300024 PM 17606799 ER PT J AU Nield, MA Hoo, GWS Roper, JM Santiago, S AF Nield, Margaret A. Hoo, Guy W. Soo Roper, Janice M. Santiago, Silverio TI Efficacy of pursed-lips breathing - A breathing pattern retraining strategy for dyspnea reduction SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE breathing exercises; chronic obstructive; dyspnea; pulmonary disease ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW LIMITATION; HEALTH SURVEY SF-36; QUALITY-OF-LIFE; RESPIRATORY SENSATION; BREATHLESSNESS; EXERCISE; COPD; HYPERINFLATION; MANAGEMENT AB PURPOSE: Breathing pattern retraining is frequently used for exertional dyspnea relief in adults with moderate to severe chronic obstructive pulmonary disease. However, there is contradictory evidence to support its use. The study objective was to compare 2 programs of prolonging expiratory time (pursed-lips breathing and expiratory muscle training) on dyspnea and functional performance. METHODS: A randomized, controlled design was used for the pilot study. Subjects recruited from the outpatient pulmonary clinic of a university-affiliated Veteran Affairs healthcare center were randomized to: 1) pursed-lips breathing, 2) expiratory muscle training, or 3) control. Changes over time in dyspnea [modified Borg after 6-minute walk distance (6MWD) and Shortness of Breath Questionnaire] and functional performance (Human Activity Profile and physical function scale of Short Form 36-item Health Survey) were assessed with a multilevel modeling procedure. Weekly laboratory visits for training were accompanied by structured verbal, written, and audiovisual instruction. RESULTS: Forty subjects with chronic obstructive pulmonary disease [age = 65 +/- 9 (mean +/- standard deviation) years, forced expiratory volume 1 second/ forced vital capacity % = 46 +/- 10, forced expiratory volume 1 second % predicted = 39 +/- 13, body mass index = 26 +/- 6 kg/M-2, inspiratory muscle strength = 69 +/- 22 cm H2O, and expiratory muscle strength (PEmax) = 102 +/- 29 cm H2O] were enrolled. No significant Group x Time difference was present for PEmax (P = .93). Significant reductions for the modified Borg scale after 6MWD (P = .05) and physical function (P = .02) from baseline to 12 weeks were only present for pursed-lips breathing. CONCLUSION: Pursed-lips breathing provided sustained improvement in exertional dyspnea and physical function. C1 Univ Hawaii Manoa, Honolulu, HI 96822 USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. RP Nield, MA (reprint author), Univ Hawaii Manoa, 2528 McCarthy Mall,Webster 414, Honolulu, HI 96822 USA. EM mnield@earthlink.net NR 34 TC 37 Z9 39 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-7501 J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD JUL-AUG PY 2007 VL 27 IS 4 BP 237 EP 244 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 200AO UT WOS:000248736500009 PM 17667021 ER PT J AU Carroll, DL Rankin, SH Cooper, BA AF Carroll, Diane L. Rankin, Sally H. Cooper, Bruce A. TI The effects of a collaborative peer advisor/advanced practice nurse intervention - Cardiac rehabilitation participation and rehospitalization in older adults after a cardiac event SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE advanced practice nurse; aged; cardiac rehabilitation; peer counseling ID EXAMPLE AB Background: After the cardiovascular events of myocardial infarction (MI) and coronary artery bypass surgery (CABS), unpartnered older adults are a vulnerable group that may benefit from interventions to improve health outcomes. The purpose of this analysis is to determine if a community-based collaborative peer advisor/advanced practice nurse intervention increased participation in cardiac rehabilitation programs and reduced hospital readmissions after MI and CABS and determine whether the type of cardiovascular event influenced rehospitalization. Subjects and Methods: This study was a randomized clinical trial that enrolled 247 unpartnered older adults who were single, widowed, or divorced. Subjects were randomized into 4 groups: standard of care group for MI and for CABS and standard of care plus the treatment groups for MI and for CABS, for 12 weeks after discharge. There were 163 women/84 men, with a mean age of 76.4 years, who were admitted for MI (n = 93) or CABS (n = 154) and who were enrolled from 5 academic medical centers. The treatment consisted of a community-based intervention of a home visit within 72 hours and telephone calls at 2, 6, and 10 weeks from an advanced practice nurse and 12 weekly telephone calls from a peer advisor. Participation in a cardiac rehabilitation program and rehospitalizations were collected at 6 weeks and 3, 6, and 12 months by telephone interview. Results and Conclusions: There were significantly more participants in cardiac rehabilitation programs after 3 months in the treatment group, and this increase was seen up to 1 year after MI and CABS. There were no statistical differences, although there were fewer rehospitalizations between 3 and 6 months after MI and CABS in the treatment group compared with the standard of care group. Overall, the evidence from this study suggests that a community-based collaborative peer advisor/advanced practice nurse intervention can play a role in promoting active participation in cardiac rehabilitation programs and fewer rehospitalizations in unpartnered older adults after MI and CAGS. C1 Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Inst Patient Care, Boston, MA 02114 USA. Univ Calif San Francisco, Sch Nursing, Res Off, San Francisco, CA 94143 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Inst Patient Care, POB 429, Boston, MA 02114 USA. EM dcarroll3@partners.org FU NINR NIH HHS [R01 NR05205] NR 27 TC 37 Z9 38 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD JUL-AUG PY 2007 VL 22 IS 4 BP 313 EP 319 PG 7 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 184TZ UT WOS:000247666800009 PM 17589284 ER PT J AU de la Cruz, J Behlau, I Pineda, R AF de la Cruz, Jose Behlau, Irmgard Pineda, Roberto TI Atypical mycobacteria keratitis after laser in situ keratomileusis unresponsive to fourth-generation fluoroquinolone therapy SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; CHELONAE KERATITIS; LASIK; CIPROFLOXACIN; FORTUITUM AB We report a case of post-laser in situ keratomileusis atypical mycobacteria infection unresponsive and resistant to fourth-generation fluoroquinolones, which highlights the importance of a high level of suspicion and the need for multidrug therapy for effective eradication. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Infect Dis Serv, Boston, MA 02114 USA. RP Pineda, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM rpineda@partners.org RI de la Cruz, Jose/A-1994-2010 NR 23 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 2007 VL 33 IS 7 BP 1318 EP 1321 DI 10.1016/j.jcrs.2007.03.035 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 188VU UT WOS:000247948200037 PM 17586393 ER PT J AU Chu, GC Kimmelman, AC Hezel, AF DePinho, RA AF Chu, Gerald C. Kimmelman, Alec C. Hezel, Aram F. DePinho, Ronald A. TI Stromal biology of pancreatic cancer SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Review DE pancreatic cancer; tumor stroma; pancreatic ductal adenocarcinoma; tumor microenvironment ID FACTOR-BETA RECEPTOR; HEPATOCYTE GROWTH-FACTOR; NF-KAPPA-B; TRANSGENIC MOUSE MODEL; STELLATE CELLS; DUCTAL ADENOCARCINOMA; GENE-EXPRESSION; TGF-BETA; INTRAEPITHELIAL NEOPLASIA; TUMOR-STROMA AB The genetic paradigm of cancer, focused largely on sequential molecular aberrations and associated biological impact in the neoplastic cell compartment of malignant tumors, has dominated Our view of cancer pathogenesis. For the most part, this conceptualization has overlooked the dynamic and complex contributions of the surrounding microenvironment comprised of non-tumor cells (stroma) that may resist, react to, and/or foster tumor development. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease in which a prominent tumor stroma compartment is a defining characteristic. Indeed, the bulk of PDAC tumor volume consists of non-neoplastic fibroblastic, vascular, and inflammatory cells surrounded by immense quantities of extracellular matrix, far exceeding that found in most other tumor types. Remarkably, little is known about the composition and physiology of the PDAC tumor microenvironment, in particular, the role of stroma in tumor initiation and progression. This review attempts to define key challenges, opportunities and state-of-know relating to the PDAC microenvironment research with an emphasis on how inflammatory processes and key cancer pathways may shape the ontogeny of the tumor stroma. Such knowledge may be used to understand the evolution and biology of this lethal cancer and may convert these insights into new points of therapeutic intervention. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Radiat Oncol Program, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Ron_depinho@dfci.harvard.edu FU NCI NIH HHS [U01 CA84313-07, K08 CA122835, P01 CA117969-01] NR 152 TC 142 Z9 144 U1 7 U2 28 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2007 VL 101 IS 4 BP 887 EP 907 DI 10.1002/jcb.21209 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185EQ UT WOS:000247694600009 PM 17266048 ER PT J AU Fukumura, D Jain, RK AF Fukumura, Dai Jain, Rakesh K. TI Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE microenvironment; hypoxia; acidosis; interstitial fluid pressure; angiogenesis; microcircualtion; lymphangiogenesis; lymphatic metastasis; stromal cells; vascular endothelial growth factor; intravital microscopy ID ENDOTHELIAL GROWTH-FACTOR; INTERSTITIAL FLUID PRESSURE; RECTAL-CANCER PATIENTS; SOLID TUMORS; IN-VIVO; ANTIANGIOGENIC THERAPY; VASCULAR-PERMEABILITY; BLOOD-FLOW; DRUG-DELIVERY; FACTOR VEGF AB A solid tumor is an organ-like entity comprised of neoplastic cells and non-transformed host stromal cells embedded in an extracellular matrix. The expression of various genes is influenced by interactions among these cells, surrounding matrix, and their local physical and biochemical microenvironment. The products encoded by these genes, in turn, control the pathophysiological characteristics of the tumor, and give rise to the abnormal organization, structure, and function of tumor blood vessels. These abnormalities contribute to heterogeneous blood flow, vascular permeability, and microenvironment. Proliferating tumor cells produce solid stress which compresses blood and lymphatic vessels. As a result of vessel leakiness and lack of functional lymphatics, interstitial fluid pressure is significantly elevated in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, the metabolic microenvironment in tumors such as hypoxia and acidosis hinder the efficacy of anti-tumor treatments such as radiation therapy and chemotherapy. A judicious application of anti-angiogenic therapy has the potential to overcome these problems by normalizing the tumor vessels and making them more efficient for delivery of oxygen and drugs. Combined anti-angiogenic and conventional therapies have shown promise in the clinic. C1 Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu FU NCI NIH HHS [R01 CA85140, P01 CA80124, R01 CA115767-01, R01 CA96915, U01 CA084301] NR 78 TC 245 Z9 258 U1 3 U2 51 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2007 VL 101 IS 4 BP 937 EP 949 DI 10.1002/jcb.21187 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185EQ UT WOS:000247694600013 PM 17171643 ER PT J AU Mitsiades, CS Mitsiades, NS Richardson, PG Munshi, NC Anderson, KC AF Mitsiades, Constantine S. Mitsiades, Nicholas S. Richardson, Paul G. Munshi, Nikhil C. Anderson, Kenneth C. TI Multiple myeloma: A prototypic disease model for the characterization and therapeutic targeting of interactions between tumor cells and their local microenvironment SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Review DE multiple myeloma; bone microenvironment; cytokines ID GROWTH-FACTOR-I; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; COLONY-STIMULATING FACTOR; MEDIATED DRUG-RESISTANCE; HUMAN-BONE-MARROW; BCL-X-L; THALIDOMIDE PLUS DEXAMETHASONE; FARNESYL TRANSFERASE INHIBITOR; HISTONE DEACETYLASE INHIBITION AB The interaction between tumor cells and the local milieu where are homing has recently become the focus of extensive research in a broad range of malignancies. Among them, multiple myeloma (MM) is now recognized as a Prototypical tumor model for the characterization of these interactions. This is due not only to the propensity of MM cells to target the skeleton and form lytic bone lesions, but because interactions of MM cells with normal cells of the bone milieu can attenuate the anti-tumor activity of conventional therapies, such as glucocorticoids and standard cytotoxic agents, including alkylators. Herein,we highlight the recent advances in our understanding of cellular and molecular mechanisms of interactions between MM cells and their milieu. Particular emphasis is placed on the interface between MM cells and normal cell compartments of the BM, especially bone marrow stromal cells (BMSCs), and on the development of a series of new classes of therapeutic agents, including the proteasome inhibitor bortezomib, thalidomide and lenalidomide, which counteract specific aspects of those MM-BM interactions. The significant clinical activity of these novel therapies has not only led to a new era in the therapeutic management of this disease, but also underscored the importance of comprehensively characterizing the role of the local microenvironment in the pathophysiology of human neoplasias. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dept Med, 44 Binney St, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu NR 176 TC 50 Z9 52 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2007 VL 101 IS 4 BP 950 EP 968 DI 10.1002/jcb.21213 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185EQ UT WOS:000247694600014 PM 17546631 ER PT J AU Hayashi, C Rittling, S Hayata, T Amagasa, T Denhardt, D Ezura, Y Nakashima, K Noda, M AF Hayashi, Chikako Rittling, Susan Hayata, Taclayoshi Amagasa, Teruo Denhardt, David Ezura, Yoichi Nakashima, Kazuhisa Noda, Masaki TI Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE osteopontin; melanoma; migration; metastasis; bone ID PLASMINOGEN-ACTIVATOR EXPRESSION; COMPLEMENT-MEDIATED ATTACK; BREAST-CANCER CELLS; SECRETED PHOSPHOPROTEIN; PLASMA OSTEOPONTIN; COMPONENT; SURVIVAL; MOTILITY; BINDING; EVASION AB Tumor malignancy is associated with several features Such as proliferation ability and frequency of metastasis. Since tumor metastasis shortens patients' lifetime, establishment of therapy for anti-metastasis is very important. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, extracellular matrix (ECM) invasion and cell proliferation via interaction with its receptor, that is, alpha v beta 3 integrin. OPN is believed to be a positive regulator of tumor metastasis in vivo. However, how OPN regulates metastasis is largely unknown. Here, we explore the role of OPN in cell migration. Serum from wild-type mice induced cell migration of B16 melanoma cells, while serum from OPN-deficient mouse suppressed this event. The presence of recombinant OPN significantly enhanced cell migration compared to albumin containing medium. OPN-induced cell migration was suppressed by inhibiting the ERK/MAPK pathway indicating that OPN-induced cell migration depends on this pathway. Overexpression of OPN in these cancer cells per se promoted cell proliferation and tended to increase B16 cell migration suggesting that OPN promotes bone metastasis by playing dual roles both in host microenvironment and in tumor cell itself. In conclusion, the elevated OPN expression in host tissue and tumor cell itself promotes tumor cell migration reading to tumor metastasis, suggesting that neutralization of OPN-induced signal might be effective in suppression of tumor metastasis. C1 Tokyo Med & Dent Univ, Dept Mol Pharmacol, Med Res Inst, Chiyoda Ku, Tokyo 1010062, Japan. Forsyth Inst, Boston, MA USA. Tokyo Med & Dent Univ, Dept Maxillofacial Surg, Tokyo 1010062, Japan. Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. Century Ctr Excellence 21, Program Frontier Res Mol Destruct & Reconstruct T, Tokyo, Japan. Tokyo Med & Dent Univ, Core Core Program, JSPS, Tokyo 1010062, Japan. Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 1010062, Japan. RP Ezura, Y (reprint author), Tokyo Med & Dent Univ, Dept Mol Pharmacol, Med Res Inst, Chiyoda Ku, 3-10 Kandasurugadai,2 Chome, Tokyo 1010062, Japan. EM ezura.mph@mri.tmd.ac.jp; noda.mph@mri.tmd.ac.jp RI Ezura, Yoichi/L-9485-2016 NR 27 TC 31 Z9 34 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2007 VL 101 IS 4 BP 979 EP 986 DI 10.1002/jcb.21298 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185EQ UT WOS:000247694600016 PM 17390343 ER PT J AU Antshel, KM Faraone, SV Stallone, K Nave, A Kaufmann, FA Doyle, A Fried, R Seidman, L Biederman, J AF Antshel, Kevin M. Faraone, Stephen V. Stallone, Kimberly Nave, Andrea Kaufmann, Felice A. Doyle, Alysa Fried, Ronna Seidman, Larry Biederman, Joseph TI Is attention deficit hyperactivity disorder a valid diagnosis in the presence of high IQ? Results from the MGH Longitudinal Family Studies of ADHD SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE intelligence; ADD; ADHD; gifted; diagnosis; diagnostic validity ID DEFICIT/HYPERACTIVITY DISORDER; DEVELOPMENTAL PATHWAYS; WISC-III; SELECTION; CHILDREN; SCORES; GIFTEDNESS; STUDENTS; AD/HD; BOYS AB Background: The aim of this study was to assess the validity of diagnosing attention deficit/hyperactivity disorder (ADHD) in high IQ children and to further characterize the clinical features associated with their ADHD. Methods: We operationalized giftedness/high IQ as having a full scale IQ >= 120. We identified 92 children with a high IQ who did not have ADHD and 49 children with a high IQ that met diagnostic criteria for ADHD who had participated in the Massachusetts General Hospital Longitudinal Family Studies of ADHD. Results: Of our participants with ADHD and a high IQ, the majority (n = 35) met criteria for the Combined subtype. Relative to control participants, children with ADHD and high IQ had a higher prevalence rate of familial ADHD in first-degree relatives, repeated grades more often, had a poorer performance on the WISC-III Block Design, had more comorbid psychopathology, and had more functional impairments across a number of domains. Conclusions: Children with a high IQ and ADHD showed a pattern of familiality as well as cognitive, psychiatric and behavioral features consistent with the diagnosis of ADHD in children with average IQ. These data suggest that the diagnosis of ADHD is valid among high IQ children. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. SUNY Upstate, Dept Psychiat & Behav Sci, Syracuse, NY USA. NYU, Ctr Child Study, New York, NY 10012 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, 15 Parkman St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 NR 54 TC 38 Z9 39 U1 2 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUL PY 2007 VL 48 IS 7 BP 687 EP 694 DI 10.1111/j.1469-7610.2007.01735.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 182AJ UT WOS:000247477200007 PM 17593149 ER PT J AU Miller, KK Biller, BMK Schaub, A Pulaski-Liebert, K Bradwin, G Rifai, N Klibanski, A AF Miller, K. K. Biller, B. M. K. Schaub, A. Pulaski-Liebert, K. Bradwin, G. Rifai, N. Klibanski, A. TI Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; SEXUAL DESIRE DISORDER; HOMEOSTASIS MODEL ASSESSMENT; SURGICALLY MENOPAUSAL WOMEN; TOTAL HOMOCYSTEINE LEVELS; CELL-ADHESION MOLECULE-1; CHOLESTEROL-FED RABBITS; C-REACTIVE PROTEIN; TERM-FOLLOW-UP; INSULIN SENSITIVITY AB Context: Low-dose testosterone replacement therapy in women with relative androgen deficiency has been shown to have beneficial effects on body composition, bone mass, and psychosexual function. However, the safety of chronic testosterone administration on cardiovascular risk and insulin resistance is unknown. Objective: The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women. Design: A 12-month, randomized, placebo-controlled study was conducted. Setting: A General Clinical Research Center was the setting for the study. Study Participants: A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated. Intervention: Study participants were randomized to physiological testosterone administration, 300 mu g daily, or placebo, by patch. Main Outcome Measures: We measured fasting glucose, fasting insulin, insulin- resistance homeostasis model of assessment (IRHOMA), quantitative insulin sensitivity check index (QUICKI), high-sensitivity C-reactive protein, vascular cell adhesion molecule (VCAM), leptin, lipoprotein (a), apolipoprotein A1, and homocysteine. Results: At 12 months, fasting insulin and IRHOMA were significantly lower in the testosterone compared with the placebo group, and there was a trend toward a higher QUICKI level at 12 months in the testosterone compared with the placebo group. These differences were no longer significant after controlling for baseline levels. We observed no effect, either positive or negative, of testosterone administration on high-sensitivity C-reactive protein, VCAM leptin, lipoprotein (a), or apolipoprotein A1. Conclusions: Our data suggest that physiological testosterone replacement in women with hypopituitarism for 12 months does not increase, and may improve, insulin resistance. Chronic low-dose testosterone administration does not increase markers of cardiovascular disease reflecting several different mechanistic pathways. Large, randomized, placebo-controlled, long-term prospective studies are needed to determine whether low-dose testosterone replacement affects cardiovascular risk and event rates in women. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU FDA HHS [FD-R-001981]; NCRR NIH HHS [M01 RR01066] NR 44 TC 20 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2007 VL 92 IS 7 BP 2474 EP 2479 DI 10.1210/jc.2007-0195 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187ME UT WOS:000247851000014 PM 17426086 ER PT J AU Triant, VA Lee, H Hadigan, C Grinspoon, SK AF Triant, Virginia A. Lee, Hang Hadigan, Colleen Grinspoon, Steven K. TI Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; HIV-INFECTED INDIVIDUALS; PROTEASE INHIBITORS; ANTIRETROVIRAL THERAPY; DIABETES-MELLITUS; LIPODYSTROPHY; ATHEROSCLEROSIS; HYPERLIPIDEMIA; PREVALENCE; PREDICTION AB Context: Metabolic changes and smoking are common among HIV patients and may confer increased cardiovascular risk. Objective: The aim of the study was to determine acute myocardial infarction (AMI) rates and cardiovascular risk factors in HIV compared with non-HIV patients in two tertiary care hospitals. Design, Setting, and Participants: We conducted a health care system-based cohort study using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients. AMI rates were determined among patients receiving longitudinal care between October 1, 1996, and June 30, 2004. Main Outcome Measures: The primary outcome was myocardial infarction, identified by International Classification of Diseases coding criteria. Results: AMI was identified in 189 HIV and 26,142 non-HIV patients. AMI rates per 1000 person-years were increased in HIV vs. non-HIV patients [11.13 (95% confidence interval [CI] 9.58-12.68) vs. 6.98 ( 95% CI 6.89-7.06)]. The HIV cohort had significantly higher proportions of hypertension (21.2 vs. 15.9%), diabetes (11.5 vs. 6.6%), and dyslipidemia (23.3 vs. 17.6%) than the non-HIV cohort (P < 0.0001 for each comparison). The difference in AMI rates between HIV and non-HIV patients was significant, with a relative risk (RR) of 1.75 (95% CI 1.51-2.02; P < 0.0001), adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. In gender-stratified models, the unadjusted AMI rates per 1000 person-years were higher for HIV patients among women (12.71 vs. 4.88 for HIV compared with non-HIV women), but not among men (10.48 vs. 11.44 for HIV compared with non-HIV men). The RRs (for HIV vs. non-HIV) were 2.98 (95% CI 2.33-3.75; P < 0.0001) for women and 1.40 (95% CI 1.16-1.67; P = 0.0003) for men, adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. A limitation of this database is that it contains incomplete data on smoking. Smoking could not be included in the overall regression model, and some of the increased risk may be accounted for by differences in smoking rates. Conclusions: AMI rates and cardiovascular risk factors were increased in HIV compared with non-HIV patients, particularly among women. Cardiac risk modification strategies are important for the long-term care of HIV patients. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,Longfellow 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [RR-01066, M01 RR001066]; NIAID NIH HHS [K01 AI073109, K01 AI073109-01A1, T32 AI007387]; NIDDK NIH HHS [DK-49302, DK-59535, R01 DK049302, R01 DK059535] NR 26 TC 620 Z9 632 U1 1 U2 27 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 JUL PY 2007 VL 92 IS 7 BP 2506 EP 2512 DI 10.1210/jc.2006-2190 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187ME UT WOS:000247851000019 PM 17456578 ER PT J AU Brabant, G Rasmussen, AK Biller, BMK Buchfelder, M Feldt-Rasmussen, U Forssmann, K Jonsson, B Koltowska-Haggstrom, M Maiter, D Saller, B Toogood, A AF Brabant, Georg Rasmussen, Ase Krogh Biller, Beverly M. K. Buchfelder, Michael Feldt-Rasmussen, Ulla Forssmann, Kristin Jonsson, Bjorn Koltowska-Haggstrom, Maria Maiter, Dominique Saller, Bernhard Toogood, Andy TI Clinical implications of residual growth hormone (GH) response to provocative testing in adults with severe GH deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOPITUITARY PATIENTS; HEALTHY-ADULTS; DIAGNOSIS; REPLACEMENT; DISEASE; AGE; CHOLESTEROL; SENSITIVITY; ARGININE; FITNESS AB Context: The diagnosis of GH deficiency ( GHD) in adults is based on provocative tests of GH release, all influenced by clinical factors. It is unknown whether the amount of residual GH reserve under the cutoff value has any physiological implication. Objectives: We used a large pharmacoepidemiological database of adult GHD (KIMS) and tested the impact of confounding factors on GH release of no greater than 3 mu g/liter after an insulin tolerance test ( ITT) and evaluated its potential physiological role. Design, Settings, and Patients: A total of 1098 patients fulfilled the criteria of having a GH peak of no greater than 3 mu g/liter during ITT as well as documented IGF-I levels. Outcomes: The impact of underlying hypothalamic-pituitary disease, age, gender, body weight, as well as treatment modalities such as irradiation on peak GH level to ITT was evaluated, and the correlations between GH peak and targets of GH action were analyzed. Results: The GH response to ITT was regulated by gender, age, and the number of additional pituitary deficiencies. In a multivariate evaluation, the extent of hypothalamic-pituitary dysfunction was the most important single predictor of GH peak in ITT. GH peaks in ITT were positively related to IGF-I levels and high-density lipoprotein-cholesterol, as well as inversely to triglycerides. Conclusions: Even in adult severe GHD, GH release appears to be regulated by factors defined to play an important role in normal GH secretion. The impact of very low GH release on IGF-I and lipid parameters indicates a persistent physiological role of low GH concentrations in severely affected patients with GHD. C1 Christie Hosp NHS Trust, Dept Endocrinol, Manchester M20 4BX, Lancs, England. Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Neurosurg, D-91045 Erlangen, Germany. Pfizer GmbH, Dept Med, D-76139 Karlsruhe, Germany. Univ Uppsala, Dept Womens & Childrens Hlth, S-75105 Uppsala, Sweden. Univ Uppsala, Dept Pharm, S-75105 Uppsala, Sweden. Pfizer Hlth AB, KIGS KIMS, ACROSTUDY Med Outcomes, S-19091 Sollentuna, Sweden. Univ Hosp St Luc, Dept Endocrinol, B-1200 Brussels, Belgium. EndoScience, D-80337 Munich, Germany. Univ Hosp Natl Hlth Serv Fdn Trust, Dept Endocrinol, Birmingham B15 2TH, W Midlands, England. RP Brabant, G (reprint author), Christie Hosp NHS Trust, Dept Endocrinol, Wilmslow Rd, Manchester M20 4BX, Lancs, England. EM georg.brabant@manchester.ac.uk NR 31 TC 18 Z9 19 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2007 VL 92 IS 7 BP 2604 EP 2609 DI 10.1210/jc.2007-0153 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187ME UT WOS:000247851000033 PM 17488801 ER PT J AU Plengvidhya, N Kooptiwut, S Songtawee, N Doi, A Furuta, H Nishi, M Nanjo, K Tantibhedhyangkul, W Boonyasrisawat, W Yenchitsomanus, PT Doria, A Banchuin, N AF Plengvidhya, Nattachet Kooptiwut, Suwattanee Songtawee, Napat Doi, Asako Furuta, Hiroto Nishi, Masahiro Nanjo, Kishio Tantibhedhyangkul, Wiwit Boonyasrisawat, Watip Yenchitsomanus, Pa-Thai Doria, Alessandro Banchuin, Napatawn TI PAX4 mutations in Thais with maturity onset diabetes of the young SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PANCREATIC DEVELOPMENT; ALPHA-GENE; MODY GENES; MELLITUS; DIFFERENTIATION; GLUCOKINASE; JAPANESE AB Context: Six maturity onset diabetes of the young ( MODY) genes have been discovered to date but account for a small proportion of MODY among Asians, suggesting the existence of other MODY genes in this racial group. Objective: The aim of this study was to investigate whether or not genetic variants in PAX4, a crucial transcription factor in beta-cell development, contribute to MODY in Thais. Design and Methods: We screened PAX4 coding sequences in 46 MODY probands without mutation in known MODY genes and in 74 nondiabetic controls using PCR-single-stranded conformational polymorphism analysis followed by direct sequencing. Genotyping of variants identified was done by PCR-restriction fragment length polymorphism analysis. Results: Eight sequence differences were identified. Two novel variations (R164W and IVS7-1G > A) were found in two different probands. Neither was found in the 74 nondiabetic controls and additional 270 healthy subjects of Thai origin. R164W segregated with diabetes in the family of the proband and in vitro studies showed that it impairs the repressor activity of PAX4 on the insulin and glucagon promoters. The remaining six variants were previously described and observed in both groups. One of them, R192H, was three times more frequent in MODY probands than in 342 nondiabetic controls ( minor allele frequency = 0.196 vs. 0.064; P < 0.00001). The same variant was associated with a younger age at diagnosis among 254 Thai subjects with adult-onset type 2 diabetes (44.6 +/- 15 vs. 49.7 +/- 11 yr; P = 0.048). Conclusions: We have identified two possible pathogenic mutations of PAX4, R164W, and IVS7-1G > A. For one of these, we have shown evidence of segregation with diabetes and a functional impact on PAX4 activity. Single-nucleotide polymorphism R192H might influence the age at onset of diabetes. C1 Mahidol Univ, Fac Med, Siriraj Hosp, Dept Med,Div Endocrinol & Metab, Bangkok 10700, Thailand. Mahidol Univ, Fac Med, Siriraj Hosp, Dept Immunol, Bangkok 10700, Thailand. Mahidol Univ, Fac Med, Siriraj Hosp, Grad Program Immunol, Bangkok 10700, Thailand. Mahidol Univ, Fac Med, Siriraj Hosp, Dept Physiol, Bangkok 10700, Thailand. Mahidol Univ, Fac Med, Siriraj Hosp, Dept Res & Dev, Bangkok 10700, Thailand. Wakayama Med Univ, Dept Med 1, Wakayama 6418509, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Plengvidhya, N (reprint author), Mahidol Univ, Fac Med, Siriraj Hosp, Dept Med,Div Endocrinol & Metab, Bangkok 10700, Thailand. EM sinpv.natpl@gmail.com FU NIDDK NIH HHS [DK55523, R01 DK055523-08, R01 DK055523] NR 18 TC 53 Z9 64 U1 0 U2 5 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 JUL PY 2007 VL 92 IS 7 BP 2821 EP 2826 DI 10.1210/jc.2006-1927 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187ME UT WOS:000247851000064 PM 17426099 ER PT J AU Hunt, RH Tytgat, GH Malfertheiner, P Fock, KM Heading, RC Katelaris, PH McCarthy, DM McColl, KEL Moss, SF Sachs, G Sontag, SJ Thomson, ABR Modlin, IM AF Hunt, Richard H. Tytgat, Guido H. Malfertheiner, Peter Fock, Kwong Ming Heading, Robert C. Katelaris, Peter H. McCarthy, Denis M. McColl, Kenneth E. L. Moss, Steven F. Sachs, George Sontag, Stephen J. Thomson, Alan B. R. Modlin, Irvin M. TI Whistler summary: "The slow rate of rapid progress" SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material ID GASTROESOPHAGEAL-REFLUX DISEASE; PROTON-PUMP INHIBITORS; ESOPHAGOGASTRIC JUNCTION; BARRETTS-ESOPHAGUS; ACID SUPPRESSION; QUESTIONNAIRE; ESOMEPRAZOLE; METAANALYSIS; DYSPEPSIA; CONSENSUS AB Gastroesophageal reflux disease (GERD) is now the most common diagnosis made in gastroenterology outpatient practice. Increasing time and resources are spent on its management each year. Many conditions associated with, or the result of, GERD also appear to be on the rise-the most worrisome, esophageal adenocarcinoma, is steadily increasing in incidence, although it remains an uncommon cancer. Now that proton pump inhibitors (PPIs) are widely available, including over the counter in some countries, patients seen in consultation by gastroenterologists are becoming ever more challenging. In view of these trends, a meeting was convened in Whistler, British Columbia, Canada, in the fall of 2006 to review the current state-of-the-art approach to GERD, and to highlight areas of uncertainty in this field. The aim was to focus attention on patient needs, in an effort to provide better symptomatic care. The discussions were free ranging, on a variety of the most difficult problems, and the chairmen were instructed to lead the discussions into the unmet needs. The following pages highlight a summary of these discussions. C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. McMaster Univ, Hlth Sci Ctr, Hamilton, ON, Canada. Univ Alberta, Edmonton, AB, Canada. Univ Amsterdam, Amsterdam, Netherlands. Univ Magdeburg, D-39106 Magdeburg, Germany. Changi Gen Hosp, Div Gastroenterol, Singapore, Singapore. Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland. Univ Sydney, Concord Hosp, Sydney, NSW 2006, Australia. Univ New Mexico, Albuquerque, NM 87131 USA. USAF, Vet Affairs Med Ctr, Albuquerque, NM USA. Western Infirm & Associated Hosp, Glasgow, Lanark, Scotland. Rhode Isl Hosp, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Vet Affairs Hosp, Hines, IL USA. RP Modlin, IM (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. EM imodlin@optonline.net NR 28 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JUL PY 2007 VL 41 IS 6 BP 539 EP 545 DI 10.1097/MCG.0b013e31803d0fd8 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187FU UT WOS:000247833800001 PM 17577108 ER PT J AU Hunt, RH Tytgat, GN Malfertheiner, P Fock, KM Heading, RC Katelaris, PH McCarthy, DM McColl, KE Moss, SF Sachs, G Sontag, SJ Thomson, ABR Modlin, IM AF Hunt, Richard H. Tytgat, Guido N. Malfertheiner, Peter Fock, Kivong Ming Heading, Robert C. Katelaris, Peter H. McCarthy, Denis M. McColl, Kenneth El. Moss, Steven F. Sachs, George Sontag, Stephen J. Thomson, Allan B. R. Modlin, Irvin M. TI Whistler Consensus SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Meeting on Gastroesophageal Reflux Disease (GERD) CY SEP, 2006 CL Whistler, CANADA DE acid; PPI; esophagus; reflux ID GASTROESOPHAGEAL-REFLUX DISEASE; HEALTHY MALE-VOLUNTEERS; ACID SUPPRESSION; QUESTIONNAIRE; ESOMEPRAZOLE; METAANALYSIS; PPI AB There is a continuing increase in gastroesophageal reflux disease (GERD), its diverse manifestations and complications worldwide. Indeed the substantial increase in Asia remains is a major epidemiologic and a developing health care issue. This manifesto provides a contemporary review of the current status of areas of uncertainty and in particular highlights the lack of knowledge and unmet needs in the field of GERD biology and especially management. There seems to be no widely accepted rationale for the increasing incidence and prevalence of GERD globally. Although consideration has been given to the decline in Helicobacter pylori infection, others consider the steadily growing problem of obesity as the most likely etiologic factor. What actually comprises the disease entity of GERD continues to confound physicians, and the steady increase in new definitions suggests that a clear picture is still emerging. Of note, however, is the rising awareness of its protean systemic manifestations and the fact that while erosive reflux disease is easily recognizable endoscopically, nonerosive disease (NERD) comprises the majority of presentations in many populations. In view of this, GERD-specific questionnaires and other evaluative tools have been designed to capture the multidimensional nature of the symptom complexes in GERD patients who for the most part may have no endoscopic evidence of disease. Such tools have obvious utility in the evaluation of changes with treatment, especially because there is no endoscopic abnormality detectable. The recognition that NERD is becoming a major clinical entity that requires substantial further investigation is now clearly apparent. At this time, however, little is known of the cellular barrier mechanisms of the esophagus and what is responsible for their reconstitution after injury. Similarly, the neural basis of esophageal pain appreciation, or its relation to the visceral sensory mechanisms that may link NERD with aspects of functional bowel disease are as yet ill understood. Apart from the clinical concern with symptom-focused issues, it is the specter of Barrett esophagus, the most-feared complication of GERD that mostly continues to drive endoscopic practice in GERD. At this time, however, current surveillance strategies remain severely limited in their ability to adequately detect or prevent most esophageal adenocarcinoma. Although considerable effort has been directed at defining the neural circuitry of the esophagus in terms of both motility and sensation, the topography and function of the esophageal-brain-gut axis in respect of the generation of esophageal symptoms remains terra incognita. At this time therefore acid suppression remains the mainstay of therapy in terms of treating the GERD/NERD disease process. Despite the efficacy of the currently available proton pump inhibitor class of drugs, there are clearly unmet needs in this area and agents with a more rapid onset of action and prolonged effect, particularly at night remain important goals in the future advance of pharmacotherapy. C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. McMaster Univ, Hlth Sci Ctr, Hamilton, ON, Canada. Univ Amsterdam, Amsterdam, Netherlands. Otto Von Guericke Univ, Magdeburg, Germany. Changi Gen Hosp, Div Gastroenterol, Singapore, Singapore. Glasgow Royal Infirm, Glasgow, Lanark, Scotland. Univ Sydney, Concord Hosp, Sydney, NSW 2006, Australia. Univ New Mexico, Albuquerque, NM USA. USAF, Vet Affairs Med Ctr, Albuquerque, NM USA. Western Infirm & Associated Hosp, Glasgow, Lanark, Scotland. Rhode Isl Hosp, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. Univ Calif Los Angeles, David Gaffen Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst G, Los Angeles, CA USA. Vet Affairs Hosp, Hines, IL USA. Univ Alberta, Edmonton, AB, Canada. RP Modlin, IM (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. EM imodlin@optonline.net NR 16 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JUL PY 2007 VL 41 IS 6 SU S BP S47 EP S50 DI 10.1097/MCG.0b013e318064c7a3 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188RW UT WOS:000247938000002 ER PT J AU Berquin, IM Min, YN Wu, RP Wu, JS Perry, D Cline, JM Thomas, MJ Thornburg, T Kulik, G Smith, A Edwards, IJ D'Agostino, R Zhang, H Wu, H Kang, JX Chen, YQ AF Berquin, Isabelle M. Min, Younong Wu, Ruping Wu, Jiansheng Perry, Donna Cline, J. Mark Thomas, Mike J. Thornburg, Todd Kulik, George Smith, Adrienne Edwards, Iris J. D'Agostino, Ralph, Jr. Zhang, Hao Wu, Hong Kang, Jing X. Chen, Yong Q. TI Modulation of prostate cancer genetic risk by ornega-3 and ornega-6 fatty acids SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; UNITED-STATES; PHOSPHATIDYLINOSITOL 3-KINASE; PTEN; BAD; CELLS; FISH; EPIGENETICS; EXPRESSION; DOMAIN AB Although a causal role of genetic alterations in human cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Epidemiological studies suggest that diets rich in omega-3 polyunsaturated fatty acids reduce cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. We found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, whereas omega-6 fatty acids had opposite effects. Introducing an omega-3 desaturase, which converts omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3-induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. Our data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study highlights the importance of gene-diet interactions in prostate cancer. C1 Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27109 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. So Yangtze Univ, Sch Food Sci & Technol, Lab Food Biotechnol, Wuxi, Peoples R China. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Boston, MA USA. RP Chen, YQ (reprint author), Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27109 USA. EM yqchen@wfubmc.edu RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NCI NIH HHS [P01 CA106742, R01 CA107668] NR 51 TC 132 Z9 135 U1 1 U2 15 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 JUL PY 2007 VL 117 IS 7 BP 1866 EP 1875 DI 10.1172/JCI31494 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187HG UT WOS:000247837700018 PM 17607361 ER PT J AU Jinushi, M Nakazaki, Y Dougan, M Carrasco, DR Mihm, M Dranoff, G AF Jinushi, Masahisa Nakazaki, Yukoh Dougan, Michael Carrasco, Daniel R. Mihm, Martin Dranoff, Glenn TI MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; DENDRITIC CELLS; DEFICIENT MICE; TGF-BETA; IN-VIVO; EXPRESSION; CANCER; GROWTH; PHAGOCYTOSIS AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances protection against tumors and infections, but GM-CSF-deficient mice develop inflammatory disease. Here we show that GM-CSF is required for the expression of milk fat globule EGF 8 (MFG-E8) in antigen-presenting cells, and that MFG-E8-mediated uptake of apoptotic cells is a key determinant of GM-CSF-triggered tolerance and immunity. Upon exposure to apoptotic cells, GM-CSF-deficient antigen-presenting cells (APCs) produce an altered cytokine profile that results in decreased Tregs and increased Th1 cells, whereas concurrent ablation of IFN-gamma promotes Th17 cells. In wild-type mice, MFG-E8 attenuates the vaccination activity of GM-CSF-secreting tumor cells through Treg induction, whereas a dominant-negative MFG-E8 mutant potentiates GM-CSF-stimulated tumor destruction through Treg inhibition. These findings clarify the immunoregulatory effects of apoptotic cells and suggest new therapeutic strategies to modulate CD4(+) T cell subsets in cancer and autoimmunity. C1 Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu RI Jinushi, Masahisa/A-4311-2012 NR 46 TC 118 Z9 118 U1 1 U2 3 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 JUL PY 2007 VL 117 IS 7 BP 1902 EP 1913 DI 10.1172/JCI30966 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187HG UT WOS:000247837700022 PM 17557120 ER PT J AU Babitt, JL Huang, FW Xia, Y Sidis, Y Andrews, NC Lin, HY AF Babitt, Jodie L. Huang, Franklin W. Xia, Yin Sidis, Yisrael Andrews, Nancy C. Lin, Herbert Y. TI Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REPULSIVE GUIDANCE MOLECULE; ANTIMICROBIAL PEPTIDE HEPCIDIN; JUVENILE HEMOCHROMATOSIS; HEREDITARY HEMOCHROMATOSIS; RENAL FIBROSIS; DIETARY IRON; MOUSE MODEL; EXPRESSION; LIVER; INFLAMMATION AB Systemic iron balance is regulated by, hepcidin, a peptide hormone secreted by the liver. By decreasing cell surface expression of the iron exporter ferroportin, hepcidin decreases iron absorption from the intestine and iron release from reticuloendothelial stores. Hepcidin excess has been implicated in the pathogenesis of anemia of chronic disease, while hepcidin deficiency has a key role in the pathogenesis of the iron overload disorder hemochromatosis. We have recently shown that hemojuvelin is a coreceptor for bone morphogenetic protein (BMP) signaling and that BMP signaling positively regulates hepcidin expression in liver cells in vitro. Here we show that BMP-2 administration increases hepcidin expression and decreases serum iron levels in vivo. We also show that soluble hemojuvelin (HJV.Fc) selectively inhibits BMP induction of hepcidin expression in vitro and that administration of HJV.Fc decreases hepcidin expression, increases ferroportin expression, mobilizes splenic iron stores, and increases serum iron levels in vivo. These data support a role for modulators of the BMP signaling pathway in treating diseases of iron overload and anemia of chronic disease. C1 Massachusetts Gen Hosp, Harvard Med Sch, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. Dana Farber Canc Inst, Harvard Med Sch, Childrens Hosp, Boston, MA 02115 USA. RP Babitt, JL (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. EM jbabitt@partners.org OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [T32 HL007623, T32 HL07623]; NIDDK NIH HHS [R01 DK069533, K08 DK075846, K08 DK075846-01, K08 DK075846-02, R01 DK053813, R01 DK053813-10, R01 DK071837, R01 DK69533, R01 DK71837] NR 52 TC 266 Z9 285 U1 1 U2 13 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 JUL PY 2007 VL 117 IS 7 BP 1933 EP 1939 DI 10.1172/JCI31342 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187HG UT WOS:000247837700025 PM 17607365 ER PT J AU Looft-Wilson, R Murata, T Salomone, S Shin, HK Ayata, C Moskowitz, MA Michel, T Sessa, WC Huang, PL AF Looft-Wilson, Robin Murata, Takahisa Salomone, Salvatore Shin, Hwa Kyoung Ayata, Cenk Moskowitz, Michael A. Michel, Thomas Sessa, William C. Huang, Paul L. TI The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL NO SYNTHASE; PROTEIN-KINASE AKT; L-ARGININE; CELLS; ACTIVATION; MICE; EXPRESSION; PATHWAY; GENE AB NO plays critical roles in vascular function. We show that modulation of the eNOS serine 1179 (S1179) phosphorylation site affects vascular reactivity and determines stroke size in vivo. Transgenic mice expressing only a phosphomimetic (S1179D) form of eNOS show greater vascular reactivity, develop less severe strokes, and have improved cerebral blood flow in a middle cerebral artery occlusion model than mice expressing an unphosphorylatable (S1179A) form. These results provide a molecular mechanism by which multiple diverse cardiovascular risks, such as diabetes and obesity, may be centrally integrated by eNOS phosphorylation in vivo to influence blood flow and cardiovascular disease. They also demonstrate the in vivo relevance of posttranslational modification of eNOS in vascular function. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pharmacol & Mol Med, New Haven, CT USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,Room 4101, Charlestown, MA 02129 USA. EM phuangl@partners.org RI Dantas, Ana Paula/I-4100-2015; OI Dantas, Ana Paula/0000-0001-8514-4094; Salomone, Salvatore/0000-0001-5307-6103 NR 31 TC 0 Z9 0 U1 1 U2 3 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 JUL PY 2007 VL 117 IS 7 BP 1961 EP 1967 DI 10.1172/JCI29877 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187HG UT WOS:000247837700028 ER PT J AU Taylor, NS Xu, S Nambiar, P Dewhirst, FE Fox, JG AF Taylor, Nancy S. Xu, Shilu Nambiar, Prashant Dewhirst, Floyd E. Fox, James G. TI Enterohepatic Helicobacter species are prevalent in mice from commercial and academic institutions in Asia, Europe, and North America SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; HEPATICUS INFECTION; LABORATORY MICE; SCID MICE; MULTIPLEX PCR; INBRED MICE; SP NOV.; BILIS; IDENTIFICATION; RODENTIUM AB The discovery of Helicobacter hepaticus and its role in hepatitis, hepatocellular carcinoma, typhlocolitis, and lower-bowel carcinoma in murine colonies was followed by the isolation and characterization of other Helicobacter spp. involved in enterohepatic disease. Colonization of mouse colonies with members of the family Helicobacteriaceae has become an increasing concern for the research community. From 2001 to 2005, shipments of selected gift mice from other institutions and mice received from specified commercial vendors were screened for Helicobacter spp. by culture of cecal tissue. The identities of the isolates were confirmed by genus-specific PCR, followed by species-specific PCR and restriction fragment length polymorphism analysis. Sequencing of the 16S rRNA gene was performed if the species identity was not apparent. The survey included 79 mice from 34 sources: 2 commercial sources and 16 research sources from the United States and 1 commercial source and 15 research sources from Canada, Europe, or Asia. Helicobacter spp. were cultured from the ceca of 62 of 79 mice. No Helicobacter spp. were found in mice from advertised Helicobacter- free production areas from two U.S. vendors. Multiple Helicobacter spp. were found in mice from one vendor's acknowledged Helicobacter-infected production area. The European commercial vendor had mice infected with novel Helicobacter sp. strain MIT 96-1001. Of the U.S. academic institutions, 6 of 16 (37%) had mice infected with Helicobacter hepaticus; but monoinfection with H. bilis, H. mastomyrinus, H. rodentium, and MIT 96-1001 was also encountered, as were mice infected simultaneously with two Helicobacter spp. Non-U.S. academic institutions had mice that were either monoinfected with H. hepaticus, monoinfected with seven other Helicobacter spp., or infected with a combination of Helicobacter spp. This survey indicates that 30 of 34 (88%) commercial and academic institutions in Canada, Europe, Asia, Australia, and the United States have mouse colonies infected with Helicobacter spp. Mice from 20 of the 34 institutions (59%) were most commonly colonized with H. hepaticus alone or in combination with other Helicobacter spp. These results indicate that a broad range of Helicobacter spp. infect mouse research colonies. The potential impact of these organisms on in vivo experiments continues to be an important issue for mice being used for biomedical research. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCI NIH HHS [R01 CA067529, R01 CA67529]; NIDCR NIH HHS [DE 016937, R37 DE016937, U01 DE016937]; NIEHS NIH HHS [P30-ES02109, P30 ES002109] NR 32 TC 50 Z9 55 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2007 VL 45 IS 7 BP 2166 EP 2172 DI 10.1128/JCM.00137-07 PG 7 WC Microbiology SC Microbiology GA 190QB UT WOS:000248072900012 PM 17507523 ER PT J AU Lin, NU Winer, EP AF Lin, Nancy U. Winer, Eric P. TI Optimal use of aromatase inhibitors: To lead or to follow? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EARLY BREAST-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ADJUVANT TAMOXIFEN; CLINICAL-OUTCOMES; THERAPY; LETROZOLE; ANASTROZOLE; COMBINATION; RECURRENCE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 21 TC 3 Z9 3 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 JUL 1 PY 2007 VL 25 IS 19 BP 2639 EP 2641 DI 10.1200/JCO.2007.10.9447 PG 3 WC Oncology SC Oncology GA 187QB UT WOS:000247862000001 PM 17563391 ER PT J AU Maki, RG Wathen, JK Patel, SR Priebat, DA Okuno, SH Samuels, B Fanucchi, M Harmon, DC Schuetze, SM Reinke, D Thall, PF Benjamin, RS Baker, LH Hensley, ML AF Maki, Robert G. Wathen, J. Kyle Patel, Shreyaskumar R. Priebat, Dennis A. Okuno, Scott H. Samuels, Brian Fanucchi, Michael Harmon, David C. Schuetze, Scott M. Reinke, Denise Thall, Peter F. Benjamin, Robert S. Baker, Laurence H. Hensley, Martee L. TI Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas 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 ADAPTIVE DOSE-RESPONSE; EUROPEAN-ORGANIZATION; SOLID TUMORS; ACUTE STROKE; TRIAL; DOXORUBICIN; IFOSFAMIDE; CANCER; CHEMOTHERAPY; RESISTANT AB Purpose Gemcitabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma. To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel. Patients and Methods In this open-label phase II clinical trial, the primary end point was tumor response, defined as complete or partial response or stable disease lasting at least 24 weeks. A Bayesian adaptive randomization procedure was used to produce an imbalance in the randomization in favor of the superior treatment, accounting for treatment-subgroup interactions. Results One hundred nineteen of 122 randomly assigned patients had assessable outcomes. The adaptive randomization assigned 73 patients (60%) to gemcitabine-docetaxel and 49 patients (40%) to gemcitabine alone, indicating gemcitabine-docetaxel was superior. The objective Response Evaluation Criteria in Solid Tumors response rates were 16% (gemcitabine-docetaxel) and 8% (gemcitabine). Given the data, the posterior probabilities that gemcitabine-docetaxel was superior for progression-free and overall survival were 0.98 and 0.97, respectively. Median progression-free survival was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone; median overall survival was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The posterior probability that patients receiving gemcitabine-docetaxel had a shorter time to discontinuation for toxicity compared with gemcitabine alone was .999. Conclusion Gemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Dept Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Sarcoma Ctr, Dept Med, Houston, TX 77030 USA. Washington Canc Inst, Hematol Oncol Sect, Washington, DC USA. Mayo Clin, Rochester, MN USA. Univ Illinois, Chicago, IL USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. Massachusetts Gen Hosp, Ctr Canc, Partners Hlth CAre, Boston, MA USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Maki, RG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave,Box 223, New York, NY 10021 USA. EM makir@mskcc.org FU NCI NIH HHS [P01-CA47179] NR 44 TC 280 Z9 300 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2007 VL 25 IS 19 BP 2755 EP 2763 DI 10.1200/JCO.2006.10.4117 PG 9 WC Oncology SC Oncology GA 187QB UT WOS:000247862000021 PM 17602081 ER PT J AU Freedman, RA Wirth, LJ Chirieac, LR Huang, EC AF Freedman, Rachel A. Wirth, Lori J. Chirieac, Lucian R. Huang, Eric C. TI Glioblastoma in a patient with early-stage tonsil cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; SQUAMOUS-CELL CARCINOMA; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; DISTANT METASTASES; HEAD; EXPRESSION; EGFRVIII; TUMORS; BRAIN C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 18 TC 3 Z9 3 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 JUL 1 PY 2007 VL 25 IS 19 BP 2848 EP 2850 DI 10.1200/JCO.2007.11.3530 PG 4 WC Oncology SC Oncology GA 187QB UT WOS:000247862000035 PM 17602090 ER PT J AU Kinrys, G Worthington, JJ Wygant, L Nery, F Reese, H Pollack, MH AF Kinrys, Gustavo Worthington, John J. Wygant, Lisa Nery, Fernanda Reese, Hannah Pollack, Mark H. TI Levetiracetam as adjunctive therapy for refractory anxiety disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 24th Congress of the Collegium-Internationale-Neuro-Psychopharmacologicum CY JUN 20-24, 2004 CL Paris, FRANCE SP Collegium Int Neuro Psychopharmacol ID ANTIEPILEPTIC DRUG LEVETIRACETAM; POSTTRAUMATIC-STRESS-DISORDER; BINDING-SITE; OPEN-LABEL; OLANZAPINE; TRIAL AB Background: Anxiety disorders are the most prevalent psychiatric disorders as a group, and despite the effectiveness of currently available treatments for anxiety, many patients remain symptomatic after initial intervention. Thus, there is a significant need for efficacious pharmacologic agents that are safe and well ated and lead patients to remission of symptoms. We present a retrospective analysis that assessed the efficacy and tolerability of adjunctive levetiracetam, a novel anticonvulsant agent, in the treatment of refractory anxiety. Method: Forty patients with DSM-IV anxiety disorders, who were deemed partial responders or nonresponders to anxiolytic therapy, received adjunctive levetiracetam in a naturalistic fashion during the time period from January 2004 December 2004. We conducted a retrospective chart review. The primary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) scale and the Clinical Global Impressions-Improvement (CGI-1) scale. Mean change from baseline to endpoint was assessed using 2-tailed paired t tests. Results: Levetiracetam at a mean +/- SD dose of 1969 +/- 819 mg/day for a mean +/- SD time period of 9.3 +/- 5.1 weeks was generally well tolerated. Patients were markedly ill with a mean SD baseline CGI-S score of 6.2 +/- 0.6. Patients improved significantly, with an endpoint CGI-S score of 4.2 +/- 1.8 (p <.001) and CGI-I score of 2.6 +/- 1.2. Adverse events were generally mild, and only 4 patients discontinued levetiracetam because of side effects. Conclusion: These preliminary data suggest that levetiracetam may be an effective adjunctive treatment for patients with anxiety disorders who remain symptomatic despite initial anxiolytic therapy. C1 Cambridge Hlth Alliance, Anxiety Disorders Res Program, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Kinrys, G (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge Hlth Alliance, 1493 Cambridge St, Cambridge, MA 02139 USA. EM gkinrys@challiance.org NR 22 TC 10 Z9 10 U1 0 U2 1 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 JUL PY 2007 VL 68 IS 7 BP 1010 EP 1013 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 196PK UT WOS:000248494300005 PM 17685735 ER PT J AU Monuteaux, MC Spencer, TJ Faraone, SV Wilson, AM Biederman, J AF Monuteaux, Michael C. Spencer, Thomas J. Faraone, Stephen V. Wilson, Angela M. Biederman, Joseph TI A randomized, placebo-controlled clinical trial of bupropion for the prevention of smoking in children and adolescents with attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT National-Cancer-Institute-Tobocco-Control Investigators Meeting CY JUN 02-04, 2004 CL San Diego, CA SP Natl Canc Inst Tabacco Control Investigators ID DEFICIT HYPERACTIVITY DISORDER; ILLICIT DRUG-USE; CIGARETTE-SMOKING; ADULTS; ADHD; METHYLPHENIDATE; PHARMACOTHERAPY; DESIPRAMINE; INITIATION; MECHANISM AB Objective: Since attention-deficit/hyperactivity disorder (ADHD) is a well-documented risk factor for smoking and bupropion has been shown to be effective for smoking cessation, we tested the efficacy of bupropion as a prophylactic agent for the prevention of smoking in children and adolescents with ADHD. Method: We conducted a longitudinal, randomized, double-blind, placebo-controlled, parallel-group study of bupropion at a large, urban, outpatient medical center. Recruitment began in April 1999, and the last subject was followed until September 2004. Patients were nonsmoking youth, of both sexes, between 9 and 18 years of age, with DSM-IV ADHD. After random assignment to either bupropion or placebo, subjects were assessed weekly for 8 weeks, biweekly for 4 weeks, and monthly thereafter for up to 6.5 years (mean 12 months). Also, patients received treatment with psychostimulants for ADHD symptoms as needed. To assess smoking, we used an assay of cotinine in urine. Results: Fifty-seven subjects (28 receiving bupropion and 29 receiving placebo) were randomly assigned and included in the analysis. No differences were found between the bupropion and placebo groups on demographic factors. About half of each group was treated with stimulants for ADHD. Statistical separation between bupropion and placebo in the rate of smoking initiation or continued smoking was not demonstrated. However, secondary post hoc analyses revealed that concurrent stimulant treatment was significantly associated with a lower rate of smoking onset (hazard ratio [HR] = 0.2, 95% CI = 0.08 to 0.89; z = -2.2, p =.03) and a lower rate of continued smoking (HR = 0.3, 95% CI = 0. 11 to 0.85; z = -2.3, p =.02). Conclusion: While bupropion was not associated with a lower rate of smoking in youth with ADHD, post hoc analyses suggest that stimulant treatment was. Future controlled studies should investigate the role of stimulants in the prevention of smoking in children and adolescents with ADHD. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Monuteaux, MC (reprint author), Pediat Psychopharmacol Program, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM mmonuteaux@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [R01 DA12531-02] NR 38 TC 25 Z9 25 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2007 VL 68 IS 7 BP 1094 EP 1101 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 196PK UT WOS:000248494300018 PM 17685748 ER PT J AU Jensen, RA Gilliam, LK Torn, C Landin-Olsson, M Karlsson, FA Palmer, JP Kockum, I Akesson, K Lernmark, B Lynch, K Breslow, N Lernmark, A AF Jensen, Richard A. Gilliam, Lisa K. Torn, Carina Landin-Olsson, Mona Karlsson, F. Anders Palmer, Jerry P. Kockum, Ingrid Akesson, Karin Lernmark, Barbro Lynch, Kristian Breslow, Norman Lernmark, Ake CA DISS grp TI Multiple factors affect the loss of measurable C-peptide over 6 years in newly diagnosed 15- to 35-year-old diabetic subjects SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE type 1 diabetes mellitus; type 2 diabetes mellitus; c-peptide; autoantibodies ID GLUTAMIC-ACID DECARBOXYLASE; BETA-CELL FUNCTION; MATCHED CONTROL CHILDREN; ISLET-CELL; YOUNG-ADULTS; INSULIN REQUIREMENT; PREDICTIVE VALUE; ANTIBODIES; AUTOANTIBODIES; MELLITUS AB Objective: The aim of this study is to identify risk factors for the loss of measurable plasma C-peptide in newly diagnosed 15- to 35-year-old diabetic subjects. Methods: This Swedish study included 778 subjects. C-peptide levels were obtained each year for 6 years after diagnosis. Loss of measurable C-peptide was defined as a level at or below the lower detection limit of the local assay (0.13 nmol/1). In addition to C-peptide, other baseline covariates included gender, age, body mass index, HLA genotype, and autoantibody levels. Results: Compared with autoantibody-negative subjects, autoantibody-positive subjects had lower median baseline C-peptide (0.27 vs. 0.50, P<.001), their levels declined over the study period, and the risk of losing measurable C-peptide was significantly higher when more than one autoantibody was present [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.13-7.54]. Among autoantibody-positive individuals, the presence of GAD65Ab (OR, 1.8; 95% CI, 1.24-2.51) and islet cell antibodies (OR, 1.6; 95% CI, 1.19-2.18) conferred a higher risk for loss of measurable C-peptide.as did female gender (OR, 1.6; 95% CI, 1.17-2.11) and time after diagnosis (OR, 1.5 for each additional year postdiagnosis; 95% CI, 1.41-1.57). Higher baseline C-peptide levels were protective (OR, 0.5 for each additional log, nanomoles per liter; 95% CI, 0.36-0.58). Conclusions: This study identified autoantibody status, gender, and baseline C-peptide levels as factors that will be useful for predicting the disease course of 15- to 35-year-old diabetic individuals. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Med, RH Williams Lab, Med Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Lund Hosp, Dept Clin Sci, S-22185 Lund, Sweden. Univ Uppsala Hosp, Inst Med Sci, Uppsala, Sweden. Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Karolinska Inst, Dept Mol Med, Stockholm, Sweden. Ryhovs Hosp, Dept Phys, Jonkoping, Sweden. Lund Univ, Dept Clin Sci, Univ Hosp MAS, Malmo, Sweden. RP Jensen, RA (reprint author), Univ Washington, Dept Med, RH Williams Lab, Med Ctr, 1959 NE Pacific St,Box 357710, Seattle, WA 98195 USA. EM richaj@u.washington.edu OI Landin-Olsson, Mona/0000-0003-0510-9112 FU NIDDK NIH HHS [DK42654, DK26910, DK17047, DK53004] NR 40 TC 16 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL-AUG PY 2007 VL 21 IS 4 BP 205 EP 213 DI 10.1016/j.jdiacomp.2006.01.004 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 191XU UT WOS:000248166100001 PM 17616349 ER PT J AU Gilliam, FR Singh, JP Mullin, CM McGuire, M Chase, KJ AF Gilliam, F. Roosevelt, III Singh, Jagmeet P. Mullin, Christopher M. McGuire, Maureen Chase, Kellie J. TI Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE heart failure; heart rate; mortality; cardiac resynchronization therapy ID FAILURE; TRIAL; CARDIOMYOPATHY; DEVICE AB Background: Cardiac resynchronization therapy devices provide effective therapy for heart failure. Heart rate variability (HRV) parameters in the device such as HRV footprint and SD of average 5-minute intrinsic R-R intervals (SDANN) are related to autonomic function and may be used to identify patients with a higher risk of mortality. Methods: We examined the relationship between HRV and mortality in a prospective cohort study. The 842 patients (mean age, 67.7 +/- 11.2; 23.5 % female; New York Heart Association class III, 88.6%; class IV, 11.4%) included in the analysis were implanted with a cardiac resynchronization therapy with defibrillation device and had baseline HRV measurements available. Results: During a median of 11.6 months of follow-up, 7.8% (66/842) of patients died. Heart rate variability footprint and SDANN were significant predictors of mortality (all P <.05); patients with lower HRV values were at greater risk for death, compared with patients with higher HRV values. Heart rate variability changes over time tended to predict the risk of mortality in follow-up (P nonsignificant), ; patients with low baseline HRV and small changes in HRV during the follow-up period were at the highest risk for death (7% mortality for SDANN and 8.9% for HRV footprint), and patients with high baseline HRV and large changes in HRV were at the lowest risk (1.5% mortality for SDANN and 2.4% for HRV footprint). Results were consistent when adjusted for age, sex, body mass index, and diastolic blood pressure. Conclusions: Continuously measured device HRV parameters provide prognostic information about patient mortality that may be helpful for risk stratification. (c) 2007 Elsevier Inc. All rights reserved. C1 NE Arkansas, Jonesboro, AR 72401 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Integra Grp, Brooklyn Pk, MN USA. Boston Sci CRM, St Paul, MN USA. RP Gilliam, FR (reprint author), NE Arkansas, Jonesboro, AR 72401 USA. EM rgilliam@arkheart.com NR 20 TC 12 Z9 13 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD JUL-AUG PY 2007 VL 40 IS 4 BP 336 EP 342 DI 10.1016/j.jelectrocard.2006.11.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 189XP UT WOS:000248022200004 PM 17320897 ER PT J AU Lamm, R Nadel, ES Brown, DFM AF Lamm, Ruth Nadel, Eric S. Brown, David F. M. TI Abdominal pain and ascites SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID OVARIAN HYPERSTIMULATION SYNDROME; HUMAN ALBUMIN; IVF C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2007 VL 33 IS 1 BP 65 EP 70 DI 10.1016/j.jemermed.2007.03.050 PG 6 WC Emergency Medicine SC Emergency Medicine GA 194CR UT WOS:000248322100013 PM 17630078 ER PT J AU Seim, AR Dahl, DM Sandberg, WS AF Seim, Andreas R. Dahl, Douglas M. Sandberg, Warren S. TI Small changes in operative time can yield discrete increases in operating room throughput SO JOURNAL OF ENDOUROLOGY LA English DT Article ID ANESTHESIA; DECREASES; INDUCTION; SURGEONS AB Background and Purpose: Operating room throughput is influenced by the efficiency of the perioperative process ( for nonoperative time) and by the surgeon ( for operative time). Operative time is thought not to be easily amenable to deliberate reductions. We tested the hypothesis that gradual improvements in operative time had allowed one surgeon to perform additional cases during scheduled hours. Materials and Methods: The surgeon had been working in both a high-throughput and a conventional operating room for more than 1 year prior to the study. During the studied interval, we applied statistical process control analysis to time data for the surgeon performing full days of complex laparoscopic operations. Separate analyses were conducted for the conventional and high-throughput operating rooms. The average operative time for each day and the number of cases per day were plotted against sequential days for each environment. Results: Midway through the studied interval, there was a discrete 17-minute drop in operative time in both the high-throughput and the conventional environment. Throughput increased from two cases per day to three per day in the high-throughput environment. The average end time for the three-case days was 17: 15 ( range 16: 04-18: 32). Longer average operative and nonoperative times in the conventional rooms precluded performing three complex cases during regular work hours. Conclusion: There was a sudden, rather than a gradual, reduction of operative time leading to extra cases being performed. This coincided with ( 1) the surgeon being assigned a new fellow and ( 2) administrative commitment to finish three cases per day. Our original hypothesis was negated, but other controllable causes for changes in surgical throughput were identified. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. Norwegian Univ Sci & Technol, Dept Prod & Qual Engn, N-7034 Trondheim, Norway. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM wsandberg@PARTNERS.ORG NR 18 TC 11 Z9 11 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD JUL PY 2007 VL 21 IS 7 BP 703 EP 708 DI 10.1089/end.2007.0030 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 202FN UT WOS:000248887500008 PM 17705754 ER PT J AU Walsh, TJ Porter, MP AF Walsh, Thomas J. Porter, Michael P. TI Ureteroscopic treatment of upper-tract urothelial lesions: A novel technique SO JOURNAL OF ENDOUROLOGY LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; MANAGEMENT; BIOPSY AB We describe a simple and effective method of using a stone-extraction basket and electrocautery to treat pedunculated renal-pelvic neoplasms ureteroscopically. This technique may make it easier to obtain tissue from the urothelium and reduce operative times. C1 Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Va Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Walsh, TJ (reprint author), Univ Washington, Sch Med, Dept Urol, 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA. EM TWalsh@urology.ucsf.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD JUL PY 2007 VL 21 IS 7 BP 718 EP 720 DI 10.1089/end.2006.0344 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 202FN UT WOS:000248887500011 PM 17705757 ER PT J AU Lynch, CS Chang, JC Ford, AF Ibrahim, SA AF Lynch, Cheryl Sterling Chang, Judy C. Ford, Angela F. Ibrahim, Said A. TI Obese African-American women's perspectives on weight loss and bariatric surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE African American; obesity; body mass index; weight loss; bariatric surgery ID IN-HOSPITAL OUTCOMES; LONG-TERM MORTALITY; HEALTH-CARE USE; UNITED-STATES; LOSS MAINTENANCE; NATIONAL TRENDS; MORBID-OBESITY; US ADULTS; PREVALENCE; ATTITUDES AB Background: African-American (AA) women have higher rates of obesity and obesity-related diseases but are less likely than other women to undergo bariatric surgery or have success with conventional weight loss methods. Objective: To explore obese AA women's perceptions regarding barriers to weight loss and bariatric surgery. Design: Focus groups to stimulate interactive dialogue about beliefs and attitudes concerning weight management. Participants and approach: We partnered with a community organization to recruit women who were AA, were >= 18 years old, and had a body mass index (BMI) of >= 30 kg/m(2). We audiotaped the 90-minute focus groups and used content analysis for generating and coding recurring themes. Results: In our sample of 41 participants, the mean age was 48.8 years and mean BMI was 36.3. Most participants were unmarried, had some postsecondary education, and reported good or fair health. About 85% knew someone who had undergone bariatric surgery. Qualitative analysis of 6 focus group sessions revealed that the most common barriers to weight loss were lack of time and access to resources; issues regarding self-control and extrinsic control; and identification with a larger body size. Common barriers to bariatric surgery were fears and concerns about treatment effects and perceptions that surgery was too extreme or was a method of last resort. Conclusions: Only through the elimination of barriers can AA women receive the care needed to eliminate excess weight and prevent obesity-related morbidity and mortality. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Minor Hlth, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151-C, Pittsburgh, PA 15240 USA. EM said.ibrahim2@med.va.gov FU NCATS NIH HHS [UL1 TR000005]; NIMHD NIH HHS [P60 MD-000-207-03] NR 50 TC 28 Z9 28 U1 4 U2 8 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 JUL PY 2007 VL 22 IS 7 BP 908 EP 914 DI 10.1007/s11606-007-0218-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 183DH UT WOS:000247552400002 PM 17447097 ER PT J AU Bai, JH Dittman, JS Kaplan, JM AF Bai, Jihong Dittman, Jeremy S. Kaplan, Joshua M. TI Quantifying synaptic vesicle protein dynamics. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 27 BP 12a EP 12a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600029 ER PT J AU Lizunov, VA Kirchhausen, T Zimmerberg, J AF Lizunov, Vladimir A. Kirchhausen, Tom Zimmerberg, Joshua TI Reversible fluctuations of the endocytotic fission pore induced by dynamin inhibitor dynasore. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 NIH, NICHHD, Lab Mol Cellular & Mol Phys, Bethesda, MD 20892 USA. Harvard Med Sch, Ctr Blood Res Inst Biomed Res, Dept Cell Biol, Boston, MA 02115 USA. RI Lizunov, Vladimir/B-5468-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 40 BP 17a EP 17a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600042 ER PT J AU Saffarian, S Kirchhausen, T AF Saffarian, Saveez Kirchhausen, Tom TI Formation of clathrin-coated pits monitored in living cells by fluorescence microscopy with 10-nm axial resolution. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 Harvard Med Sch, Ctr Blood Res Inst Biomed Res, Dept Cell Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 41 BP 17a EP 18a PG 2 WC Physiology SC Physiology GA 182RB UT WOS:000247520600043 ER PT J AU Mallette, P Zhao, MJ Zurakowski, D Ring, D AF Mallette, Paige Zhao, Meijuan Zurakowski, David Ring, David TI Muscle atrophy at diagnosis of carpal and cubital tunnel syndrome SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE atrophy; carpal tunnel syndrome; cubital tunnel syndrome ID INTERNAL NEUROLYSIS; MEDIAN NERVE; SURGERY; HAND AB Purpose: This study was designed to test the hypothesis that patients with an initial diagnosis of cubital tunnel syndrome are more likely to present with muscle atrophy than patients with an initial diagnosis of carpal tunnel syndrome. Methods: A list of patients presenting to the office of a single hand surgeon from January 2000 to June 2005 with an initial diagnosis of isolated, idiopathic carpal tunnel syndrome or cubital tunnel syndrome was generated from billing records. The medical records of 58 patients with cubital tunnel syndrome and 370 patients with carpal tunnel syndrome were reviewed for age, gender, diabetes, and presence of atrophy. Results: Twenty-three of 58 patients with an initial diagnosis of cubital tunnel syndrome had atrophy compared with only 62 out 370 patients with an initial diagnosis of carpal tunnel syndrome. Multiple logistic regression revealed that age (odds ratio, 1.06; 95% CI, 1.04-1.08) and diagnosis (cubital tunnel patients were more likely than carpal tunnel patients to present with atrophy; odds ratio, 4.5; 95% CI, 2.7-8.6) were factors significantly associated with atrophy at presentation. Conclusions: Patients with carpal tunnel syndrome present earlier in the course of their disease than patients with cubital tunnel syndrome. Patients with cubital tunnel syndrome are more likely to present with muscle atrophy, reflecting advanced nerve damage that may not respond to surgery. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 12 TC 14 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL-AUG PY 2007 VL 32A IS 6 BP 855 EP 858 DI 10.1016/j.jhsa.2007.03.009 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 192IP UT WOS:000248195000014 PM 17606066 ER PT J AU Barrett, TW Mori, M De Boer, D AF Barrett, Thomas W. Mori, Motomi De Boer, David TI Association of ambulatory use of statins and beta-blockers with long-term mortality after vascular surgery SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE vascular surgery; beta-blockers; statins; mortality ID MAJOR NONCARDIAC SURGERY; PERIOPERATIVE MYOCARDIAL-ISCHEMIA; PROPENSITY SCORE METHODS; AORTIC-ANEURYSM SURGERY; OF-VETERANS-AFFAIRS; HIGH-RISK PATIENTS; LOWER-EXTREMITY; REDUCTION; INFARCTION; MORBIDITY AB BACKGROUND: The use of drugs to improve postoperative outcomes has focused oil short-term end points and centered on beta-blockers. Emerging evidence suggests statins may also improve postoperative Outcomes. OBJECTIVE: We sought to ascertain if the ambulatory use of statins and/or beta-blockers was associated with a reduction in long-term mortality after vascular surgery. DESIGN: Retrospective cohort study with a median follow-tip of 2 7 years. SETTING: Regional multicenter study at Veterans Affairs medical centers. PATIENTS: Three thousand and sixty-two patients presenting for vascular surgery. MEASUREMENTS: Patients were categorized as using statins or beta-blockers if they filled a prescription for the study drug within 30 days of surgery. Survival analyses, propensity score methods, and stratifications by the revised cardiac risk index (RCRI) were performed. RESULTS: Propensity-adjusted ambulatory use of statins and beta-blockers was associated with a reduction in mortality over the study period compared with nonuse of these medications hazard ratio [HR] = 0.78 [95% CI: 0.67-0.921, P = .0021, and number needed to treat (NNT) = 22 for statins; HR = 0.84 [95% CI: 0.73-0.961, P = .0106, and NNT = 30 for beta-blockers. In addition, for propensity-adjusted use of both statins and beta-blockers compared with neither the HR was 0.56 [95% CI: 0.42-0.74] P < .0001, and NNT was 9. The RCRI confirmed combination statin and beta-blocker use was beneficial at all levels of risk. Use of the combination Study drugs by the highest-risk patients was associated with a 33% decrease in mortality after 2 years (P = .0106). CONCLUSIONS: The use of ambulatory statins alone or in combination with beta-blockers is associated with a reduction in long-term mortality after vascular surgery, and combination use benefits patients at all levels of risk. C1 [Barrett, Thomas W.] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Barrett, Thomas W.] Portland VA Med Ctr, Sect Gen Med, Portland, OR USA. [Mori, Motomi] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA. [De Boer, David] Oregon Hlth & Sci Univ, Ctr Biostat Comp & Informat Biol & Med, Portland, OR 97201 USA. RP Barrett, TW (reprint author), 3710 SW US VA Hosp Rd,Portland P3MED, Portland, OR 97207 USA. EM barretth@ohsu.edu NR 33 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JUL-AUG PY 2007 VL 2 IS 4 BP 241 EP 252 DI 10.1002/jhm.160 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 292HQ UT WOS:000255257500007 PM 17702038 ER PT J AU Greve, B Weissert, R Hamdi, N Bettelli, E Sobel, RA Coyle, A Kuchroo, VK Rajewsky, K Schmidt-Supprian, M AF Greve, Bernhard Weissert, Robert Hamdi, Nada Bettelli, Estelle Sobel, Raymond A. Coyle, Anthony Kuchroo, Vijay K. Rajewsky, Klaus Schmidt-Supprian, Marc TI I kappa B kinase 2/beta deficiency controls expansion of autoreactive T cells and suppresses experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MICE; ACTIVATION; PATHWAY; INHIBITION; PEPTIDE; SYSTEM; TARGET; DIFFERENTIATION AB The NF-kappa B family of transcription factors plays a pivotal role in T cell activation and survival during (auto) immune responses. I kappa B kinase 2/beta (IKK2) is part of the I kappa B kinase complex, a central component of the intracellular signaling pathway mediating NF-kappa B activation. We studied the role of IKK2 in autoantigen-specific T cell activation and induction of autoimmune disease using mice that lack this kinase specifically in T cells (IKK2 Delta Tcell mice). We found highly impaired myelin-oligodendrocyte-glycoprotein (MOG)(35-55)-specific T cell activation in vitro and complete resistance to MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE) in IKK2(Delta T cell) C57BL/6 mice in vivo. By contrast, transgenic expression of a pathogenic MOG(35-55)-specific TCR (2D2 TCR) rendered IKK2(Delta T cell) mice susceptible to MOG(35-55)-induced EAE and restored in vitro MOG(35-55)-specific T cell responses, indicating an expansion defect in IKK2-deficient T cells. Treatment with the IKK2-inhibitory compound PS-1145 reduced MOG(35-55)-specific proliferation and cytokine production of 2D2 transgenic spleen cells in vitro and diminished clinical signs of EAE in vivo. Our data underscore the potential of therapeutic IKK inhibition in autoimmune diseases. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Hertie Inst Clin Brain Res, Tubingen, Germany. Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Vet Affairs Hlth Care Syst, Palo Alto, CA 94304 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. RP Schmidt-Supprian, M (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM supprian@cbr.med.harvard.edu RI Weissert, Robert/B-2585-2009; Schmidt-Supprian, Marc/F-5893-2011 OI Weissert, Robert/0000-0002-1295-1271; Schmidt-Supprian, Marc/0000-0002-8543-6166 FU NIAID NIH HHS [AI 057947] NR 28 TC 20 Z9 21 U1 1 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 JUL 1 PY 2007 VL 179 IS 1 BP 179 EP 185 PG 7 WC Immunology SC Immunology GA 182IF UT WOS:000247497600025 PM 17579036 ER PT J AU Moran, ST Cariappa, A Liu, H Muir, B Sgroi, D Boboila, C Pillai, S AF Moran, Stewart T. Cariappa, Annaiah Liu, Haoyuan Muir, Beth Sgroi, Dennis Boboila, Cristian Pillai, Shiv TI Synergism between NF-kappa B1/p50 and Notch2 during the development of marginal zone B lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR-KAPPA-B; CELL DEVELOPMENT; POSITIVE SELECTION; SIGNALING PATHWAY; T-CELLS; MICE; BAFF; EXPRESSION; ACTIVATION; RESPONSES AB NF-kappa B1 and Notch2 are both required for the development of marginal zone (MZ) B cells. Analysis of B lymphocyte development in mice that are doubly heterozygous at the Notch2 and NF-kappa B1 loci revealed synergism between Notch2 and NF-kappa B1 during MZ B cell development. Two known transcriptional targets of the Notch pathway, Hes-5 and Deltex-1, were found to be preferentially expressed in MZ B cells and regulated by NF-kappa B1. These studies provide in vivo evidence for a genetic interaction between the Notch and NF-kappa B pathways. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NCI NIH HHS [CA 102973]; NIAID NIH HHS [AI 064930] NR 40 TC 44 Z9 45 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 JUL 1 PY 2007 VL 179 IS 1 BP 195 EP 200 PG 6 WC Immunology SC Immunology GA 182IF UT WOS:000247497600027 PM 17579038 ER PT J AU Ahluwalia, N Lin, AY Tager, AM Pruitt, IE Anderson, TJT Kristo, F Shen, DX Cruz, AR Aikawa, M Luster, AD Gerszten, RE AF Ahluwalia, Neil Lin, Alexander Y. Tager, Andrew M. Pruitt, Ivy E. Anderson, Thomas J. T. Kristo, Fjoralba Shen, Dongxiao Cruz, Anna R. Aikawa, Masanori Luster, Andrew D. Gerszten, Robert E. TI Inhibited aortic aneurysm formation in BLT1-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID E-DEFICIENT MICE; LEUKOTRIENE B-4 RECEPTORS; POLYMORPHONUCLEAR LEUKOCYTES; ATHEROSCLEROTIC LESIONS; 5-LIPOXYGENASE PATHWAY; MYOCARDIAL-INFARCTION; PLAQUE INSTABILITY; GENETIC DEFICIENCY; CELL RECRUITMENT; ARACHIDONIC-ACID AB Leukotriene B-4 is a proinflammatory lipid mediator generated by the enzymes 5-lipoxygenase and leukotriene A, hydrolase. Leukotriene B-4 signals primarily through its high-affinity G protein-coupled receptor, BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. In this study, we tested the hypothesis that BLT1 is necessary for abdominal aortic aneurysm (AAA) formation, a major complication of atherosclerotic vascular disease. Chow-fed Apoe(-1-) and Apoe(-/-)/Blt1(-/-) mice were treated with a 4-wk infusion of angiotensin II (1000 ng/min/kg) beginning at 20 wk of age, in a well-established murine AAA model. We found a reduced incidence of AAA formation as well as concordant reductions in the maximum suprarenal/infrarenal diameter and total suprarenal/infrarenal area in the angiotensin II-treated Apoe(-/-)/Blt1(-/-) mice as compared with the Apoe(-/-) controls. Diminished AAA formation in BLT1-deficient mice was associated with significant reductions in mononuclear cell chemoattractants and leukocyte accumulation in the vessel wall, as well as striking reductions in the production of matrix metalloproteinases-2 and -9. Thus, we have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice and that BLT1 deletion in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity. These findings extend the role of BLT1 to a critical complication of vascular disease and underscore its potential as a target for intervention in modulating multiple pathologies related to atherosclerosis. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Div Cardiovasc, Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA 02115 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, E 8307,149 13th St, Charlestown, MA 02129 USA. EM rgerszten@partners.org NR 34 TC 51 Z9 54 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 JUL 1 PY 2007 VL 179 IS 1 BP 691 EP 697 PG 7 WC Immunology SC Immunology GA 182IF UT WOS:000247497600081 PM 17579092 ER PT J AU Lahey, TP Loisel, SD Wieland-Alter, W AF Lahey, Timothy P. Loisel, Suzanne D. Wieland-Alter, Wendy TI Glucocorticoid-induced tumor necrosis factor receptor family-related protein triggering enhances HIV-specific CD4(+) T cell cytokine secretion and protects HIV-specific CD4(+) T cells from apoptosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PERIPHERAL-BLOOD; INFECTED INDIVIDUALS; GASTROINTESTINAL-TRACT; CD8-T-CELL MEMORY; IMMUNE-RESPONSES; CD4-T-CELL HELP; UP-REGULATION; TNF RECEPTOR; CD40 LIGAND AB Human immunodeficiency virus ( HIV)-specific CD4(+) T cell cytokine secretion is characteristically weak during HIV infection, in part because HIV-specific CD4(+) T cells undergo massive apoptotic deletion. Glucocorticoid-induced tumor necrosis factor ( TNF) receptor family-related ( GITR) protein triggering enhances murine antigen-specific T cell cytokine secretion by protecting T cells from apoptosis. Therefore, we investigated the impact of GITR triggering on HIV-specific CD4(+) T cell cytokine secretion and on apoptosis of HIV-specific CD4(+) T cells. In HIV-infected subjects, CD4(+) T cell surface expression of GITR was greater than that in uninfected control subjects, and phytohemagglutinin induction of additional GITR expression was impaired. However, antibody triggering of GITR significantly increased HIV-specific CD4(+) T cell expression of TNF-alpha and interferon ( IFN)-gamma. The percentage increase in HIV-specific CD4(+) T cell expression of TNF-alpha correlated directly with the absolute peripheral CD4(+) T cell count. Furthermore, GITR triggering reduced the expression of intracellular activated caspase-3 in HIV-specific CD4(+) T cells. Taken together, these data suggest that, despite abnormal GITR expression during HIV infection, GITR triggering enhances HIV-specific CD4(+) T cell cytokine expression and protects HIV-specific CD4(+) T cells from apoptosis. C1 Dartmouth Coll Sch Med, Sect Infect Dis & Int Hlth, Lebanon, NH 03756 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lahey, TP (reprint author), Dartmouth Coll Sch Med, Sect Infect Dis & Int Hlth, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Timothy.Lahey@Dartmouth.edu FU NHLBI NIH HHS [K30 HL004095]; NIAID NIH HHS [1 K08 AI069915-01, K08 AI069915-01, K08 AI069915] NR 48 TC 13 Z9 14 U1 0 U2 0 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 JUL 1 PY 2007 VL 196 IS 1 BP 43 EP 49 DI 10.1086/518613 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175BL UT WOS:000246987100009 PM 17538882 ER PT J AU Gelfand, EV Cannon, CP AF Gelfand, E. V. Cannon, C. P. TI Myocardial infarction: contemporary management strategies SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE myocardial infarction; primary percutaneous coronary intervention; thrombolysis ID ACUTE CORONARY SYNDROMES; ST-SEGMENT-ELEVATION; PLATELET GLYCOPROTEIN IIB/IIIA; LEFT-VENTRICULAR DYSFUNCTION; RANDOMIZED CONTROLLED-TRIAL; ENZYME-INHIBITOR TRANDOLAPRIL; PLACEBO-CONTROLLED TRIAL; EARLY INVASIVE STRATEGY; HIGH-RISK PATIENTS; UNSTABLE ANGINA AB Myocardial infarction (MI) is a common clinical diagnosis, associated with significant morbidity and mortality, not only in the short term, but also years following the index event. A more complete understanding of the pathophysiology of MI has ushered the era of multipronged treatment approach, with a combination of goal-directed revascularization, a broad adjunctive pharmacological therapy and aggressive secondary prevention measures. The goals of this article are to review the basic pathophysiological processes, which lead up to a clinical diagnosis of MI, to highlight the essential elements of clinical presentation and to summarize the evidence for comprehensive therapy. Emphasis has been placed on the choice of primary reperfusion therapy for ST-elevation MI, on risk-stratification of patients with non-ST elevation MI, and on rationale behind the selection of anti-ischaemic and antithrombotic therapy. Finally, evidence-based approach to secondary prevention is outlined. C1 Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol,TIMI Study Grp, Boston, MA 02115 USA. RP Gelfand, EV (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, E-RW-453,300 Brookline Ave, Boston, MA 02215 USA. EM egelfand@bidmc.harvard.edu NR 106 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUL PY 2007 VL 262 IS 1 BP 59 EP 77 DI 10.1111/j.1365-2796.2007.01790.x PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 183OB UT WOS:000247581000005 PM 17598815 ER PT J AU Jansen, PL Rosch, R Jansen, M Binnebosel, M Junge, K Alfonso-Jaume, A Klinge, U Lovett, DH Mertens, PR AF Jansen, Petra Lynen Rosch, Raphael Jansen, Marc Binneboesel, Marcel Junge, Karsten Alfonso-Jaume, Alexandra Klinge, Uwe Lovett, David H. Mertens, Peter R. TI Regulation of MAV-2 gene transcription in dermal wounds SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GLOMERULAR MESANGIAL CELLS; A-DEFICIENT MICE; MATRIX METALLOPROTEINASE-2; IV COLLAGENASE; TUMOR PROGRESSION; EXPRESSION; YB-1; ANGIOGENESIS; INHIBITION; INFLAMMATION AB Matrix metalloproteinase-2 (MMP-2, gelatinase A) plays an essential role in angiogenesis, inflammation, and fibrosis. These processes are critical for wound healing and accordingly elevated levels of MMP-2 expression have been detected after skin injury. Our goal was to investigate the transcriptional activation of the MMP-2 gene in a model of skin injury by using two different MM P-2/LacZ-reporter mice. Upon skin injury MMP-2 expression was upregulated, whereas tissue from normal skin stained negative except for occasional macrophages, sweat glands, and hair follicles. Skin injury also activated MMP-2 proteolytic activity and reporter gene expression. We demonstrate that MMP-2 regulatory sequences -1686/+423 drive appropriate injury-induced MMP-2-promoter activation. Reporter gene expression was predominantly detectable in endothelial cells and in macrophages. Deletion of the 5' responsive element, denoted RE-1, residing at -1241/+423 bp of the regulatory sequence led to abrogated MMP-2 transcription in vivo. The findings define a crucial role for the enhancer element RE-1 in injury-induced MMP-2 transcription of the skin. C1 Univ Hosp Aachen, Interdisciplinary Ctr Clin Res BIOMAT, RWTH Aachen, D-52074 Aachen, Germany. Univ Hosp, RWTH Aachen, Dept Surg, Aachen, Germany. Williams Middleton Mem Univ Wisconsin, Dept Med, Madison, WI USA. Univ Hosp RWTH Aachen, Inst Appl Med Engn, Helmholtz Inst, Aachen, Germany. Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Hosp Aachen, RWTH Aachen, Dept Nephrol, Aachen, Germany. Univ Hosp Aachen, RWTH Aachen, Dept Clin Immunol, Aachen, Germany. RP Jansen, PL (reprint author), Univ Hosp Aachen, Interdisciplinary Ctr Clin Res BIOMAT, RWTH Aachen, Pauwelsstr, D-52074 Aachen, Germany. EM plynen@ukaachen.de FU NIDDK NIH HHS [DK039776] NR 25 TC 23 Z9 23 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 JUL PY 2007 VL 127 IS 7 BP 1762 EP 1767 DI 10.1038/sj.jid.5700765 PG 6 WC Dermatology SC Dermatology GA 184YB UT WOS:000247677400034 PM 17344928 ER PT J AU Pan, QL Mathison, J Fearns, C Kravchenko, VV Correia, JD Hoffman, HM Kobayashi, KS Bertin, J Grant, EP Coyle, AJ Sutterwala, FS Ogura, Y Flavell, RA Ulevitch, RJ AF Pan, Qilin Mathison, John Fearns, Colleen Kravchenko, Vladimir V. Correia, Jean Da Silva Hoffman, Hal M. Kobayashi, Koichi S. Bertin, John Grant, Ethan P. Coyle, Anthony J. Sutterwala, Fayyaz S. Ogura, Yasunori Flavell, Richard A. Ulevitch, Richard J. TI MDP-induced interleukin-1 beta processing requires Nod2 and CIAS1/NALP3 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokine; inflammation; PAMP; NLR ID TOLL-LIKE RECEPTORS; BACTERIAL MURAMYL DIPEPTIDE; CROHNS-DISEASE; INNATE IMMUNITY; METABOLIC-INHIBITORS; ADAPTIVE IMMUNITY; INFLAMMASOME; CASPASE-1; ACTIVATION; MACROPHAGES AB Nucleotide-binding oligomerization domain (Nod)2 is a sensor of muramyl dipeptides (AIDP) derived from bacterial peptidoglycan. Nod2 also plays a role in some autoinflammatory diseases. Cold-induced autoinflammatory syndrome I (CIAS1)/NACHT domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NALP3) has been suggested to be sufficient for MDP-dependent release of mature IL-1 beta, but the role of Nod2 in this process is unclear. Using mice bearing selective gene deletions, we provide in vitro and in vivo data showing that AIDP-induced IL-1 beta release requires Nod2 and CIASI/NALP3 as well as receptor-interacting protein-2 (Rip2), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1. In contrast, AIDP-dependent IL-6 production only requires Nod2 and Rip2. Together, our data provide a new understanding of this important pathway of IL-I beta production and allow for further studies of the role of these proteins within the broader context of inflammatory disease. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Ludwig Inst Canc Res, La Jolla, CA USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT USA. RP Ulevitch, RJ (reprint author), Scripps Res Inst, Dept Immunol, IMM12,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ulevitch@scripps.edu NR 39 TC 86 Z9 87 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2007 VL 82 IS 1 BP 177 EP 183 DI 10.1189/jlb.1006627 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 186FR UT WOS:000247765000018 PM 17403772 ER PT J AU Ogino, S Kawasaki, T Kirkner, GJ Kraft, P Loda, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Kirkner, Gregory J. Kraft, Peter Loda, Massimo Fuchs, Charles S. TI Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID DNA METHYLATION; MICROSATELLITE INSTABILITY; BRAF MUTATION; COLON-CANCER; KRAS; EPIGENETICS; PROFILES; PATTERNS; SURVIVAL; TUMORS AB The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation is a distinct phenotype in colorectal cancer. However, a choice of markers for CIMP has been controversial. A recent extensive investigation has selected five methylation markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) as surrogate markers for epigenomic aberrations in tumor. The use of these markers as a CIMP-specific panel needs to be validated by an independent, large dataset. Using MethyLight assays on 920 colorectal cancers from two large prospective cohort studies, we quantified DNA methylation in eight CIMP-specific markers [the above five plus CDKN2A (p16), CRABP1, and MLH1]. A CIMP-high cutoff was set at >= 6/8 or >= 5/8 methylated promoters, based on tumor distribution and BRAF/KRAS mutation frequencies. All but two very specific markers [MLH1 (98% specific) and SOCS1 (93% specific)] demonstrated >= 85% sensitivity and >= 80% specificity, indicating overall good concordance in methylation patterns and good performance of these markers. Based on sensitivity, specificity, and false positives and negatives, the eight markers were ranked in order as: RUNX3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1, and CDKN2A. In conclusion, a panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP-high. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA055075, P01 CA087969, P01 CA55075, P01 CA87969] NR 35 TC 186 Z9 193 U1 0 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2007 VL 9 IS 3 BP 305 EP 314 DI 10.2353/jmoldx.2007.060170 PG 10 WC Pathology SC Pathology GA 185DJ UT WOS:000247691200005 PM 17591929 ER PT J AU Finberg, KE Sequist, LV Joshi, VA Muzikansky, A Miller, JM Han, M Beheshti, J Chirieac, LR Mark, EJ Iafrate, AJ AF Finberg, Karin E. Sequist, Lecia V. Joshi, Victoria A. Muzikansky, Alona Miller, Julie M. Han, Moonjoo Beheshti, Javad Chirieac, Lucian R. Mark, Eugene J. Iafrate, A. John TI Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID GROWTH-FACTOR-RECEPTOR; GENE COPY NUMBER; CANCER PATIENTS; GEFITINIB SENSITIVITY; ACTIVATING MUTATIONS; ERLOTINIB; CARCINOMA; SURVIVAL; SMOKING; PREDICTORS AB Somatic mutations in the epidermal growth factor receptor gene (EGFR) are detected in a subset of lung adenocarcinomas, particularly bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (AWBF), and correlate with clinical response to tyrosine kinase inhibitors (TKIs). in contrast, lung adenocarcinomas refractory to TKIs often have activating mutations in KRAS but lack EGFR mutations. Some adenocarcinomas have mucinous histology, but the clinical and molecular significance of the mucinous pattern is less well studied. We analyzed 43 BAC and AWBF tumors submitted for EGFR mutation testing to identify histopathological features that predicted EGFR or KRAS mutations. EGFR mutations were detected in 14 of 30 (47%) non-mucinous tumors, whereas 0 of 13 mucinous tumors harbored an EGFR mutation (P = 0.003). Missense mutations in KRAS codon 12 were detected in six of seven (86%) mucinous adenocarcinomas but only 3 of 18 (17%) nonmucinous adenocarcinomas (P = 0.003). Thus, in BAC/AWBF mucinous differentiation was significantly correlated with the absence of EGFR mutation and presence of KRAS mutation, suggesting that mucinous BACs/AWBFs are unlikely to respond to TKIs. Therefore, our data suggest that EGFR sequence analysis could be avoided in BAC/AWBF when true mucinous morphology is identified, avoiding the associated testing costs. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Mol Med Lab, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM aiafrate@partners.org NR 37 TC 113 Z9 117 U1 1 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2007 VL 9 IS 3 BP 320 EP 326 DI 10.2353/jmoldx.2007.060182 PG 7 WC Pathology SC Pathology GA 185DJ UT WOS:000247691200007 PM 17591931 ER PT J AU Mollica, RF Caridad, KR Massagli, MP AF Mollica, Richard F. Caridad, Kathleen Rey Massagli, Michael P. TI Longitudinal study of posttraumatic stress disorder, depression, and changes in traumatic memories over time in Bosnian refugees SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE posttraumatic stress disorder; traumatic memories; event reporting; depression ID MENTAL-HEALTH; VETERANS; EXPOSURE; EVENTS; COMORBIDITY; DISABILITY; PTSD; WAR; CONSISTENCY; SYMPTOMS AB This longitudinal study examined traumatic memory consistency over a 3-year period among a sample of highly traumatized Bosnian refugees, focusing on demographic factors, types of trauma, and posttraumatic stress disorder (PTSD) and depression. In 1996 and 1999, 376 Bosnian refugees were inter-viewed about 54 wartime trauma and torture events, and symptoms of PTSD and depression. Reports were compared for both time periods, and changed responses were analyzed for significance. Overall, there was consistency in reporting over time; when change occurred it was in the direction of decreased reports at follow-up. This downward trend was not associated with any particular diagnosis. However, PTSD alone, without comorbid symptoms of depression, was uniquely associated with the group that exhibited an upward trend. This implies that increased reporting is related specifically to the presence of PTSD symptoms, and that PTSD may be distinctly associated with the failed extinction of traumatic memories. C1 Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mollica, RF (reprint author), Harvard Univ, Program Refugee Trauma, 22 Putnam Ave, Cambridge, MA 02139 USA. EM rmollica@partners.org FU NIMH NIH HHS [MH 57806-02] NR 34 TC 43 Z9 43 U1 1 U2 2 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 JUL PY 2007 VL 195 IS 7 BP 572 EP 579 DI 10.1097/NMD.0b013e318093ed2c PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 191WS UT WOS:000248163300004 PM 17632247 ER PT J AU Harpold, T Biederman, J Gignac, M Hammerness, P Surman, C Potter, A Mick, E AF Harpold, Theresa Biederman, Joseph Gignac, Martin Hammerness, Paul Surman, Craig Potter, Anya Mick, Eric TI Is oppositional defiant disorder a meaningful diagnosis in adults? Results from a large sample of adults with ADHD SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE oppositional defiant disorder; adults; ADHD ID DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY; CHILDHOOD AB We examined the prevalence and clinical characteristics of oppositional defiant disorder (ODD) in a sample of clinically referred adults with attention deficit hyperactivity disorder (ADHD). Subjects were consecutively referred adults with a DSM-III R/IV diagnosis of ADHD with or without ODD. Nearly half of subjects (43%) had a history of ODD. Subjects with a childhood history of ODD had increased risk for bipolar disorder, multiple anxiety disorders, and substance use disorders relative to the ADHD subjects without ODD. We concluded, as in children with ODD, adults with a childhood history of ODD have high rates of psychiatric comorbidity and more impaired psychosocial functioning than those without this condition. A better understanding of the course, phenomenology, and clinical significance of ODD in adults is needed to better understand therapeutic approaches for this disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Univ Montreal, Inst Philippe Pinel, Montreal, PQ H3C 3J7, Canada. RP Mick, E (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM mick@helix.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [K01 MH065523] NR 16 TC 25 Z9 27 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2007 VL 195 IS 7 BP 601 EP 605 DI 10.1097/NMD.0b013e318093f448 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 191WS UT WOS:000248163300008 PM 17632251 ER PT J AU Kim, JH Kim, D Park, SH Lee, HB Chung, EK AF Kim, Jin Hun Kim, Daeho Park, Sung-Hyouk Lee, Hwang Bin Chung, Eun Kee TI Novelty-seeking among schizophrenia patients with comorbid alcohol abuse SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE alcohol; schizophrenia; temperament ID SELF-MEDICATION HYPOTHESIS; SUBSTANCE-ABUSE; PERSONALITY; DISORDERS; TEMPERAMENT; ASSOCIATION; HISTORY; RISK AB Since characterological characteristics of patients with schizophrenia and comorbid alcohol abuse are not well established, we compared outpatients with DSM-IV schizophrenia, with (n = 5 1) and without alcohol-abuse (n = 51), matched for sex, age, IQ, and symptom severity, using the Temperament and Character Inventory. Dual-diagnosis patients showed highly selective greater novelty seeking. C1 Seoul Natl Univ Hosp, Dept Psychiat, Schizophrenia Res Grp, Seoul 143711, South Korea. Hanyang Univ, Coll Med, Dept Neuropsychiat, Guri, South Korea. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Psychot Disorders Program, Boston, MA 02114 USA. RP Kim, JH (reprint author), Seoul Natl Univ Hosp, Dept Psychiat, Schizophrenia Res Grp, 51 Neungdong Ro, Seoul 143711, South Korea. EM kimjinhun@schizophrenia-research.com NR 22 TC 12 Z9 12 U1 2 U2 6 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 JUL PY 2007 VL 195 IS 7 BP 622 EP 624 DI 10.1097/NMD.0b013e318093f425 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 191WS UT WOS:000248163300012 PM 17632255 ER PT J AU Khan, M Elango, C Ansari, MA Singh, I Singh, AK AF Khan, Mushfiquddin Elango, Chinnasamy Ansari, Mubeen A. Singh, Inderjit Singh, Avtar K. TI Caffeic acid phenethyl ester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE antioxidant; caffeic acid phenethyl ester; inflammation; neurovascular protection; oxidative stress; therapeutic window ID NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; ARTERY OCCLUSION; GENE-EXPRESSION; EXPERIMENTAL STROKE; S-NITROSYLATION; ENDOTHELIAL-CELLS; VASCULAR-DISEASE; OXIDATIVE STRESS; INJURY AB Ischemic stroke is a neurovascular disease treatable by thrombolytic therapy, but the therapy has to be initiated within 3 h of the incident. This therapeutic limitation stems from the secondary injury which results mainly from oxidative stress and inflammation. A potent antioxidant/anti-inflammatory agent, caffeic acid phenethyl ester (CAPE) has potential to mitigate stroke's secondary injury, and thereby widening the therapeutic window. We observed that CAPE protected the brain in a dose-dependent manner (1-10 mg/kg body weight) and showed a wide therapeutic window (about 18 h) in a rat model of transient focal cerebral ischemia and reperfusion. The treatment also increased nitric oxide and glutathione levels, decreased lipid peroxidation and nitrotyrosine levels, and enhanced cerebral blood flow. CAPE down-regulated inflammation by blocking nuclear factor kappa B activity. The affected mediators included adhesion molecules (intercellular adhesion molecule-1 and E-selectin), cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and inducible nitric oxide synthase. Anti-inflammatory action of CAPE was further documented through reduction of ED1 (marker of activated macrophage/microglia) expression. The treatment inhibited apoptotic cell death by down-regulating caspase 3 and up-regulating anti-apoptotic protein Bcl-xL. Conclusively, CAPE is a promising drug candidate for ischemic stroke treatment due to its inhibition of oxidative stress and inflammation, and its clinically relevant wide therapeutic window. C1 Med Univ S Carolina, Dept Pathol & Lab Med, Children Res Inst 516, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Children Res Inst 516, 173 Ashley Ave, Charleston, SC 29425 USA. EM khanm@musc.edu FU Intramural NIH HHS; NINDS NIH HHS [NS-37766, NS-22576, NS-34741, NS-40144, NS-40810] NR 66 TC 59 Z9 68 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2007 VL 102 IS 2 BP 365 EP 377 DI 10.1111/j.1471-4159.2007.04526.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 183OE UT WOS:000247581300008 PM 17437550 ER PT J AU Gray, F Polivka, M Viswanathan, A Baudrimont, M Bousser, MG Chabriat, H AF Gray, Francoise Polivka, Marc Viswanathan, Anand Baudrimont, Marie Bousser, Marie-Germaine Chabriat, Hugues TI Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE apoptosis; CADASIL; cortical atrophy; Lacunar infarct; status cribrosus (etat crible); subcortical white matter; white matter damage ID ISCHEMIC VASCULAR-DISEASE; NEURONAL APOPTOSIS; ADULT-RAT; SERIAL SECTIONS; CORTICAL-NEURONS; SENSORY NEURONS; BRAIN INFARCTS; AXONAL INJURY; WHITE-MATTER; CADASIL AB To test the hypothesis that an apoptotic process plays a role in the pathogenesis of cerebral lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we examined samples from frontal, temporal, insular, and occipital regions, basal ganglia, and cerebellum from 4 patients with CADASIL, 2 with Binswanger disease, and 3 controls. Apoptotic cells were identified using in situ end labeling and activated caspase 3 immunostaining. Immunolabeling for Notch3, the P-amyloid protein precursor, and phosphorylated neurofilament protein was performed on successive sections. Apoptosis of vascular cells was markedly increased in status cribrosus in CADASIL, both in basal ganglia and subcortical white matter, suggesting that concomitantly with Notch3 deposition it may play a causative role in the dilatation of Virchow-Robin spaces. Neuronal apoptosis was found in CADASIL, mostly in cortical layers 3 and 5. Its severity correlated serniquantitatively with the extent of ischemic lesions and axonal damage in the underlying white matter. It was more severe in demented patients. Only occasional apoptotic neurons were found in the Binswanger cases and none in the controls. This supports the view that neuronal apoptosis may contribute to cortical atrophy and cognitive impairment in patients with CADASIL and that it may, at least partly, result from axonal damage in the underlying white matter. C1 Univ Paris 07, Hop Lariboisiere, AP HP, Dept Pathol, Paris, France. Univ Paris 07, Hop Lariboisiere, AP HP, Dept Neurol, Paris, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Med Sch, Boston, MA USA. RP Gray, F (reprint author), Hop Lariboisiere, Serv Cent Anat & Cytol Pathol, 2 Rue Ambroise Pare, F-75475 Paris 10, France. EM francoise.gray@lrb.ap-hop-paris.fr RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 52 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 2007 VL 66 IS 7 BP 597 EP 607 DI 10.1097/nen.0b013e318093e574 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 189YQ UT WOS:000248025200004 PM 17620985 ER PT J AU Portera-Cailliau, C Russ, C Brown, RH Budson, AE Vonsattel, JP Folkerth, RD Corbo, JC AF Portera-Cailliau, Carlos Russ, Carsten Brown, Robert H., Jr. Budson, Andrew E. Vonsattel, Jean-Paul Folkerth, Rebecca D. Corbo, Joseph C. TI A familial form of pallidoluysionigral degeneration and amyotrophic lateral sclerosis with divergent clinical presentations SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ALS-FTD; frontotemporal dementia; motor neuron disease; parkinsonism; primary progressive aphasia; Tau; ubiquitin ID MOTOR-NEURON DISEASE; FRONTAL-LOBE DEMENTIA; FRONTOTEMPORAL DEMENTIA; PROGRESSIVE APHASIA; NIGRAL ATROPHY; COMPLEX; PARKINSONISM; LOCUS; ALS; NEUROPATHOLOGY AB We describe a family with a rapidly progressive neurodegenerative disorder characterized by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) but with unusual neuropathologic features that include pallidoluysionigral degeneration. The proband presented with primary progressive aphasia that evolved into mutism. He subsequently developed dementia with mild disinhibition and parkinsonism and late in the disease showed evidence of motor neuron disease. Two other cases (the proband's mother and maternal uncle) had features of ALS exclusively. All 3 had a young onset (fourth decade) and rapid clinical course, with average time from onset of symptoms to death of 4 years. Postmortem neuropathologic examination of the proband and his uncle showed ALS changes and extensive pallidoluysionigral degeneration without neurofibrillary tangles, ubiquitin inclusions, or detectable abnormalities in the dentate nucleus of the cerebellum. Although this exceptional combination of neuropathologic features has been described in rare cases of sporadic ALS-FTD, no pedigrees have ever been reported. In 2 affected members of this family, we failed to identify mutations in genes associated with weakness, movement disorders, or dementia, including ALS, FTD, selected spinocerebellar ataxias, and Huntington disease. Thus, this disorder may represent a novel autosomal dominantly inherited and rapidly progressive neurodegenerative disorder with a spectrum of clinical presentations but common neuropathologic features. C1 Univ Calif Los Angeles, Dept Neurol, Reed Neurol Res Ctr, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Neuromusc Res, Charlestown, MA USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Columbia Univ, Med Ctr, Dept Pathol, New York, NY USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Portera-Cailliau, C (reprint author), Univ Calif Los Angeles, Dept Neurol, Reed Neurol Res Ctr, A-145,710 Westwood Pl, Los Angeles, CA 90095 USA. EM cpcailliau@mednet.ucla.edu OI Corbo, Joseph/0000-0002-9323-7140 NR 50 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 2007 VL 66 IS 7 BP 650 EP 659 DI 10.1097/nen.0b013e318093f40d PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 189YQ UT WOS:000248025200009 PM 17620990 ER PT J AU Panizzon, K Mousavi, O Wallis, RA AF Panizzon, Kimberly Mousavi, Omid Wallis, Roi Ann TI Treatment with simvastatin protects against the increased susceptibility to trauma of CA1 hippocampal neurons in aged animals SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 25th Annual National-Neurotrauma-Society Symposium CY JUL 29-AUG 01, 2007 CL Kansas City, MO SP Natl Neurotrauma Soc C1 VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2007 VL 24 IS 7 MA P96 BP 1253 EP 1253 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 186DV UT WOS:000247760200106 ER PT J AU Pellegrino, D Cicchetti, F Wang, XK Zhu, AJ Yu, MX Saint-Pierre, M Brownell, AL AF Pellegrino, Daniela Cicchetti, Francesca Wang, Xukui Zhu, Aijun Yu, Mexiang Saint-Pierre, Martine Brownell, Anna-Liisa TI Modulation of dopaminergic and glutamatergic brain function: PET studies on Parkinsonian rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE neurology; PET; dopamine receptors; dopamine transporter; glutamate receptors; Parkinson's disease ID BASAL GANGLIA; SUBTHALAMIC NUCLEUS; MESSENGER-RNA; IN-VIVO; RECEPTOR; DISEASE; MGLUR5; NEUROTOXICITY; TRANSPLANTS; TERMINALS AB Degeneration of dopaminergic neurons of the substantia nigra pars compacta is a cardinal feature of Parkinson's disease (PD). Although uncertain, the pathology has been suggested to derive from a malfunction of the complex interaction between dopaminergic and metabotropic glutamate receptors (mGluRs). To further address this issue, we investigated the imaging profile and expression of dopamine D-2 receptors and mGluRs in a classic parkinsonian rodent model induced by the toxin 6-hydroxydopamine. Methods: Adult male Sprague-Dawley rats (250-300 g) received a stereotaxic injection of 8 mu g/2 mu L of 6-hydroxydopamine (n = 6) or saline solution (n = 4) in the right medial forebrain bundle. Small-animal PET was performed on all rats 4 wk after the surgical procedure to assess dopamine transporter (DAT) status using C-11-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)-tropane (CFT), as well as dopamine D-2 receptor and mGluR(5) modulation using C-11-raclopride and 2-C-11-methyl-6-(2-phenylethynyl)-pyridine (C-11-M PEP), respectively. Behavioral studies were also conducted 6 wk after lesioning by D-amphetamine challenge. Immunohistochemistry and Western blotting were carried out at 8 wk after lesioning to confirm dopamine fiber, neuronal loss, and level of striatal mGluR(5) expression. Results: PET images showed decreased C-11-CFT binding on the lesioned side, including the structures of the striatum, hippocampus, and cortex, compared with the contralateral intact side. Interestingly, dopamine D-2 receptors and mGluR(5) upregulation were observed in the right striatum, hippocampus, and cortex, using C-11-raclopride and C-11-MPEP, respectively. A negative correlation was also found between the percentage change in mGluR(5) expression and DAT function. Finally, tyrosine hydroxylase immunoreactivity confirmed both dopamine fiber loss (t test, P < 0.01) and neuronal loss (t test, P < 0.01) on the lesioned side. These changes were accompanied by a strongly enhanced mGluR(5) expression in the right striatum of the lesioned side analyzed by Western plot. Conclusion: These findings support the existence of compensatory mechanisms in nigrostriatal dopamine degeneration and provide new insights that help further dissect some of the pathways underlying neurodegeneration. In addition, these results reconfirm that PET is a valuable tool for multilevel receptor studies, significantly contributing to the understanding of pathogenic mechanisms and ultimately opening new avenues in the study of neuroprotective approaches toward PD. C1 Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp,Expt PET Lab, Boston, MA 02114 USA. Univ Laval, Dept Med, Quebec City, PQ G1K 7P4, Canada. RP Brownell, AL (reprint author), Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp,Expt PET Lab, Bartlett Hall,504R, Boston, MA 02114 USA. EM abrownell@partners.org FU NIBIB NIH HHS [EB-001850] NR 36 TC 39 Z9 42 U1 0 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 2007 VL 48 IS 7 BP 1147 EP 1153 DI 10.2967/jnumed.106.037796 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187KK UT WOS:000247846300031 PM 17574972 ER PT J AU Nissenbaum, M Kaban, LB Troulis, MJ AF Nissenbaum, Mark Kaban, Leonard B. Troulis, Maria J. TI Toothache, paresthesia, and horner syndrome: An unusual presentation of disseminated burkitt's lymphoma SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DIAGNOSIS C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM Lkaban@partners.org NR 13 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2007 VL 65 IS 7 BP 1395 EP 1401 DI 10.1016/j.jams.2005.08. PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 185YD UT WOS:000247745400026 PM 17577512 ER PT J AU Zhang, D Johnson, LJ Hsu, HP Spector, M AF Zhang, Dong Johnson, Lanny J. Hsu, Hu-Ping Spector, Myron TI Cartilaginous deposits in subchondral bone in regions of exposed bone in osteoarthritis of the human knee: Histomorphometric study of PRG4 distribution in osteoarthritic cartilage SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE lubricin; PRG4; superficial zone protein; articular cartilage; osteoarthritis ID SUPERFICIAL ZONE PROTEIN; SMOOTH-MUSCLE ACTIN; HUMAN ARTICULAR CHONDROCYTES; SYNOVIAL-FLUID; EXPRESSION; ARTHRITIS; PROTEOGLYCAN-4; LUBRICIN; INJURY; REPAIR AB The objective of this study was to identify and characterize cartilaginous deposits aggregates in the subchondral bone in areas of the human osteoarthritic knee with exposed bone. A specific aim was to determine the distribution of the joint lubrication molecule, lubricin/superficial zone protein [referred to by its gene, proteoglycan4 (PRG4)], in these cartilaginous deposits and in osteoarthritic cartilage. This work was carried out in the context of assessing the potential contribution of these chondrocyte aggregates for joint resurfacing in certain cartilage repair procedures. The discarded bone cuts of femoral condyles and tibial plateaus were collected from 11 patients with advanced osteoarthritis (OA) of the knee during total knee arthroplasty; 9 women and 2 men with a mean age of 68 years. Sections of paraffin-embedded tissue were stained with Safranin-O, and with antibodies to type II collagen, alpha-smooth muscle actin (SMA), and PRG4. Chondrocyte aggregates were found in the subchondral bone of regions of exposed bone in sections from five individuals. The average diameter of cartilaginous aggregates was 152 mu m, and the average depth of the aggregates below the surface was about 475 mu m. Most aggregates were fibrocartilaginous and stained positive for type II collagen. Of interest was the finding that the cartilaginous deposits and osteoarthritic cartilage contained PRG4. Only a small percentage of chondrocytes stained positive for SMA. Cartilaginous deposits containing chondrocyte aggregates exist in subchondral bone in regions of exposed bone in some patients with advanced OA of the knee. These cells may be able to contribute to the resurfacing of the joint in certain cartilage repair procedures (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Orthopaed Res Lab, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu NR 31 TC 30 Z9 31 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUL PY 2007 VL 25 IS 7 BP 873 EP 883 DI 10.1002/jor.20344 PG 11 WC Orthopedics SC Orthopedics GA 179AS UT WOS:000247262300005 PM 17343281 ER PT J AU Laneader, A Angelos, P Ferrell, BR Kolker, A Miner, T Padilla, G Swaney, J Krouse, RS Casarett, D AF Laneader, Alice Angelos, Peter Ferrell, Betty R. Kolker, Ann Miner, Thomas Padilla, Geraldine Swaney, Julie Krouse, Robert S. Casarett, David TI Ethical issues in research to improve the management of malignant bowel obstruction: Challenges and recommendations SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article; Proceedings Paper CT International Conference on Malignant Bowel Obstruction CY NOV 12-13, 2004 CL Pasadena, CA DE end of life; ethics; research ethics; palliative care ID PALLIATIVE CARE RESEARCH; CLINICAL RESEARCH; INFORMED CONSENT; DECISION-MAKING; ADVANCED CANCER; GUIDELINES; DELIRIUM AB Research to improve the care of patients with malignant bowel obstruction (MBO) is urgently needed. In particular, there is an urgent need for high-quality descriptive research, including prospective cohort studies, as well as randomized controlled trials to define optimal management strategies. However, investigators and clinicians face numerous barriers in conducting high-quality research in this patient population. These barriers include lack of funding, difficulties in identifying eligible patients, and a variety of practical and methodological challenges of designing these studies. In addition, there are a variety of ethical challenges that arise in the design and conduct of studies of MBO and particularly in the conduct of clinical trials. In this article, we address four categories of ethical issues: study design, recruitment, informed consent, and Institutional Review Board review. For each, we outline salient issues and suggest recommendations for enhancing the ethics of MBO studies, including interventional trials. C1 Univ Penn, Res Compliance & Qual Improvement, Philadelphia, PA 19104 USA. Univ Chicago, MacLean Ctr Clin Med Eth, Med Ctr, Chicago, IL 60637 USA. City Hope Natl Med Ctr, Dept Nursing Res & Educ, Duarte, CA 91010 USA. Ovarian Canc Natl Alliance, Washington, DC USA. Brown Univ, Sch Med, Dept Surg, Providence, RI 02912 USA. Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. Univ Arizona, Coll Med, Dept Surg, Tucson, AZ 85721 USA. Arizona Vet Affairs Hlth Care, Tucson, AZ USA. Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Univ Penn, Res Compliance & Qual Improvement, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM Casarett@mail.med.upenn.edu NR 33 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2007 VL 34 IS 1 SU S BP S20 EP S27 DI 10.1016/j.jpainsymman.2007.04.007 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 190JN UT WOS:000248055200003 PM 17532176 ER PT J AU Mularski, RA Rosenfeld, K Coons, SJ Dueck, A Cella, D Feuer, DJ Lipscomb, J Karpeh, MS Mosich, T Sloan, JA Krouse, RS AF Mularski, Richard A. Rosenfeld, Kenneth Coons, Stephen Joel Dueck, Amylou Cella, David Feuer, David J. Lipscomb, Joseph Karpeh, Martin S., Jr. Mosich, Tom Sloan, Jeff A. Krouse, Robert S. TI Measuring outcomes in randomized prospective trials in palliative care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article; Proceedings Paper CT International Conference on Malignant Bowel Obstruction CY NOV 12-13, 2004 CL Pasadena, CA DE death; quality of dying; outcome assessment; quality of health care; quality indicators; health care; end-of-life care; family; proxy; terminal care; attitude to death ID OF-LIFE CARE; MALIGNANT BOWEL OBSTRUCTION; HEALTH SURVEY SF-36; FAMILY-MEMBERS; DECISION-MAKING; QUALITY; END; CANCER; DEATH; VALIDATION AB Palliative care aims to improve the quality of life of patients and their families and reduce suffering from life-threatening illness. In assessing palliative care efficacy, researchers must consider a broad range of potential outcomes, including those experienced by the patient's family/caregivers, clinicians, and the health care system. The purpose of this article is to summarize the discussions and recommendations of an Outcomes Working Group convened to advance the palliative care research agenda, particularly in the context of randomized controlled trials. These recommendations address the conceptualization of palliative care outcomes, sources of outcomes data, application of outcome measures in clinical trials, and the methodological challenges to outcome measurement in palliative care populations. As other fields have developed and refined methodological approaches that address their particular research needs, palliative care researchers must do the same to answer important clinical questions in rigorous and credible ways. C1 Oregon Hlth & Sci Univ, Ctr Hlth Res, Kaiser Permanent NW, Portland, OR 97227 USA. NW Permanente PC Kaiser Sunnsyde Med Ctr, Portland, OR USA. Vet Adm Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Arizona, Coll Pharm, Behav Measurement Shared Serv, Tucson, AZ 85721 USA. Univ Arizona, Coll Publ Hlth, Behav Measurement Shared Serv, Tucson, AZ 85721 USA. Arizona Canc Ctr, Tucson, AZ 85721 USA. Mayo Clin, Rochester, MN USA. Evanston NW Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. Barts & London Natl Hlth Serv Trust, St Bartholomews Hosp, Barts & London Palliat Care Team, London, England. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. SUNY Stony Brook, Univ Hosp, Div Surg Oncol, Stony Brook, NY 11794 USA. So Arizona Vet Affairs Hlth Care Syst, Amer Canc Soc, Tucson, AZ USA. Univ Arizona, Coll Med, Tucson, AZ 85721 USA. RP Mularski, RA (reprint author), Oregon Hlth & Sci Univ, Ctr Hlth Res, Kaiser Permanent NW, 3800 N Interstate,WIN 1060, Portland, OR 97227 USA. EM Richard.Mularski@kpchr.org NR 71 TC 22 Z9 23 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2007 VL 34 IS 1 SU S BP S7 EP S19 DI 10.1016/j.jpainsymman.2007.04.004 PG 13 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 190JN UT WOS:000248055200002 PM 17532180 ER PT J AU Bechard, LJ Guinan, EC Feldman, HA Tang, V Duggan, C AF Bechard, Lori J. Guinan, Eva C. Feldman, Henry A. Tang, Vivian Duggan, Christopher TI Prognostic factors in the resumption of oral dietary intake after allogeneic hematopoietic stem cell transplantation (HSCT) in children SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; VERSUS-HOST-DISEASE; THERAPY; RECIPIENTS; MUCOSITIS; SUPPORT; GRAFT; COMPLICATIONS AB Background: Parenteral nutrition (PN) is a common supportive care therapy in patients undergoing hematopoietic stem cell transplantation (HSCT). Inadequate oral dietary intake may necessitate prolonged courses of PN, which have been associated with metabolic, infectious, and hepatobiliary complications. The objective of this study was to identify demographic, clinical, and nutrition factors associated with the resumption of oral dietary intake following HSCT. Methods: This was an observational cohort study of 37 children undergoing allogeneic HSCT. Repeated-measures regression analysis was performed to identify factors associated with the resumption and macronutrient composition of oral nutrient intake after HSCT. Results: Mean oral dietary intake during the first 2 weeks after HSCT was < 280 kcal/d. At all times, oral carbohydrate intake was high, ranging from 58% to 74% of oral energy. Age, time since transplant, degree of oral mucositis, and severity of graft-vs-host disease (GVHD) were all significantly correlated with the resumption of oral energy intake, as well as oral intake of carbohydrates. Oral protein and fat intake were also associated with elapsed time since HSCT, severity of mucositis, and GVHD. Factors not associated with oral dietary intake included gender, pre-HSCT nutrition status, diagnosis, type of donor, and infections. Conclusions: Children undergoing HSCT exhibit a marked reduction in oral dietary intake and a preference for a diet high in carbohydrates. Careful attention should be directed to the oral dietary intake and nutrient requirements of children during HSCT, especially in younger patients and those who experience severe mucositis or GVHD. C1 Childrens Hosp, Clin Nutr Serv, Div GI Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duggan, C (reprint author), Childrens Hosp, Clin Nutr Serv, Div GI Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.duggan@childrens.harvard.edu FU NICHD NIH HHS [K24 HD058795]; NIDDK NIH HHS [P30 DK040561-12, P30 DK040561] NR 31 TC 6 Z9 9 U1 1 U2 1 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JUL-AUG PY 2007 VL 31 IS 4 BP 295 EP 301 DI 10.1177/0148607107031004295 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 195XI UT WOS:000248445300008 PM 17595438 ER PT J AU Spencer, TJ Biederman, J Mick, E AF Spencer, Thomas J. Biederman, Joseph Mick, Eric TI Attention-Deficit/Hyperactivity disorder: Diagnosis, lifespan, comorbidities, and neurobiology SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE attention-deficit/hyperactivity disorder; comorbidity; diagnosis; neurobiology ID DEFICIT-HYPERACTIVITY DISORDER; ABNORMAL-PSYCHICAL-CONDITIONS; OPPOSITIONAL DEFIANT DISORDER; CLINICALLY REFERRED SAMPLE; 15-YEAR FOLLOW-UP; PSYCHIATRIC STATUS; NEUROPSYCHIATRIC SEQUELAE; GOULSTONIAN-LECTURES; MATERNAL SMOKING; CONDUCT DISORDER AB In this report, we provide an evidence-based overview of attention-deficit/hyperactivity disorder (ADHD), including diagnosis, prevalence, developmental expression of symptoms, persistence, the heterogeneity of functional outcome, impairment in afflicted adults, psychiatric comorbidity, pathophysiology, genetics, psychosocial and biologic risk factors, and neurobiology. Attention-deficit/hyperactivity disorder is an early-onset, highly prevalent neurobehavioral disorder, with genetic, environmental, and biologic etiologies, that persists into adolescence and adulthood in a sizable majority of afflicted children of both sexes. It is characterized by behavioral symptoms of inattention, hyperactivity, and impulsivity across the life cycle and is associated with considerable morbidity and disability. Comorbidity is a distinct clinical feature of both childhood and adult ADHD. Although its etiology remains unclear, emerging evidence documents its strong neurobiologic and genetic underpinnings. Despite the high diagnostic reliability and the robust evidence of the validity of ADHD, there are many underlying issues that remain to be resolved. These include establishing developmentally appropriate diagnostic criteria at older ages, further elaborating the impact of gender on symptom expression, and examining risk and protective factors in relationship to prevention or amelioration of ADHD as well as related functional impairments. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Yawkey Ctr Outpatient Care, 32 Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 90 TC 216 Z9 219 U1 3 U2 57 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JUL PY 2007 VL 32 IS 6 BP 631 EP 642 DI 10.1093/jpepsy/jsm005 PG 12 WC Psychology, Developmental SC Psychology GA 190UL UT WOS:000248086000002 PM 17556405 ER PT J AU Beaudry, P Hida, Y Udagawa, T Alwayn, IP Greene, AK Arsenault, D Folkman, J Heymach, JV Ryeom, S Puder, M AF Beaudry, Pau Hida, Yasuhiro Udagawa, Taturo Alwayn, Ian P. Greene, Arin K. Arsenault, Daniette Folkman, Judah Heymach, John V. Ryeom, Sandra Puder, Mark TI Endothetial progenitor cells contribute to accelerated liver regeneration SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE hepatectomy; endothelial progenitor cells; stem cell markers ID CIRCULATING ENDOTHELIAL-CELLS; MARROW-DERIVED STEM; BONE-MARROW; PARTIAL-HEPATECTOMY; SURROGATE MARKER; ANGIOGENESIS; GROWTH; MOBILIZATION; DIFFERENTIATION; IMPLANTATION AB Two classes of circulating endothelial cells (CECs) have been identified and are distinguished by the expression of the stem cell markers CD117 or CD133 together with endothelial-specific antigens.Stem cell marker-positive CECs originate from bone marrow and have been designated as circulating endothelial progenitors (CEPs). We have demonstrated that exogenous vascular endothelial growth. note factor (VEGF) effectively mobilizes CEP cells. Furthermore, it has been demonstrated that VEGF regulates liver regeneration after partial hepatectomy. Although local endothelial cells can regulate tissue mass during liver regeneration, the contribution of CEPs to this process is unknown. We discovered loss of CD117 and CD133 from murine CEP cells and that both markers underestimated the number of bone marrow-derived CEP cells. We therefore used wild type and green fluorescent protein (GFP)-bone marrow transplanted into wild-type mice and performed 70% hepatectomies. Furthermore, we found that treatment with exogenous VEGF accelerated liver regeneration after 70% hepatectomy, whereas immunohistochemical analysis showed a 7-fold increase in the incorporation of CEP cells into liver vasculature. These results suggest that CEP cells play a role in regulating liver regeneration and that VEGF treatment can mobilize CEP cells to accelerate this process. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Puder, M (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. EM mark.puder@childrens.harvard.edu RI Hida, Yasuhiro/A-7761-2012 OI Hida, Yasuhiro/0000-0003-1759-4215 FU NCI NIH HHS [P01 CA45548, P20 CA090578]; NIDDK NIH HHS [DK069621-01] NR 27 TC 34 Z9 37 U1 2 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2007 VL 42 IS 7 BP 1190 EP 1198 DI 10.1016/j.jpedsurg.2007.02.034 PG 9 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 199JT UT WOS:000248692800006 PM 17618879 ER PT J AU Kingsberg, S Shifren, J Wekselman, K Rodenberg, C Koochaki, P DeRogatis, L AF Kingsberg, Sheryl Shifren, Jan Wekselman, Kathryn Rodenberg, Cynthia Koochaki, Patricia DeRogatis, Leonard TI Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE benefit; hypoactive sexual desire disorder; postmenopausal women; transdermal testosterone ID SURGICALLY MENOPAUSAL WOMEN; PLACEBO; PATCH; DYSFUNCTION; PREVALENCE; HEALTH; PROFILE; TRIALS AB Introduction. Postmenopausal women with hypoactive sexual desire disorder (HSDD) experienced statistically significant improvements in the frequency of satisfying sexual activity, sexual desire, and distress with testosterone treatment in phase III trials, but it was not known whether the magnitude of these effects was clinically meaningful. The clinical relevance study was designed to answer this question. Aim. To evaluate the clinical relevance of the treatment benefits. Methods. This study involved a representative sample of 132 surgically postmenopausal women with HSDD who were enrolled in two randomized, placebo-controlled trials (N = 1094) assessing the efficacy and safety of transdermal testosterone treatment (300 mcg/day) for 6 months. At the end of the studies, prior to unblinding, a sample of women (12%) was interviewed concerning their experiences with the treatment. Main Outcome Measures. Women were asked "Overall, would you say that you experienced a meaningful benefit from the study patches?" Changes in the efficacy end points in the double-blind studies were compared for the women who did and did not experience an overall meaningful benefit. Results. Overall, 33 of 64 women (52%) who received testosterone reported experiencing a meaningful treatment benefit, compared with 21 of 68 women (31%) who received placebo (P = 0.025). Among the women who identified themselves as experiencing a meaningful benefit, the mean (SE) change from baseline in 4-week frequency of satisfying sexual activity was 4.4 (0.76), in desire score was 21.0 (2.78), moving from "seldom" to "sometimes" feeling sexual desire, and in distress score was -36.5 (3.96), moving from "often" to "seldom" being distressed. Among the women who identified themselves as not experiencing a meaningful benefit, the mean (SE) change from baseline in 4-week frequency of satisfying sexual activity was 0.5 (0.31), in desire score was 2.9 (1.42), and in distress score was -8.8 (2.23). Conclusions. Surgically menopausal women with HSDD in these studies received clinically meaningful benefits, including improvements in satisfying sexual activity, sexual desire, and personal distress. C1 Univ Hosp Cleveland, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Procter & Gamble Pharmaceut Inc, Cincinnati, OH USA. Ctr Sexual Med Shappard Pratt, Baltimore, MD USA. RP Kingsberg, S (reprint author), Univ Hosp Cleveland, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Sheryl.Kingsberg@UHhospitals.org NR 25 TC 42 Z9 44 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2007 VL 4 IS 4 BP 1001 EP 1008 DI 10.1111/j.1743-6109.2007.00526.x PN 1 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 188MZ UT WOS:000247925300020 PM 17627745 ER PT J AU Stojanovic, MP Cheng, J Larkin, TM Cohen, SP AF Stojanovic, Milan P. Cheng, Jianguo Larkin, Thomas M. Cohen, Steven P. TI Psychophysical measurements during lumbar discography - A heart rate response study SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE discography; low back pain; heart rate ID LOW-BACK-PAIN; DISC DISRUPTION; SPINE AB Study Design: Prospective clinical data analysis Objective: To determine if heart rate (HR) response correlates with positive discography results. Summary of Background Data: Lumbar discography is a controversial tool for the diagnosis of discogenic low back pain. The subjective nature of discography can make data interpretation difficult, leading to false-positive and false-negative results. HR changes have been found in numerous studies to be a reliable and valid indicator of acute pain. To date, there is no study analyzing the FIR response to discography-induced pain. Methods: The HR measurements were recorded immediately preceding and after contrast injection into the each disc, and statistically correlated with the provocation of concordant pain, nonconcordant pain, and nonpainful discs. Results: Discography was performed in 26 subjects with low back pain. Among 75 discograms, 26 discs elicited concordant pain, 9 provoked nonconcordant pain, and 40 elicited no pain response. There was no significant change in HR during disc stimulation for negative [no pain response (P = 0.19) and nonconcordant (P = 0.26)] discograms, whereas positive discograms [concordant pain (numerical rating scale >= 6/10)] were associated with a statistically significant increase in FIR (P = 0.000002). Conclusions: Lumbar discography induces positive HR response only in positive discograms. Although there is no immediate practical application of these results, 2 implications may deserve future research: (a) correlation of HR response with surgical and intradiscal electrotherapy treatment outcomes; (b) evaluation of HR measurement in cases of false-positive results (concordant pain on discography but no FIR response). C1 Massachusetts Gen Hosp, MGH Pain Ctr, Intervent Pain Program, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Uniformed Serv Univ Hlth Sci, Walter Reed Army Med Ctr, Washington, DC USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. RP Stojanovic, MP (reprint author), Massachusetts Gen Hosp, MGH Pain Ctr, Intervent Pain Program, Dept Anesthesia & Crit Care, ACC-333,Fruit St, Boston, MA 02114 USA. EM mstojanovic@partners.org NR 19 TC 4 Z9 4 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD JUL PY 2007 VL 20 IS 5 BP 387 EP 391 DI 10.1097/BSD.0b013e31802db145 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 188BR UT WOS:000247894000010 PM 17607105 ER PT J AU Born, CT Briggs, SM Ciraulo, DL Frykberg, ER Hammond, JS Hirshberg, A Lhowe, DW O'Neill, PA 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. TI Disasters and mass casualties: I. General principles of response and management SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID TERRORIST BOMBINGS; LESSONS; THREAT AB Disaster planning and response to a mass casualty incident pose unique demands on the medical community. Because they would be required to confront many casualties with bodily injury and surgical problems, surgeons in particular must become better educated in disaster management. Compared with routine practice, triage principles in disasters require an entirely different approach to evaluation and care and often run counter to training and ethical values. An effective response to disaster and mass casualty events should focus on an "all hazards" approach, defined as the ability to adapt and apply fundamental disaster management principles universally to any mass casualty incident, whether caused by people or nature. Organizational tools such as the incident Command System and the Hospital Incident Command System help to effect a rapid and coordinated response to specific situations. The United States federal government, through the National Response Plan, has the responsibility to respond quickly and efficiently to catastrophic incidents and to ensure critical lifesaving assistance. International medical surgical response teams are capable of providing medical, surgical, and intensive care services in austere environments anywhere in the world. C1 Washington Hosp Ctr, ER Inst 1, Washington, DC 20010 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Suny Downstate Med Ctr, Kings Cty Hosp, Div Trauma Surg & Surg Crit Care, Brooklyn, NY 11203 USA. RP Born, CT (reprint author), Washington Hosp Ctr, ER Inst 1, Washington, DC 20010 USA. NR 21 TC 33 Z9 35 U1 1 U2 7 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 JUL PY 2007 VL 15 IS 7 BP 388 EP 396 PG 9 WC Orthopedics SC Orthopedics GA 190YF UT WOS:000248096000004 PM 17602028 ER PT J AU Ingram, L Ehr, I Pina, A AF Ingram, L. Ehr, I. Pina, A. TI Using toyota production system tools to standardize rodent health E-alerts SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 88 EP 88 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000037 ER PT J AU Cooper, DR Quintero, C AF Cooper, D. R. Quintero, C. TI Sentinel monitoring of rodent holding rooms: An alternative approach SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 89 EP 89 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000040 ER PT J AU Taylor, NS Dewhirst, FE Xu, S Clapp, KM Miyamae, J Ng, V Fox, JG AF Taylor, N. S. Dewhirst, F. E. Xu, S. Clapp, K. M. Miyamae, J. Ng, V. Fox, J. G. TI Helicobacter species isolated from the ceca of wild mice as a potential source of infection for mouse colonies SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 89 EP 90 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000041 ER PT J AU Gibbons, C Fuller, JM Jarrell, DM AF Gibbons, C. Fuller, J. M. Jarrell, D. M. TI Work teams and team leaders in laboratory animal care SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 94 EP 94 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000054 ER PT J AU Huang, R Deng, S Wu, Y Min, F Wang, J Li, W Tan, W Wang, Y Huang, P AF Huang, R. Deng, S. Wu, Y. Min, F. Wang, J. Li, W. Tan, W. Wang, Y. Huang, P. TI A nonhuman primate model for evaluation of pathogenesis and immunity to avian influenza a (H5N1) virus SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Guangdong Lab Anim Monitoring Inst, Guangzhou, Peoples R China. Guangdong Med Coll, Zhanjiang, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 4 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 97 EP 98 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000065 ER PT J AU Tonsfeldt, E Hickman, D Van Winkle, DM AF Tonsfeldt, E. Hickman, D. L. Van Winkle, D. M. TI An accessible and humane approach to mouse intubation SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Vet Med Unit, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RI Hickman, Debra/D-3289-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 102 EP 103 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000079 ER PT J AU Sedlacek, RS Becerra, J Yihong, S Fuller, JM Stephen, Y AF Sedlacek, R. S. Becerra, J. Yihong, S. Fuller, J. M. Stephen, Y. TI A common-sense approach to processing cages and bottles SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 124 EP 124 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000146 ER PT J AU Huang, R Wang, Y Liu, Z Yul, Z Deng, S Wu, Q Li, W Min, F Liu, X Huang, P AF Huang, R. Wang, Y. Liu, Z. Yul, Z. Deng, S. Wu, Q. Li, W. Min, F. Liu, X. Huang, P. TI Comparison of the pathogenicity of avian influenza virus a (H5N1) in five mouse strains SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Guangdong Lab Anim Monitoring Inst, Guangzhou, Guangdong, Peoples R China. Guangdong Prov Tradit Chinese Med Hosp, Guangzhou, Guangdong, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 2 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 130 EP 130 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000165 ER PT J AU Le, AT Albo, D Berger, DH AF Le, Anne T. Albo, Daniel Berger, David H. TI Quality of life in the elderly with rectal cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID ABDOMINO-PERINEAL RESECTION; COLORECTAL-CANCER; PREOPERATIVE RADIOTHERAPY; SEXUAL DYSFUNCTION; SURGERY; SURVIVAL; OUTCOMES; IMPACT; INSTRUMENT; MANAGEMENT C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies & Operat, Houston, TX 77030 USA. RP Berger, DH (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Surg 112 OCL,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 53 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUL PY 2007 VL 205 IS 1 BP 124 EP 131 DI 10.1016/j.jamcollsurg.2007.02.028 PG 8 WC Surgery SC Surgery GA 186DD UT WOS:000247758400017 PM 17617341 ER PT J AU Pryor, HI Lange, PA Bader, A Gilbert, J Newman, K AF Pryor, Howard I., II Lange, Patricia A. Bader, Ali Gilbert, James Newman, Kurt TI Multiple magnetic foreign body ingestion: A surgical problem SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article C1 George Washington Univ, Childrens Natl Med Ctr, Dept Gastroenterol & Nutr, Washington, DC 20010 USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Univ N Carolina, Div Pediat Surg, Chapel Hill, NC USA. George Washington Univ, Childrens Natl Med Ctr, Dept Gastroenterol & Nutr, Washington, DC USA. Huntsville Womens & Childrens Hosp, Dept Surg, Huntsville, AL USA. RP Newman, K (reprint author), George Washington Univ, Childrens Natl Med Ctr, Dept Gastroenterol & Nutr, 11 Michigan Ave NW, Washington, DC 20010 USA. NR 10 TC 15 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUL PY 2007 VL 205 IS 1 BP 182 EP 186 DI 10.1016/j.jamcollsurg.2007.01.060 PG 5 WC Surgery SC Surgery GA 186DD UT WOS:000247758400024 PM 17617348 ER PT J AU Lindner, SA Ben Davoren, J Vollmer, A Williams, B Landefeld, CS AF Lindner, Serge A. Ben Davoren, J. Vollmer, Andrew Williams, Brie Landefeld, C. Seth TI An electronic medical record intervention increased nursing home advance directive orders and documentation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE advance directives; electronic medical record; computerized physician order entry; quality improvement; skilled nursing facility ID STATISTICAL QUALITY-CONTROL; LIFE-SUSTAINING TREATMENT; SELF-DETERMINATION ACT; CONTROLLED-TRIAL; CLINICAL REMINDERS; CARE; OUTCOMES; IMPLEMENTATION; PERFORMANCE; STRATEGIES AB OBJECTIVES: To develop an electronic medical record intervention to improve documentation of patient preferences about life-sustaining care, detail of resuscitation and treatment-limiting orders, and concordance between these orders and patient preferences. DESIGN: Prospective before-after intervention trial. SETTING: Veterans Affairs nursing home with an electronic medical record for all clinical information, including clinician orders. PARTICIPANTS: All 224 nursing home admissions from May 1 to October 31, 2004. MEASUREMENTS: Completion of an advance directive discussion note by the primary clinician, clinician orders about resuscitation and other life-sustaining treatments, and concordance between these orders and documented patient preferences. INTERVENTION: The electronic medical record was modified so that an admission order would specify resuscitation status. Additionally, the intervention alerted the primary clinician to complete a templated advance directive discussion note for documentation of life-sustaining treatment preferences. RESULTS: Primary clinicians completed an advance directive discussion note for five of 117 (4%) admissions pre-intervention and 67 of 107 (63%) admissions post-intervention (P <.001). In multivariate analysis, the intervention was independently associated with advance directive discussion note completion (odds ratio=42, 95% confidence interval=15-120). Of patients who preferred do-not-resuscitate (DNR) status, a DNR order was written for 86% pre-intervention versus 98% post-intervention (P=.07); orders to limit other life-sustaining treatments were written for 16% and 40%, respectively (P=.01). CONCLUSIONS: A targeted electronic medical record intervention increased completion of advance directive discussion notes in seriously ill patients. For patients who preferred DNR status, the intervention also increased the frequency of DNR orders and of orders to limit other life-sustaining treatments. C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Lindner, SA (reprint author), Ctr Senior Hlth, 3015 Squalicum Pkwy,Ste 100, Bellingham, WA 98225 USA. EM linserge@yahoo.com FU NIA NIH HHS [AG000912, AG000212] NR 34 TC 19 Z9 19 U1 4 U2 5 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 JUL PY 2007 VL 55 IS 7 BP 1001 EP 1006 DI 10.1111/j.1532-5415.2007.01214.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 183YA UT WOS:000247607100004 PM 17608871 ER PT J AU Evans-Molina, C Regan, S Henault, LE Hylek, EM Schwartz, GR AF Evans-Molina, Carmella Regan, Susan Henault, Lori E. Hylek, Elaine M. Schwartz, Gregory R. TI The new medicare part D prescription drug benefit: An estimation of its effect on prescription drug costs in a medicare population with atrial fibrillation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Medicare Part D; insurance; pharmaceutical services; prescription; drug; atrial fibrillation ID PREVALENCE AB OBJECTIVES: To compare prescription drug cost savings under the most commonly selected Medicare Part D prescription plan in 2006 with savings under the Medicare standard benefit and with drug costs assuming no coverage in an elderly cohort of patients. DESIGN: Inception cohort study. SETTING: An academic medical center. PARTICIPANTS: Four hundred seventy-two patients aged 65 and older who were followed as part of a larger study assessing stroke prevention in patients with atrial fibrillation. MEASUREMENTS: Prescription drug expenditures were calculated for each patient in the cohort under three conditions: the 2006 AARP-endorsed prescription drug plan, the Medicare standard benefit, and no prescription drug coverage. RESULTS: Total prescriptions drug costs were lower under the AARP plan, yet patients paid a similar percentage of total costs under the AARP plan and the Medicare standard benefit. Using different cost assessments, 27% to 46% of patients entered the "doughnut hole" in the AARP plan, and 3% to 11% emerged to receive catastrophic coverage. CONCLUSION: Both the AARP-sponsored and standard Medicare Part D prescription drug benefit programs offer significant savings to enrollees. A greater savings is achieved under the private AARP drug insurance plan, largely due to greater discounts reflected in the negotiated drug prices. A substantial portion of enrollees enter but do not emerge from the coverage gap. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med,Dept Med, Boston, MA 02114 USA. Univ Virginia, Dept Med, Div Endocrinol & Metab, Charlottesville, VA USA. Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. RP Schwartz, GR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med,Dept Med, 50 Staniford St,Suite 300, Boston, MA 02114 USA. EM gschwartz@partners.org FU NIDDK NIH HHS [F32 DK076450, F32 DK076450-01] NR 16 TC 7 Z9 7 U1 1 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 JUL PY 2007 VL 55 IS 7 BP 1038 EP 1043 DI 10.1111/j.1532-5415.2007.01285.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 183YA UT WOS:000247607100009 PM 17608876 ER PT J AU Boockvar, KS Burack, OR AF Boockvar, Kenneth S. Burack, Orah R. TI Organizational relationships between nursing homes and hospitals and quality of care during hospital-nursing home patient transfers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nursing homes; hospitals; organizational affiliation; patient transfer; safety management ID TRANSITIONAL CARE; POSTHOSPITAL CARE; INPATIENT; SETTINGS; OUTCOMES; SAFETY; NEEDS; OLDER AB OBJECTIVES: To identify organizational factors and hospital and nursing home organizational relationships associated with more-effective processes of care during hospital-nursing home patient transfer. DESIGN: Mailed survey. SETTING: Medicare- or Medicaid-certified nursing homes in New York State. PARTICIPANTS: Nursing home administrators, with input from other nursing home staff. MEASUREMENTS: Key predictor variables were travel time between the hospital and the nursing home, affiliation with the same health system, same corporate owner, trainees from the same institution, pharmacy or laboratory agreements, continuous physician care, number of beds in the hospital, teaching status, and frequency of geriatrics specialty care in the hospital. Key dependent variables were hospital-to-nursing home communication, continuous adherence to healthcare goals, and patient and family satisfaction with hospital care. RESULTS: Of 647 questionnaires sent, 229 were returned (35.4%). There was no relationship between hospital-nursing home interorganizational relationships and communication, healthcare goal adherence, and satisfaction measures. Geriatrics specialty care in the hospital (r=0.157; P=.04) and fewer hospital beds (r=-0.194; P=.01) were each associated with nursing homes more often receiving all information needed to care for patients transferred from the hospital. Teaching status (r=0.230; P=.001) and geriatrics specialty care (r=0.185; P=.01) were associated with hospital care more often consistent with healthcare goals established in the nursing home. CONCLUSION: No management-level organizational relationship between nursing home and hospital was associated with better hospital-to-nursing home transfer process of care. Geriatrics specialty care and characteristics of the hospital were associated with better hospital-to-nursing home transfer processes. C1 James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. Jewish Home & Hosp Lifecare Syst, New York, NY USA. Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 NR 30 TC 15 Z9 15 U1 0 U2 5 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 JUL PY 2007 VL 55 IS 7 BP 1078 EP 1084 DI 10.1111/j.1532-5415.2007.01235.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 183YA UT WOS:000247607100015 PM 17608882 ER PT J AU Jung, S Colernan, A Weintraub, NT AF Jung, Susan Colernan, Anne Weintraub, Nancy T. TI Vision screening in the elderly SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review ID QUALITY-OF-LIFE; NURSING-HOME RESIDENTS; VISUAL IMPAIRMENT; CATARACT-SURGERY; OLDER-ADULTS; DIABETIC-RETINOPATHY; HIP FRACTURE; PRIMARY-CARE; EYE DISEASE; POPULATION C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst & Geriatr R, Sepulveda, CA USA. UCLA Multicampus Program Geriatr & Gerontol, Los Angeles, CA USA. RP Weintraub, NT (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Geriatr Med, 16111 Plummer St 11E, Sepulveda, CA 91343 USA. EM nancy.weintraub@va.gov NR 46 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUL PY 2007 VL 8 IS 6 BP 355 EP 362 DI 10.1016/j.jamda.2007.01.096 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 191NY UT WOS:000248139200004 PM 17619034 ER PT J AU Glassman, PA Belperio, P Lanto, A Simon, B Valuck, R Sayers, J Lee, M AF Glassman, Peter A. Belperio, Pamela Lanto, Andrew Simon, Barbara Valuck, Robert Sayers, Jeffrey Lee, Martin TI The utility of adding retrospective medication profiling to computerized provider order entry in an ambulatory care population SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the VA HSR & D CY MAR 09-11, 2004 CL Washington, DC ID ADVERSE DRUG EVENTS; HOSPITALIZED-PATIENTS; PHYSICIAN; SYSTEMS; ALERTS; ERRORS; INTERVENTION; OUTPATIENTS; PREVENTION; MORTALITY AB Background: We assessed whether medication safety improved when a medication profiling program was added to a computerized provider order entry system. Design: Between June 2001 and January 2002 we profiled outpatients with potential prescribing errors using computerized retrospective drug utilization software. We focused primarily on drug interactions. Patients were randomly assigned either to Provider Feedback or to Usual Care. Subsequent adverse drug event (ADE) incidence and other outcomes, including ADE preventability and severity, occurring up to 1 year following the last profiling date were evaluated retrospectively by a pharmacist blinded to patient assignment. Measurements: Data were abstracted using a study-designed instrument. An ADE was defined by an Adverse Drug Reaction Probability scale score of I or more. Statistical analyses included negative binomial regression for comparing ADE incidence. Results: Of 913 patients in the analytic sample, 371 patients (41%) had one or more ADEs. Incidence, by individual, was not significantly different between Usual Care and Provider Feedback groups (37% vs. 45%; p = 0.06; Coefficient, 0.19; 95% CI: -0.008, 0.390). ADE severity was also similar. For example, 51% of ADEs in the Usual Care and 58% in the Provider Feedback groups involved symptoms that were not serious (95% CI for the difference, -15%, 2%). Finally, ADE preventability did not differ. For example, 16% in the Usual Care group and 17% in the Provider Feedback group had an associated warning (95% Cl for the difference, -7 to 5%; p = 0.79). Conclusion: Medications safety did not improve with the addition of a medication profiling program to an electronic prescribing system. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, Los Angeles, CA 90073 USA. VA HSR & D Ctr Excellence Study Healthcare Provid, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Publ Hlth Strateg Healthcare Grp Ctr Qual Mana, Palo Alto, CA USA. VA Ctr Medicat Safety, Hines, IL USA. Univ Colorado, Dept Clin Pharm, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Glassman, PA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, W Los Angeles Campus,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Peter.Glassman@va.gov NR 35 TC 6 Z9 6 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2007 VL 14 IS 4 BP 424 EP 431 DI 10.1197/jamia.M2313 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 191AU UT WOS:000248103000007 PM 17460134 ER PT J AU Handler, SM Altman, RL Perera, S Hanlon, JT Studenski, SA Bost, JE Saul, MI Fridsma, DB AF Handler, Steven M. Altman, Richard L. Perera, Subashan Hanlon, Joseph T. Studenski, Stephanie A. Bost, James E. Saul, Melissa I. Fridsma, Douglas B. TI A systematic review of the performance characteristics of clinical event monitor signals used to detect adverse drug events in the hospital setting SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID PHYSICIAN ORDER ENTRY; COMPUTER-BASED MONITOR; INFORMATION-TECHNOLOGY; DECISION-SUPPORT; NATIONAL ACTION; HEALTH-CARE; HELP SYSTEM; QUALITY; COSTS; SURVEILLANCE AB Objective: We conducted a systematic review of pharmacy and laboratory signals used by clinical event monitor systems to detect adverse drug events (ADEs) in adult hospitals. Design and Measurements: We searched the MEDLINE, CINHAL, and EMBASE databases for the years 19852006, and found 12 studies describing 36 unique ADE signals (10 medication levels, 19 laboratory values, and 7 antidotes). We were able to calculate positive predictive values (PPVs) and 95% confidence intervals (CIs) for 15 signals. Results: We found that PPVs ranged from 0.03 (95% Cl, 0.03-0.03) for hypokalemia, to 0.50 (95% CI, 0.39-0.61) for supratherapeutic quinidine level. In general, antidotes (range = 0.09-0.11) had the lowest PPVs, followed by laboratory values (range = 0.03-0.27) and medication levels (range = 0.03-0.50). Conclusion: Data from this study should help clinical information system and computerized decision support producers develop or improve existing clinical event monitor systems to detect ADEs in their own hospitals by prioritizing those signals with the highest PPVs. C1 VAPHS, Div Clin Geriatr, Dept Med, Sch Med, Pittsburgh, PA USA. VAPHS, Dept Biomed Informat, Sch Med, Pittsburgh, PA USA. VAPHS, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. VAPHS, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA USA. VAPHS, Ctr Res Hlth Care, Dept Med, Pittsburgh, PA USA. VAPHS, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. RP Handler, SM (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr Med, 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM handlersm@upmc.edu OI Handler, Steven/0000-0002-3940-3224 FU NCATS NIH HHS [UL1 TR000005, KL2 TR000146]; NIA NIH HHS [5T32AG021885, P30 AG024827, P30AG024827, R01 AG027017, R01AG027017, T32 AG021885]; NICHD NIH HHS [K12 HD049109] NR 81 TC 43 Z9 47 U1 9 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2007 VL 14 IS 4 BP 451 EP 458 DI 10.1197/jamia.M2369 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 191AU UT WOS:000248103000010 PM 17460130 ER PT J AU McMurry, AJ Gilbert, CA Reis, BY Chueh, HC Kohane, IS Mandl, KD AF McMurry, Andrew J. Gilbert, Clint A. Reis, Ben Y. Chueh, Henry C. Kohane, Isaac S. Mandl, Kenneth D. TI A self-sealing, distributed information architecture for public health, research, and clinical care SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID SURVEILLANCE; EPIDEMIOLOGY; SYSTEM AB Objective: This study sought to define a scalable architecture to support the National Health Information Network (NHIN). This architecture must concurrently support a wide range of public health, research, and clinical care activities. Study Design: The architecture fulfils five desiderata: (1) adopt a distributed approach to data storage to protect privacy, (2) enable strong institutional autonomy to engender participation, (3) provide oversight and transparency to ensure patient trust, (4) allow variable levels of access according to investigator needs and institutional policies, (5) define a self-scaling architecture that encourages voluntary regional collaborations that coalesce to form a nationwide network. Results: Our model has been validated by a large-scale, multi-institution study involving seven medical centers for cancer research. It is the basis of one of four open architectures developed under funding from the Office of the National Coordinator of Health Information Technology, fulfilling the biosurveillance use case defined by the American Health Information Community. The model supports broad applicability for regional and national clinical information exchanges. Conclusions: This model shows the feasibility of an architecture wherein the requirements of care providers, investigators, and public health authorities are served by a distributed. model that grants autonomy, protects privacy, and promotes participation. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Childrens Hosp,Informat Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP McMurry, AJ (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, Childrens Hosp,Informat Program, 300 Longwood Ave,Enders Room 150, Boston, MA 02115 USA. EM amcmurry@chip.org RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NCI NIH HHS [5P30CA06516-40, P30 CA006516]; NLM NIH HHS [1 R01 LM007677-01, N01-LM-3-3515, R01 LM007677]; ODCDC CDC HHS [P01 CD000260, P01 CD000260-01] NR 38 TC 32 Z9 32 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2007 VL 14 IS 4 BP 527 EP 533 DI 10.1197/jamia.M2371 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 191AU UT WOS:000248103000018 PM 17460129 ER PT J AU Zhang, SL Chen, YW Tran, S Chenier, I Hebert, MJ Ingelfinger, JR AF Zhang, Shao-Ling Chen, Yun-Wen Tran, Stella Chenier, Isabelle Hebert, Marie-Josee Ingelfinger, Julie R. TI Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PROXIMAL TUBULAR CELLS; RENAL-COLOBOMA SYNDROME; BRANCHING MORPHOGENESIS; ANGIOTENSINOGEN GENE; GROWTH RESTRICTION; NEPHRON ENDOWMENT; ENDOTHELIAL-CELLS; DIABETIC MOTHERS; EMBRYONIC KIDNEY; PAX-2 EXPRESSION AB Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal D-glucose (5 mM) or high D-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high D-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as D-mannitol, L-glucose, and 2-deoxy-D-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression. C1 Univ Montreal, Ctr Hosp Univ Montreal Hotel Dieu, Montreal, PQ H2W 1T7, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Zhang, SL (reprint author), Univ Montreal, Ctr Hosp Univ Montreal Hotel Dieu, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T7, Canada. EM shao.ling.zhang@umontreal.ca NR 50 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2007 VL 18 IS 7 BP 2105 EP 2115 DI 10.1681/ASN.2006101124 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 200JA UT WOS:000248758500019 PM 17538188 ER PT J AU Lin, SC Lee, WS Ma, JL Shih, KS Mudgal, CS AF Lin, Shang-Chih Lee, Wei-Shiun Ma, Ju-Lung Shih, Kao-Shang Mudgal, Chaitanya S. TI Influence of jig design on biomechanical evaluation of spinal construct stability SO JOURNAL OF THE CHINESE INSTITUTE OF ENGINEERS LA English DT Article DE lumbar; fixator; stability; biomechanical ID LUMBAR INTERBODY FUSION; FIXATION; MODEL; INSTRUMENTATION AB The biomechanical evaluation of spinal construct stability is of clinical importance as the results of such an evaluation provide information about the implant's performance in vivo in stabilizing the spine. The flexion/extension test is critical for the evaluation of spinal stability. However, it is more technically demanding to flex the spinal construct with the more structurally complex jig assembly than the assembly used in the compressive or twisting stability tests. A review of the literature shows that a variety of jig assemblies have been used to investigate the mechanical and kinematic behaviors of spinal constructs. However, there is little consensus about the influence of jig design on the investigated behaviors. The Current study used the elastic beam-column theory to predict the load and deformation of the spinal construct among four possible jig assemblies. The suitability of these four jig assemblies for the short- and long-segment spinal construct was evaluated in detail with three indices: lateral deflection, loading condition, and failures at the bone-screw interfaces. Among the four assemblies, the jig assembly that 0enerates the distally increasing flexion moment and free cephalic motion was suitable for short-segment fixation. The jig assembly that generates the constant flexion moment Seemed to be more appropriate for long-segmentation cases with physiologically acceptable deflection. This study aims to provide an insight into what jig-related factors are associated with physiologically reliable outcomes of the flexion stability test for lumbar implants. C1 Natl Cent Univ, Inst Biomed Engn, Dept Mech Engn, Tao Yuan 320, Taiwan. Natl Taiwan Univ Sci & Technol, Dept Mech Engn, Taipei 106, Taiwan. Far Eastern Mem Hosp, Div Orthopaed Surg, Taipei, Taiwan. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Lin, SC (reprint author), Natl Cent Univ, Inst Biomed Engn, Dept Mech Engn, Tao Yuan 320, Taiwan. EM scorelin@ms28.hinet.net NR 20 TC 0 Z9 0 U1 0 U2 2 PU CHINESE INST ENGINEERS PI TAIPEI PA #1, 4TH FL, SEC 2, JEN-AI RD, TAIPEI 10019, TAIWAN SN 0253-3839 J9 J CHIN INST ENG JI J. Chin. Inst. Eng. PD JUL PY 2007 VL 30 IS 5 BP 891 EP 898 DI 10.1080/02533839.2007.9671315 PG 8 WC Engineering, Multidisciplinary SC Engineering GA 195FE UT WOS:000248397100012 ER PT J AU Schmahmann, JD Pandya, DN AF Schmahmann, Jeremy D. Pandya, Deepak N. TI Cerebral white matter - Historical evolution of facts and notions concerning the organization of the fiber pathways of the brain SO JOURNAL OF THE HISTORY OF THE NEUROSCIENCES LA English DT Review DE fiber tracts; pathways; bundles; fasciculi; history; anatomy; brain white; matter; cognition ID SUPERIOR TEMPORAL SULCUS; CENTRAL NERVOUS-SYSTEM; BLUE REACTION-PRODUCT; RHESUS-MONKEY; BASIS PONTIS; PREFRONTAL CORTEX; FRONTAL-LOBE; PARAHIPPOCAMPAL PROJECTIONS; FUNCTIONAL-ORGANIZATION; CORTICAL CONNECTIONS AB Gross and microscopic studies by early investigators led the cerebral white matter from being regarded as an amorphous mass to an intricately organized system of fasciculi that facilitate the highest expression of cerebral activity. Here we pay homage to the anatomists whose observations resulted in the evolution of ideas about the cerebral white matter. We also draw attention to limitations of the earlier methodologies and to some of the conflicts and controversies that have characterized this field and that persist in the current literature. We conclude with brief reference to the principles of organization of the fiber pathways derived from our studies in the monkey using the autoradiographic tract tracing technique, another step in the ongoing investigations of the cerebral white matter. This historical review has contemporary relevance because the fiber pathways of the brain are crucial components of the distributed neural circuits that subserve nervous system,function; the clinical manifestations of white matter damage are recognized with greater frequency and clarity; and magnetic resonance imaging tractography has made it possible to view these fiber bundles within the living human brain. C1 Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, CPZS-340,55 Fruit St, Boston, MA 02114 USA. NR 174 TC 27 Z9 28 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0964-704X J9 J HIST NEUROSCI JI J. Hist. Neurosci. PD JUL-SEP PY 2007 VL 16 IS 3 BP 237 EP 267 DI 10.1080/09647040500495896 PG 31 WC History & Philosophy Of Science; Neurosciences SC History & Philosophy of Science; Neurosciences & Neurology GA 196TE UT WOS:000248504300001 PM 17620190 ER PT J AU Rim, CS Kim, P Yun, SH AF Rim, Cheon-Seog Kim, Philhan Yun, Seok-Hyun TI Design of an endoscope objective lens with a high numerical aperture and a minimally-invasive outer diameter SO JOURNAL OF THE KOREAN PHYSICAL SOCIETY LA English DT Article DE microendoscopy; endoscope objective lens; graded-index lens; GRIN lens ID CONFOCAL REFLECTANCE MICROSCOPE; IN-VIVO; LYMPH-NODES; LYMPHANGIOGENESIS; TRAFFICKING; METASTASIS; SYSTEM; CANCER; TISSUE; CELLS AB Graded-index (GRIN) objective lenses are very simple in construction and easily secure a proper overall length to diagnose some defects beneath the skin for medical treatment. However, graded-index objective lenses have a limitation of numerical aperture (NA) that directly relates to the optical resolution. These lenses work well under a NA of 0.25, at best, which is free from spherical aberration. We present an endoscope objective lens composed of graded-index lenses with an adaptor that can correct the spherical aberration of GRIN rods with a high numerical aperture of 0.5 and a minimally-invasive outer diameter of 1 mm. That is, by attaching a simple adaptor on the GRIN rods, the endoscope objective lens has an optically diffraction-limited performance for 0.5 NA, which makes the manufacture easier and less expensive. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Rim, CS (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR822, Boston, MA 02114 USA. EM csrim@hannam.ac.kr NR 26 TC 3 Z9 3 U1 0 U2 0 PU KOREAN PHYSICAL SOC PI SEOUL PA 635-4, YUKSAM-DONG, KANGNAM-KU, SEOUL 135-703, SOUTH KOREA SN 0374-4884 J9 J KOREAN PHYS SOC JI J. Korean Phys. Soc. PD JUL PY 2007 VL 51 IS 1 BP 52 EP 64 PG 13 WC Physics, Multidisciplinary SC Physics GA 190ML UT WOS:000248062900011 ER PT J AU Fenton, SH Badgett, RG AF Fenton, Susan H. Badgett, Robert G. TI A comparison of primary care information content in UpToDate and the National Guideline Clearinghouse SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY OCT, 2005 CL Washington, DC SP Amer Med Informat Assoc ID CLINICAL QUESTIONS; PATIENT-CARE; DOCTORS AB Objectives: The study sought to determine if two major resources for primary care questions have significant differences in information content and whether the number of documents found differs by disease category, patient age, or patient gender. Methods: Seven hundred fifty-two questions were randomly selected from the Clinical Questions Collection of the National Library of Medicine. UpToDate and the National Guidelines Clearinghouse (NGC) were searched utilizing keywords from the questions. The number of documents retrieved for each question in the resources was recorded. Chi-squared analysis was used to compare differences in retrieval between the resources. Logistic regression was used to evaluate the effect of patient age, patient gender, or disease category on the ability to find content. Results: UpToDate returned 1 or more documents for 580 questions, while NGC returned at least 1 document for 493 questions (77.1% versus 65.5% of question sampled, P = 0.001). In combination, the 2 resources returned content for 91% of searches (n = 685). NGC retrieved a mean of 16.3 documents per question versus 8.7 documents from UpToDate. Disease category was the only variable having a significant impact on the presence of online resource content. Conclusions: UpToDate had greater breadth of content than NGC, while neither resource provided complete coverage. Current practice guidelines, as reflected by those in the NGC, addressed at most two-thirds of the selected clinical questions. C1 Texas A&M Univ, Hlth Sci Ctr, Dept Hlth Policy & Management, Sch Rural Publ Hlth, San Antonio, TX 78248 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, ALMD, San Antonio, TX 78229 USA. RP Fenton, SH (reprint author), Texas A&M Univ, Hlth Sci Ctr, Dept Hlth Policy & Management, Sch Rural Publ Hlth, 21 Inwood Manor, San Antonio, TX 78248 USA. EM shfenton@srph.tamhsc.edu; badgett@uthscsa.edu OI Badgett, Robert/0000-0003-2888-3303 NR 20 TC 11 Z9 11 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 255 EP 259 DI 10.3163/1536-5050.95.3.255 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300009 PM 17641755 ER PT J AU Ozcan, A Bilenca, A Desjardins, AE Bouma, BE Tearney, GJ AF Ozcan, Aydogan Bilenca, Alberto Desjardins, Adrien E. Bouma, Brett E. Tearney, Guillermo J. TI Speckle reduction in optical coherence tomography images using digital filtering SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID RADAR IMAGES; NOISE; ENHANCEMENT; SUPPRESSION; BIOPSY AB Speckle noise is a ubiquitous artifact that limits the interpretation of optical coherence tomography images. Here we apply various speckle-reduction digital filters to optical coherence tomography images and compare their performance. Our results indicate that shift-invariant, nonorthogonal wavelet-transform-based filters together with enhanced Lee and adaptive Wiener filters can significantly reduce speckle and increase the signal-to-noise ratio, while preserving strong edges. The speckle reduction capabilities of these filters are also compared with speckle reduction from incoherent angular compounding. Our results suggest that by using these digital filters, the number of individual angles required to attain a certain level of speckle reduction can be decreased. (c) 2007 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Ozcan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM aozcan@mgh.harvard.edu FU NCI NIH HHS [R01 CA103769, R01 CA103769-03] NR 45 TC 101 Z9 103 U1 3 U2 15 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 EI 1520-8532 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD JUL PY 2007 VL 24 IS 7 BP 1901 EP 1910 DI 10.1364/JOSAA.24.001901 PG 10 WC Optics SC Optics GA 189ES UT WOS:000247972800009 PM 17728812 ER PT J AU Sarkey, JP Richards, MP Stubbs, EB AF Sarkey, J. P. Richards, M. P. Stubbs, E. B., Jr. TI Lovastatin attenuates nerve injury in an animal model of Guillain-Barre syndrome SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Annual Meeting of the Peripheral-Nerve-Society CY JUL 14-18, 2007 CL Snowbird, UT SP Peripheral Nerve Soc C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 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 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUL PY 2007 VL 12 SU 1 BP 76 EP 76 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 207IA UT WOS:000249243600206 ER PT J AU Shankarappa, SA Sarkey, JP Richards, MP Stubbs, EB AF Shankarappa, S. A. Sarkey, J. P. Richards, M. P. Stubbs, E. B., Jr. TI Forced-exercise protects against the development of early tactile hyperalgesia in experimental diabetes SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Annual Meeting of the Peripheral-Nerve-Society CY JUL 14-18, 2007 CL Snowbird, UT SP Peripheral Nerve Soc C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUL PY 2007 VL 12 SU 1 BP 79 EP 80 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 207IA UT WOS:000249243600216 ER PT J AU de Moya, MA Seaver, C Spaniolas, K Inaba, K Nguyen, M Veltman, Y Shatz, D Alain, HB Pizano, L AF de Moya, Marc A. Seaver, Christopher Spaniolas, Konstantinos Inaba, Kenji Nguyen, Michael Veltman, Yevgeniy Shatz, David Alain, Hasan B. Pizano, Lotus TI Occult pneurnothorax in trauma patients: Development of an objective scoring system SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Western-Trauma-Association CY FEB 26-MAR 03, 2006 CL Big Sky, MT SP Western Trauma Assoc DE pneumothorax; occult; pneumothorax; trauma; pneumothorax scoring ID TUBE THORACOSTOMY; PNEUMOTHORAX; CT; MANAGEMENT; SCANS AB Background: The incidence of occult pneumothorax (OPTX) has dramatically increased since the widespread use of computed tomography (CT) scanning. The OPTX is defined as a pneumothorax not identified on plain chest X-ray but detected by CT scan. The overall reported incidence is about 5% to 8% of all trauma patients. We conducted a 5-year review of our OPTX incidence and asked if an objective score could be developed to better quantify the OPTX. This in turn may guide the practitioner with the decision to observe these patients. Methods: This is a retrospective review of all trauma patients in a Level I university trauma center during a 5-year period. The patients were identified by a query of all pneumothoraces in our trauma registry. Those X-ray results were then reviewed to identify those who had OPTX. After developing an OPTX score on a small number, we retrospectively scored 50 of the OPTXs by taking the largest perpendicular distance in millimeters from the chest wall of the largest air pocket. We then added 10 or 20 to this if the OPTX was either anterior/posterior or lateral, respectively. Results: A total of 21,193 trauma patients were evaluated and 1,295 patients with pneumothoraces (6.1%) were identified. Of the 1,295 patients with pneumothoraces, 379 (29.5%) OPTXs were identified. The overall incidence of OPTX was 1.8%: 95.7% occurred after blunt trauma, 222 (59%) of the OPTX patients had chest tubes and of the remaining 157 without chest tubes, 27 (17%) were on positive pressure ventilation. Of the 50 studies selected for scoring, the average score was 28.5. The average score for those with chest tubes was 34. The average score for those without chest tubes was 21. The positive predictive value for need of chest tube if the score was > 30 was 78% and the negative predictive value if the score was < 20 was 70%. Area under the receiver operator characteristic curve was 0.72, which was significant with p < 0.007. Conclusion: The OPTX score could quantify the size of the OPTX allowing the practitioner to better define a "small" pneumothorax. The management of OPTX is not standardized and further study using a more objective classification may assist the surgeon's decision-making. The application of a scoring system may also decrease unnecessary insertion of chest tubes for small OPTXs and is currently being prospectively validated. C1 Univ Miami, Ryder Trauma Ctr, Dept Surg, Miami, FL 33152 USA. Massachusetts Gen Hosp, Div Trauma Emergency Surg Surg Crit Care, Boston, MA 02114 USA. Univ So Calif, Los Angeles Cty Hosp, Div Trauma, Los Angeles, CA USA. RP de Moya, MA (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM mdemoya@partners.org NR 13 TC 41 Z9 41 U1 0 U2 1 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 JUL PY 2007 VL 63 IS 1 BP 13 EP 17 DI 10.1097/TA.0b013e31806864fc PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 190MI UT WOS:000248062600004 PM 17622863 ER PT J AU Laing, FC Townsend, BA Rodriguez, JR AF Laing, Faye C. Townsend, Brent A. Rodriguez, J. Ruben TI Ovary-containing hernia in a premature infant - Sonographic diagnosis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID INGUINAL-HERNIAS; FEMALE INFANTS AB In both male and female fetuses, inguinal canal development entails a complex sequence of anatomic events involving the gubernaculum and processus vaginalis. In the normally developing female fetus, the processus vaginalis is usually obliterated by 8 months of gestation.(1) In premature infants, because this structure is often patent, an inguinal hernia commonly develops. In female infants, it has been reported to contain the ovary with or without portions of the fallopian tube 15% to 20% of the time.(2) Although some hernias regress spontaneously,(3) this is less likely to occur if it contains the ovary, and, in comparison to a bowel-containing hernia, the risk of incarceration is greatly increased.(2,4,5) The pediatric and surgical literature have described ovary-containing inguinal hernias in neonates and infants,(1-6) but reports in the ultrasound and radiology literature are lacking. We describe such a case to alert sonographers to its appearance and presentation and to emphasize the pathophysiologic characteristics of this condition in the premature infant. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Laing, FC (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM flaing@partners.org NR 9 TC 10 Z9 11 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 2007 VL 26 IS 7 BP 985 EP 987 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 186TU UT WOS:000247801900017 PM 17592064 ER PT J AU Jones, JE Atkins, MD Brewster, DC Chung, TK Kwolek, CJ LaMuraglia, GM Hodgman, TM Cambria, RP AF Jones, John E. Atkins, Marvin D. Brewster, David C. Chung, Thomas K. Kwolek, Christopher J. LaMuraglia, Glenn M. Hodgman, Thomas M. Cambria, Richard P. TI Persistent type 2 endoleak after endovascular repair of abdominal aortic aneurysm is associated with adverse late outcomes SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; II ENDOLEAK; FOLLOW-UP; NATURAL-HISTORY; CLINICAL-TRIAL; RUPTURE; CONVERSION; SECONDARY; EVAR; INTERVENTION AB Objective: Type 2 endoleak occurs in up to 20% of patients after endovascular aneurysm repair (EVAR), but its long-term significance is debated. We reviewed our experience to evaluate late outcomes associated with type 2 endoleak. Methods: During the interval January 1994 to December 2005, 873 patients underwent EVAR. Computed tomography (CT) scan assessment was performed <= 1 month of the operation and at least annually thereafter. Sequential 6-month CT scan follow-up was adopted for those patients with persistent type 2 endoleaks, and reintervention was limited to those with sac enlargement > 5 mm. Study end points included overall survival, aneurysm sac growth, reintervention rate, conversion to open repair, and abdominal aortic aneurysm (AAA) rupture. Preoperative variables and anatomic factors potentially associated with these endpoints were assessed using multivariate analysis. Results: We identified 164 (18.9%) patients with early (at the first follow-up CT scan) type 2 endoleaks. Mean follow-up was 32.6 months. In 131 (79.9%) early type 2 endoleaks, complete and permanent leak resolution occurred <= 6 months. Endoleaks persisted in 33 patients (3.8% of total patients; 20.1% of early type 2 endoleaks) for > 6 months. Transient type 2 endoleak (those that resolved <= 6 months of EVAR) was not associated with adverse late outcomes. In contrast, persistent endoleak was associated with several adverse outcomes. AAA-related death was not significantly different between patients with and without a type 2 endoleak (P = .78). When evaluating patients with no early endoleak vs persistent endoleak, freedom from sac expansion at 1, 3, and 5 years was 99.2%, 97.6%, and 94.9% (no leak) vs 88.1%, 48.0%, and 28.0% (persistent) (P < .001). Patients with persistent endoleak were at increased risk for aneurysm sac growth vs patients without endoleak (odds ratio [OR], 25.9; 95% confidence interval [CI] 11.8 to 57.4; P < .001). Patients with a persistent endoleak also had a significantly increased rate of reintervention (OR, 19.0; 95% CI, 8.0 to 44.7); P < .001). Finally, aneurysm rupture occurred in 4 patients with type 2 endoleaks. Freedom from rupture at 1, 3, and 5 years for patients with a persistent type 2 endoleak was 96.8%, 96.8%, and 91.1% vs 99.8%, 98.5%, and 97.4% for patients without a type 2 endoleak. Multivariate analysis demonstrated persistent type 2 endoleak to be a significant predictor of aneurysm rupture (P = .03). Conclusions: Persistent type 2 endoleak is associated with an increased incidence of adverse outcomes, including aneurysm sac growth, the need for conversion to open repair, reintervention rate, and rupture. These data suggest that patients with persistent type 2 endoleak (> 6 months) should be considered for more frequent follow-up or a more aggressive approach to reintervention. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02144 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Surg Serv,Div Vasc & Endovasc Surg, Boston, MA 02144 USA. RP Jones, JE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,WAC 458, Boston, MA 02144 USA. EM jjones24@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 35 TC 168 Z9 175 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2007 VL 46 IS 1 BP 1 EP 8 DI 10.1016/j.jvs.2007.02.073 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 185JO UT WOS:000247707500001 PM 17543489 ER PT J AU Crawford, RS Chung, TK Hodgman, T Pedraza, JD Corey, M Cambria, RP AF Crawford, Robert S. Chung, Thomas K. Hodgman, Thomas Pedraza, Juan D. Corey, Michael Cambria, Richard P. TI Restenosis after eversion vs patch closure carotid endarterectomy SO JOURNAL OF VASCULAR SURGERY LA Welsh DT Article; Proceedings Paper CT 33rd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 22-24, 2006 CL Boston, MA SP New England Soc Vasc Surg ID RANDOMIZED-TRIAL; ARTERY STENOSIS; DURABILITY; EXPERIENCE; DISEASE; WOMEN AB Objectives. Recurrent stenosis after carotid endarterectomy (CEA), previously reported to occur in 1%/year after operation, is the finite limitation of CEA. Eversion endarterectomy has a perceived lower incidence of recurrent stenosis, although data to support this contention are conflicting. The goal of the present study was to compare the late anatomic results of patch closure (PC) vs eversion CEA. Methods: Between January 1, 1995 and June 30, 2005, 950 CEA were performed by the senior author with adoption of eversion (EV) as the primary technique as of January 1, 2001. With minimum of 1-year follow-up by study inclusion criteria, complete follow-up data (including a duplex scan) was available for 155 PC and 135 EV patients. Incidence of moderate (50% to 70%) and severe (> 70%) restenosis was examined at <= 2 months and > 1 year after operation. Study end-points included late stroke, survival, and freedom from restenosis (moderate and severe) and were assessed by actuarial methods. Results. There were no differences in relevant demographic/clinical parameters, indication for surgery (69% overall asymptomatic) or early perioperative stroke/death (1.1% overall; P = .25) between PC and EV. After correction for different mean follow-up intervals (PC = 5.5 years vs EV = 3.5 years) by actuarial methods, there was no significant difference in late moderate (P = .91) or severe (P = .54) recurrent stenosis between PC and EV. In the group of patients with at least 1-year follow-up, 11/290 (3.8%) patients (4/135 EV, 7/155 PC; P = .39) required reintervention on their operated carotid artery at a cumulative follow-up interval of 4.5 years. Three strokes (3/290; 1.1%) occurred during late follow-up, all in the PC group, with only one related to the operated carotid artery. Late survival was similar between EV and PC, (P = .86). Female gender (odds ratio [OR] 3.72[1.02-13.5], P = .046) was associated with severe restenosis irrespective of surgical technique. Univariate analysis also showed that female gender (OR 7.6[CI: 0.88-66.7], P = .042) was associated with late stroke. Conclusion: These findings indicate that restenosis rates are similar between eversion and patch CEA and likely represent biological remodeling phenomenon rather than technical variations of operations. While EV offers distinct advantages in certain anatomic circumstances, adoption of EV with the hope of decreasing restenosis is not warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Gen Surg Serv, Cambridge, MA 02138 USA. RP Cambria, RP (reprint author), WACC 448,15 Parkman St, Boston, MA 02114 USA. EM rcambria@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 44 TC 30 Z9 32 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2007 VL 46 IS 1 BP 41 EP 48 DI 10.1016/j.jvs.2007.02.055 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 185JO UT WOS:000247707500008 PM 17606120 ER PT J AU Kougias, P Lin, PH Dardik, A Lee, WA El Sayed, HF Zhou, W AF Kougias, Panagiotis Lin, Peter H. Dardik, Alan Lee, W. Anthony El Sayed, Hosam F. Zhou, Wei TI Successful treatment of endotension and aneurysm sac enlargement with endovascular stent graft reinforcement SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSMS; REPAIR; PRESSURE; EXCLUDER AB Abdominal aortic aneurysm (AAA) enlarges after successful endovascutar repair because of endoleak, which is persistent blood flow within the aneurysm sac. In the absence of detectable endoleak, AAA may still expand, in part because of endotension, which is persistent pressurization within the excluded aneurysm. We report three patients who underwent successful endovascular AAA repair using the Excluder device (W. L. Gore & Associates, Flagstaff, Ariz). Although their postoperative surveillance showed an initial aneurysm regression, delayed aneurysm enlargement developed in all three, apparently due to endotension. Endovascular treatment was performed in which endograft reinforcement with a combination of aortic cuff and iliac endograft extenders were inserted in the previously implanted stent grafts. The endograft reinforcement procedure successfully resulted in aneurysm sac regression in all three patients. Our study underscores the significance of increased graft permeability as a mechanism of endotension and delayed aneurysm enlargement after successful endovascular AAA repair. In addition, our cases illustrate the feasibility and efficacy of an endovascular treatment strategy when endotension and aneurysm sac enlargement develops after endovascular AAA repair. C1 Baylor Coll Med, Div Vasc Surg & Endovasc Thrapy, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Hosp, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Surg, VA Connecticut Hlthcare Syst, New Haven, CT 06520 USA. Univ Florida, Dept Surg, Div Vasc Surg & Endovasc Therapy, Coll Med, Gainesville, FL 32611 USA. RP Lin, PH (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Thrapy, Michael E DeBakey Dept Surg, Houston VAMC, 112,2002 Holocomb Blvd, Houston, TX 77030 USA. EM plin@bcm.cdu NR 14 TC 16 Z9 20 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2007 VL 46 IS 1 BP 124 EP 127 DI 10.1016/j.jvs.2007.02.067 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 185JO UT WOS:000247707500021 PM 17606128 ER PT J AU Beckham, JD Goody, RJ Clarke, P Bonny, C Tyler, KL AF Beckham, J. David Goody, Robin J. Clarke, Penny Bonny, Christophe Tyler, Kenneth L. TI Novel strategy for treatment of viral central nervous system infection by using a cell-permeating inhibitor of c-Jun N-terminal kinase SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; HERPES-SIMPLEX-VIRUS; REOVIRUS-INDUCED APOPTOSIS; PEPTIDE INHIBITOR; ENCEPHALITIS; INJURY; DEATH; JNK; TRANSCRIPTION; INDUCTION AB Viral encephalitis is a major cause of morbidity and mortality worldwide, yet there is no proven efficacious therapy for most viral infections of the central nervous system (CNS). Many of the viruses that cause encephalitis induce apoptosis and activate c-Jun N-terminal kinase (JNK) following infection. We have previously shown that reovirus infection of epithelial cell lines activates JNK-dependent apoptosis. We now show that reovirus infection resulted in activation of JNK and caspase-3 in the CNS. Treatment of reovinis-infected mice with a cell-permeating peptide that competitively inhibits JNK activity resulted in significantly prolonged survival of intracerebrally infected mice following an otherwise lethal challenge with T3D (100 X 501% lethal dose). Protection correlated with reduced CNS injury, reduced neuronal apoptosis, and reduced c-Jun activation without altering the viral titer or viral antigen distribution. Given the efficacy of the inhibitor in protecting mice from viral encephalitis, JNK inhibition represents a promising and novel treatment strategy for viral encephalitis. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Xigen SA, CH-1003 Lausanne, Switzerland. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, 4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIAID NIH HHS [T32 AI007537, T32AI07537]; NINDS NIH HHS [5R01NS050138, R01 NS050138-04, R01 NS051403-03, R01 NS051403, R01 NS050138, 1R01NS051403] NR 40 TC 30 Z9 32 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 JUL PY 2007 VL 81 IS 13 BP 6984 EP 6992 DI 10.1128/JVI.00467-07 PG 9 WC Virology SC Virology GA 180YW UT WOS:000247404900021 PM 17475657 ER PT J AU Utermark, T Schaffhausen, BS Roberts, TM Zhao, JJ AF Utermark, Tamara Schaffhausen, Brian S. Roberts, Thomas M. Zhao, Jean J. TI The p110 alpha isoform of phosphatidylinositol 3-kinase is essential for polyomavirus middle T antigen-mediated transformation SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; TUMOR-ANTIGEN; KINASE-ACTIVITY; PROTEIN PHOSPHATASE-2A; GENE-PRODUCT; CELL-TRANSFORMATION; MUTANT POLYOMAVIRUS; VIRUS MUTANT; BINDING-SITE; RAT-CELLS AB Middle T antigen (MT) of polyomavirus is known to play an important role in virus-mediated cellular transformation. While MT has been extensively examined in spontaneously immortalized rodent fibroblasts, its interactions with cells of other types and species are less well understood. We have undertaken a cross-species and cross-cell-type comparison of MT-induced transformation in cells with genetically defined backgrounds. We tested the transforming abilities of a panel of MT mutants, Y250F, Y315F, and Y322F, that are selectively mutated in the binding sites for the principal effectors of MT-Src homology 2 domain-containing transforming protein, phosphatidylinositol 3-kinase (PI3K), and phospholipase C-gamma, respectively-in fibroblasts and epithelial cells of murine or human origin. We found that the Y315F mutation disabled the ability of MT to induce transformation in all cell types and species tested. While Y315F also failed to activate the PI3K pathway in these cells, genetic evidence has indicated Y315 may make other contributions to transformation. To confirm the role of PI3K, the PIK3CA gene, encoding p110 alpha, the prime effector of PI3K signaling downstream from activated growth factor receptors, was genetically ablated. This abolished the transforming activity of MT, demonstrating the essential role for this PI3K isoform in MT-mediated transformation. The Y250F mutant was able to transform the human, but not the murine, cells that were examined. Interestingly, this mutant fully activates the PI3K pathway in human cells but activated PI3K signaling poorly in the murine cells used in the study. This again points to the importance of PI3K activation for transformation and suggests that the mechanism by which MT activates the PI3K pathway differs in different species. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu FU NCI NIH HHS [P01 CA050661, CA30002, CA34722, P01 CA089021, P01-CA089021, P01-CA50661, R01 CA030002, R01 CA034722, R37 CA030002] NR 55 TC 24 Z9 24 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 JUL PY 2007 VL 81 IS 13 BP 7069 EP 7076 DI 10.1128/JVI.00115-07 PG 8 WC Virology SC Virology GA 180YW UT WOS:000247404900030 PM 17442716 ER PT J AU Mbisa, JL Barr, R Thomas, JA Vandegraaff, N Dorweiler, IJ Svarovskaia, ES Brown, WL Mansky, LM Gorelick, RJ Harris, RS Engelman, A Pathak, VK AF Mbisa, Jean L. Barr, Rebekah Thomas, James A. Vandegraaff, Nick Dorweiler, Irene J. Svarovskaia, Evguenia S. Brown, William L. Mansky, Louis M. Gorelick, Robert J. Harris, Reuben S. Engelman, Alan Pathak, Vinay K. TI Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE TRANSCRIPTION; IN-VIVO; VIF PROTEIN; VIRAL-DNA; RETROVIRAL INFECTION; CYTIDINE DEAMINATION; ANTIVIRAL ACTIVITY; RIBONUCLEASE-H; HIV-1 VIRION; HYPERMUTATION AB Encapsidation of host restriction factor APOBEC3G (A3G) into vif-deficient human immunodeficiency virus type I (HIV-1) blocks virus replication at least partly by C-to-U deamination of viral minus-strand DNA, resulting in G-to-A hypermutation. A3G may also inhibit HIV-1 replication by reducing viral DNA synthesis and inducing viral DNA degradation. To gain further insight into the mechanisms of viral inhibition, we examined the metabolism of A3G-exposed viral DNA. We observed that an overall 35-fold decrease in viral infectivity was accompanied by a five- to sevenfold reduction in viral DNA synthesis. Wild-type A3G induced an additional fivefold decrease in the amount of viral DNA that was integrated into the host cell genome and similarly reduced the efficiency with which HIV-1 preintegration complexes (PICs) integrated into a target DNA in vitro. The A3G C-terminal catalytic domain was required for both of these antiviral activities. Southern blotting analysis of PICs showed that A3G reduced the efficiency and specificity of primer tRNA processing and removal, resulting in viral DNA ends that are inefficient substrates for integration and plus-strand DNA transfer. However, the decrease in plus-strand DNA transfer did not account for all of the observed decrease in viral DNA synthesis associated with A3G. These novel observations suggest that HIV-1 cDNA produced in the presence of A3G exhibits defects in primer tRNA processing, plus-strand DNA transfer, and integration. C1 NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Univ Minnesota, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Biochem Mol Biol & Biophys, Arnold & Mabel Beckman Ctr Transposon Res, Minneapolis, MN 55455 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, SAIC Frederick Inc, POB B,Bldg 535, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov OI Thomas, James/0000-0002-2509-490X FU Intramural NIH HHS; NCI NIH HHS [N01-CO12400, N01CO12400]; NIAID NIH HHS [AI064046, AI39394, AI57735, K02 AI057735, R01 AI039394, R01 AI064046, R37 AI039394, R37 AI064046, R56 AI064046]; NIGMS NIH HHS [GM56615, R01 GM056615, R29 GM056615] NR 54 TC 191 Z9 197 U1 1 U2 9 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 JUL PY 2007 VL 81 IS 13 BP 7099 EP 7110 DI 10.1128/JVI.00272-07 PG 12 WC Virology SC Virology GA 180YW UT WOS:000247404900033 PM 17428871 ER PT J AU Streeck, H Lichterfeld, M Alter, G Meier, A Teigen, N Yassine-Diab, B Sidhu, HK Little, S Kelleher, A Routy, JP Rosenberg, ES Sekaly, RP Walker, BD Altfeld, M AF Streeck, Hendrik Lichterfeld, Mathias Alter, Galit Meier, Angela Teigen, Nickolas Yassine-Diab, Bader Sidhu, Harlyn K. Little, Susan Kelleher, Anthony Routy, Jean-Pierre Rosenberg, Eric S. Sekaly, Rafick-Pierre Walker, Bruce D. Altfeld, Marcus TI Recognition of a defined region within p24 Gag by CD8(+) T cells during primary human immunodeficiency virus type I infection in individuals expressing protective HLA class I alleles SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CELLULAR IMMUNE-RESPONSES; PRIMARY HIV-1 INFECTION; LYMPHOCYTE RESPONSE; VACCINE DESIGN; VIRAL LOAD; ESCAPE; AIDS; VIREMIA; DIVERSITY AB Human immunodeficiency virus type I (HIV-1) -specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8+ T-cell responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-specific T-cell responses between subjects expressing the protective allelle HLA-B27 or -B57 and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects identified during primary HIV-1 infection. CD8+ T cells of individuals expressing HLA-B27 or -B57 targeted a defined region within HIV-1 p24 Gag (amino acids 240 to 272) early in infection, and responses against this region contributed over 35% to the total HIV-1-specific T-cell responses in these individuals. In contrast, this region was rarely recognized in individuals expressing HLA-B35, an HLA allele associated with rapid disease progression, or in subjects expressing neither HLA-B57/B27 nor HLA-B35 (P < 0.0001). The identification of this highly conserved region in p24 Gag targeted in primary infection specifically in individuals expressing HLA class I alleles associated with slower HIV-1 disease progression provides a rationale for vaccine design aimed at inducing responses to this region restricted by other, more common HLA class I alleles. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr,Div AIDS,Infect Dis Unit, Boston, MA 02129 USA. Ctr Rech CHUM, Immunol Lab, Montreal, PQ, Canada. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Darlinghurst, NSW, Australia. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. McGill Univ, Royal Victoria Hosp, Div Hematol & Immunodeficiency Serv, Montreal, PQ H3A 1A1, Canada. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org FU NIAID NIH HHS [AI43638, U01 AI043638, U01 AI052403, R01 AI50429, R01 AI050429] NR 31 TC 80 Z9 84 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 14 BP 7725 EP 7731 DI 10.1128/JVI.00708-07 PG 7 WC Virology SC Virology GA 188UF UT WOS:000247944100037 PM 17494064 ER PT J AU Jang, IK Baron, SJ Hursting, MJ Anglade, E AF Jang, Ik-Kyung Baron, Suzanne J. Hursting, Marcie J. Anglade, Eddy TI Argatroban therapy in women with heparin-induced thrombocytopenia SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ANTICOAGULATION; DYSFUNCTION; THROMBOSIS; GENDER AB Objectives: Women have increased risk of developing heparin-induced thrombocytopenia ( HIT), a serious, immune-mediated prothrombotic condition, and have a worse prognosis when affected. We compared gender differences for treatment and outcomes in HIT patients administered argatroban therapy. Methods: From a multicenter retrospective registry of argatroban-treated patients, we identified females (n = 42) and males (n = 50) with clinically diagnosed HIT who were administered argatroban <= 10 mu g/kg/min. Upon diagnosis of HIT, heparin was discontinued. Continuous intravenous argatroban was instituted, adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline. Between-gender comparisons were made of argatroban dosing, aPTT responses, and clinical outcomes (death, amputation, new thrombosis, major bleeding). Results: At baseline, females and males were generally well matched, excepting platelet count (medians, 101 x 10(9)/L vs. 170 x 10(9)/L vs. p = 0.01), with 9 (21%) females and 19 (38%) males having HIT-related thrombosis. Typically, argatroban was initiated and maintained at 1.0-1.1 mu g/kg/min for approximately 6 days, irrespective of gender. No differences were detected between females and males in aPTTs during therapy ( respective medians, 57.3 vs. 59.5 seconds) or time to therapeutic aPTTs (7.3 vs. 10.3 hours), or platelet count recovery (2.5 vs. 7.4 days). Of patients with available data, 20 of 35 (57%) females and 19 of 35 (54%) males were converted to warfarin. The composite end point of death, amputation, or new thrombosis within 37 days of argatroban initiation occurred in 10 (24%) females and 8 (16%) males (p = 0.43). Within 37 days, 7 (17%) females and 7 (14%) males died (2 while on argatroban), 1 (2%) female required amputation ( off argatroban), and 3 (7%) females and 2 (4%) males developed new thrombosis (3 while on argatroban). Major bleeding occurred in 1 (2%) female and 1 (2%) male. Conclusions: Argatroban can be used effectively and safely to manage HIT in females, with dosing requirements, aPTT responses, and clinical outcomes comparable to those in men. Future, larger studies are warranted in establishing the unique characteristics of HIT in females. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Sci Consulting, Austin, TX USA. CTI Clin Trial & Consulting Serv, Blue Ash, OH USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 843, Boston, MA 02114 USA. EM ijang@partners.org NR 26 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL PY 2007 VL 16 IS 6 BP 895 EP 901 DI 10.1089/jwh.2006.0167 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 197JR UT WOS:000248551600013 PM 17678460 ER PT J AU Sims, RV Ahmed, A Sawyer, P Allman, RM AF Sims, Richard V. Ahmed, Ali Sawyer, Patricia Allman, Richard M. TI Self-reported health and driving cessation in community-dwelling older drivers SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID INCREASED DEPRESSIVE SYMPTOMS; RATED HEALTH; PREDICTORS; DISABILITY; ADULTS; AGE AB Background. Stopping driving has significant negative consequences for older adults, but there is no simple, reliable screening tool to predict driving cessation. We sought to determine if self-rated health (SRH) was an independent predictor of driving cessation among older adults. Methods. Data on SRH (poor, fair, good, very good, or excellent), medical diagnoses, physical performance, visual acuity, driving status, and other relevant covariates were collected from 649 community-dwelling older Alabama drivers during in-home interviews. Using multivariable logistic regression analyses, we estimated the association of SRH with driving cessation 2 years later. Results. Participants had a mean age of 74 years; 43% were women, 41 % African American, and 48% rural. Overall, 36% reported poor to fair SRH at baseline, and 11 % had stopped driving after 2 years. Compared to 8% of drivers with good to excellent SRH, 17% with poor to fair health stopped driving (adjusted odds ratio [OR], 1.93; 95% confidence interval [CI], 1.09-3.41; p = .025). Lower Short Physical Performance Battery (SPPB) scores (adjusted OR, 0.86; 95% CI, 0.78-0.95; p = .001) and older age (adjusted OR, 1.06 per year; 95% CI, 1.01-1.11; p =.010) were also associated with driving cessation. Receiver operating characteristics curves documented similar predictive discrimination (c statistics) for SRH (0.72), the SPPB (0.70), and a count of comorbidities based on the Charlson Comorbidity Index (0.73). Conclusions. Poor to fair SRH predicted incident driving cessation after 2 years in a cohort of older adults. SRH can be easily obtained during clinic visits to identify at-risk drivers. C1 [Sims, Richard V.; Ahmed, Ali; Allman, Richard M.] Birmingham Atlanta GRECC, Birmingham, AL 35233 USA. [Sims, Richard V.; Ahmed, Ali; Allman, Richard M.] Birmingham VA Med Ctr, Birmingham, AL USA. [Sims, Richard V.; Ahmed, Ali; Sawyer, Patricia; Allman, Richard M.] Univ Alabama, Ctr Aging, Birmingham, AL USA. [Sims, Richard V.; Ahmed, Ali; Sawyer, Patricia; Allman, Richard M.] Univ Alabama, Div Geriatr Geriatr & Palliat Care, Birmingham, AL USA. RP Sims, RV (reprint author), Birmingham Atlanta GRECC, Room 8B-8213,700 19th St S, Birmingham, AL 35233 USA. EM richard.sims@med.va.gov RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 FU NIA NIH HHS [K23 AG019211, AG15062, 1-K23-AG19211-04, K23 AG019211-04] NR 23 TC 17 Z9 17 U1 0 U2 3 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2007 VL 62 IS 7 BP 789 EP 793 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AB UT WOS:000253828700015 PM 17634328 ER PT J AU Shankland, SJ Pippin, JW Reiser, J Mundel, P AF Shankland, S. J. Pippin, J. W. Reiser, J. Mundel, P. TI Podocytes in culture: past, present, and future SO KIDNEY INTERNATIONAL LA English DT Review DE podocyte biology; cultivation of differentiated podocytes; differentiation markers; proteinuric kidney diseases ID GLOMERULAR EPITHELIAL-CELLS; ALPHA-PARVIN COMPLEX; RAT-KIDNEY; IN-VITRO; NEPHROTIC-SYNDROME; SLIT DIAPHRAGM; GROWTH-FACTOR; ANGIOTENSIN SYSTEM; CALCIUM ACTIVITY; GENE WT1 AB Human genetic and in vivo animal studies have helped to define the critical importance of podocytes for kidney function in health and disease. However, as in any other research area, by default these approaches do not allow for mechanistic studies. Such mechanistic studies require the availability of cells grown ex vivo (i. e., in culture) with the ability to directly study mechanistic events and control the environment such that specific hypotheses can be tested. A seminal breakthrough came about a decade ago with the documentation of differentiation in culture of primary rat and human podocytes and the subsequent development of conditionally immortalized differentiated podocyte cell lines that allow deciphering the decisive steps of differentiation and function of `in vivo' podocytes. Although this paper is not intended to provide a comprehensive review of podocyte biology, nor their role in proteinuric renal diseases or progressive glomerulosclerosis, it will focus specifically on several aspects of podocytes in culture. In particular, we will discuss the scientific and research rationale and need for cultured podocytes, how podocyte cell-culture evolved, and how cultured podocytes are currently being used to uncover novel functions of podocytes that can then be validated in vivo in animal or human studies. In addition, we provide a detailed description of how to properly culture and characterize podocytes to avoid potential pitfalls. C1 Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Mundel, P (reprint author), Mt Sinai Sch Med, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM peter.mundel@mssm.edu FU NIDDK NIH HHS [DK57683, DK062472, DK064236, DK073495, DK51096, DK56799, DK60525] NR 100 TC 161 Z9 183 U1 1 U2 12 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 JUL PY 2007 VL 72 IS 1 BP 26 EP 36 DI 10.1038/sj.ki.5002291 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 188HD UT WOS:000247909800006 PM 17457377 ER PT J AU Park, SH Yee, J Kim, SH Kim, YH AF Park, Seong Ho Yee, Judy Kim, Se Hyung Kim, Young Hoon TI Fundamental elements for successful performance of CT Colonography (Virtual colonoscopy) SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE computed tomography (CT); colonography; CTC; virtual colonoscopy; review ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; OPTIMIZING COLONIC DISTENSION; CONTRAST BARIUM ENEMA; AIDED POLYP DETECTION; CONVENTIONAL COLONOSCOPY; CATHARTIC PREPARATION; COLORECTAL NEOPLASIA; ASYMPTOMATIC ADULTS; NATIONAL-SURVEY; SPIRAL CT AB There are many factors affecting the successful performance of CT colonography (CTC). Adequate colonic cleansing and distention, the optimal CT technique and interpretation with using the newest CTC software by a trained reader will help ensure high accuracy for lesion detection. Fecal and fluid tagging may improve the diagnostic accuracy and allow for reduced bowel preparation. Automated carbon dioxide insufflation is more efficient and may be safer for colonic distention as compared to manual room air insufflation. CT scanning should use thin collimation of <= 3 mm with a reconstruction interval of <= 1.5 mm and a low radiation dose. There is not any one correct method for the interpretation of CTC; therefore, readers should be well-versed with both the primary 3D and 2D reviews. Polyps detected at CTC should be measured accurately and reported following the "polyp size-based" patient management system. The time-intensive nature of CTC and the limited resources for training radiologists appear to be the major barriers for implementing CTC in Korea. C1 Univ Ulsan, Coll Med, Dept Radiol, Asan Med Ctr, Seoul 138736, South Korea. Univ Ulsan, Coll Med, Res Inst Radiol, Asan Med Ctr, Seoul 138736, South Korea. Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. Seoul Natl Univ Hosp, Dept Radiol, Seoul 110744, South Korea. Seoul Natl Univ Hosp, Inst Radiat Med, Seoul 110744, South Korea. Seoul Natl Univ, Bundang Hosp, Dept Radiol, Songnam 468802, South Korea. RP Park, SH (reprint author), Univ Ulsan, Coll Med, Dept Radiol, Asan Med Ctr, 388-1 Poongnap-2Dong, Seoul 138736, South Korea. EM seongho@amc.seoul.kr RI Kim, Young Hoon/J-5416-2012; OI Park, Seong Ho/0000-0002-1257-8315 NR 71 TC 21 Z9 21 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JUL-AUG PY 2007 VL 8 IS 4 BP 264 EP 275 DI 10.3348/kjr.2007.8.4.264 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 200TN UT WOS:000248785800001 PM 17673837 ER PT J AU Grosso, F Jones, RL Demetri, GD Judson, IR Blay, JY Le Cesne, A Sanfilippo, R Casieri, P Collini, P Dileo, P Spreafico, C Stacchiotti, S Tamborini, E Tercero, JC Jimeno, J D'Incalci, M Gronchi, A Fletcher, JA Pilotti, S Casali, PG AF Grosso, Federica Jones, Robin L. Demetri, George D. Judson, Ian R. Blay, Jean-Yves Le Cesne, Axel Sanfilippo, Roberta Casieri, Paola Collini, Paola Dileo, Palma Spreafico, Carlo Stacchiotti, Silvia Tamborini, Elena Tercero, Juan Carlos Jimeno, Jose D'Incalci, Maurizio Gronchi, Alessandro Fletcher, Jonathan A. Pilotti, Silvana Casali, Paola G. TI Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study SO LANCET ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMAS; GASTROINTESTINAL STROMAL TUMORS; PHASE-II; EUROPEAN-ORGANIZATION; IMATINIB MESYLATE; SOLID TUMORS; TLS-CHOP; CHEMOTHERAPY; ET-743; COMPOUND AB Background Previous studies have suggested that trabectedin (ecteinascidin-743) could have antitumour activity in soft-tissue sarcoma. We aimed to study the usefulness of trabectedin in the treatment of patients with myxoid liposarcomas, a subtype of liposarcoma that is associated with specific chromosomal translocations t(12;16)(q13;p11) or t(12;22)(q13;q12) that result in the formation of DDIT3-FUS or DDIT3-EWSR1 fusion proteins. Methods 51 patients with advanced pretreated myxoid liposarcoma who started treatment with trabectedin between April 4, 2001, and Sept 18, 2006 at five institutions in a compassionate-use programme were analysed retrospectively. Centralised. radiological and pathological reviews were done for most patients. Trabectedin was given either as a 24-h continuous infusion or as a 3-h infusion, every 21 days, at 1.1-1.5 mg/m(2). 558 courses of trabectedin were given in total, with a median of ten courses for each patient (range 1-23). The primary endpoints were response rate and progression-free survival, and the secondary endpoint was overall survival. Findings According to Response Evaluation Criteria in Solid Tumors (RECIST), after a median follow-up of 14.0 months (IQR 8.7-20.0), two patients had complete responses (CR) and 24 patients had partial responses (PR); the overall response was 51% (95% CI 36-65). Five patients had early progressive disease. In 17 of the 23 patients who achieved PR or CR as defined by RECIST and who had centralised radiological review, tissue-density changes, consisting of a decrease in tumour density on CT scan or a decrease in contrast enhancement on MRI (or both), preceded tumour shrinkage. Median progression-free survival was 14.0 months (13.1-21.0), and progression-free survival at 6 months was 88% (79-95). Interpretation Trabectedin was associated with antitumour activity in this series of patients with myxoid liposarcoma. The noted patterns of tumour response were such that tissue density changes occurred before tumour shrinkage in several patients. In some patients, tissue-density changes only were seen. Long-lasting tumour control was noted in responsive patients. The compassionate-use programme is still ongoing, This analysis has resulted in the initiation of two prospective studies to assess the role of trabectedin in the treatment of patients with myxoid liposarcoma in preoperative and metastatic settings. Furthermore, the selective mechanism of action for trabectedin in this translocation-related sarcoma is being studied. C1 Natl Canc Inst, IRCCS Fdn, Dept Canc Med, Adult Sarcoma Med Treatment Unit, I-20133 Milan, Italy. Royal Marsden Hosp, Dept Med, Sarcoma Unit, London SW3 6JJ, England. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. Ctr Leon Berard, Dept Oncol, F-69373 Lyon, France. Inst Gustave Roussy, Dept Med, Villejuif, France. Natl Canc Inst, IRCCS Fdn, Dept Pathol, I-20133 Milan, Italy. Natl Canc Inst, IRCCS Fdn, Dept Radiol, I-20133 Milan, Italy. PharmaMar Res & Dev, Madrid, Spain. Mario Negri Inst Pharmacol Res, Dept Oncol, I-20157 Milan, Italy. Natl Canc Inst, IRCCS Fdn, Dept Surg, I-20133 Milan, Italy. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Grosso, F (reprint author), Natl Canc Inst, IRCCS Fdn, Dept Canc Med, Adult Sarcoma Med Treatment Unit, Via G Venezian 1, I-20133 Milan, Italy. EM federica.grosso@istitutotumori.mi.it RI Blay, Jean-Yves/N-3966-2016; Stacchiotti, Silvia/C-2017-2017; Tamborini, Elena/C-3307-2017; casali, Paolo Giovanni/D-1524-2017; Sanfilippo, Roberta/E-2123-2017; Collini, Paola/K-7354-2016; OI D'Incalci, Maurizio/0000-0001-8784-1360; Blay, Jean-Yves/0000-0001-7190-120X; Stacchiotti, Silvia/0000-0002-1742-8666; Tamborini, Elena/0000-0002-3819-8687; casali, Paolo Giovanni/0000-0003-4056-8023; Sanfilippo, Roberta/0000-0002-9704-0521; Collini, Paola/0000-0002-6158-210X; Gronchi, Alessandro/0000-0002-4703-3534 NR 31 TC 226 Z9 240 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2007 VL 8 IS 7 BP 595 EP 602 DI 10.1016/S1470-2045(07)70175-4 PG 8 WC Oncology SC Oncology GA 190LY UT WOS:000248061500023 PM 17586092 ER PT J AU Bahmad, F Merchant, SN Nadol, JB Tranebjaerg, L AF Bahmad, Fayez, Jr. Merchant, Saumil N. Nadol, Joseph B. Tranebjaerg, Lisbeth TI Otopathology in Mohr-Tranebjaerg syndrome SO LARYNGOSCOPE LA English DT Article DE temporal bone; histopathology; hereditary hearing loss; Mohr-Tranebjaerg syndrome ID DEAFNESS DYSTONIA SYNDROME; AUDITORY NEUROPATHY; DDP1/TIMM8A-TIMM13 COMPLEX; COCHLEAR IMPLANTATION; MENTAL DEFICIENCY; GENE; MUTATION; HISTOPATHOLOGY; BLINDNESS; CARRIERS AB Background: Mohr-Tranebjgaerg syndrome (MTS) is an X-linked, recessive, syndromic sensorineural hearing loss (HL) characterized by onset of deafness in childhood followed later in adult life by progressive neural degeneration affecting the brain and optic nerves. MTS is caused by mutations in the DDP/TIMM8A gene, which encodes for a 97 amino acid polypeptide; this polypeptide is a translocase of the inner mitochondrial membrane. Objectives: To describe the otologic presentation and temporal bone histopathology in four affected individuals with MTS. Material and Methods: All four subjects belonged to a large, multigenerational Norwegian family and were known to carry a frame shift mutation in the TIMM8A gene. Temporal bones were removed at autopsy and studied by light microscopy. Cytocochleograms were constructed for hair cells, stria vascularis, and cochlear neuronal cells. Vestibular neurons were also counted. Results: All four subjects developed progressive HL in early childhood, becoming profoundly deaf by the age of 10 years. All four developed language, and at least one subject used amplification in early life. Audiometric evaluation in two subjects showed 80- to 100-dB HL by the age of 10 years. The subjects died between the ages of 49 and 67. The otopathology was strikingly similar in that all bones examined showed near-total loss of cochlear neuronal cells and severe loss of vestibular neurons. When compared with age-matched controls, there was 90% to 95% loss of cochlear neurons and 75% to 85% loss of vestibular neurons. Conclusions: We infer that the HL in MTS is likely to be the result of a postnatal and progressive degeneration of cochlear neurons and that MTS constitutes a true auditory neuropathy. Our findings have implications for clinical diagnosis of patients with MTS and management of the HL. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Copenhagen, Panum Inst, Wilhelm Johannsen Ctr Funct Genom, Dept Audiol,Bispebjerg Hosp,Inst Mol & Cellular M, DK-2200 Copenhagen, Denmark. Univ Tromso Hosp, Dept Med Genet, N-9012 Tromso, Norway. RP Merchant, SN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu RI Bahmad Jr, Fayez/H-8420-2013 OI Bahmad Jr, Fayez/0000-0002-1575-7589 FU NIDCD NIH HHS [U24 DC008559-02, 1U24DC008559, U24 DC008559] NR 22 TC 18 Z9 21 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2007 VL 117 IS 7 BP 1202 EP 1208 DI 10.1097/MLG.0b013e3180581944 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 186FE UT WOS:000247763700015 PM 17471106 ER PT J AU Castano, AP Dai, TH Yaroslavsky, I Cohen, R Apruzzese, WA Smotrich, MH Hamblin, MR AF Castano, Ana P. Dai, Tianhong Yaroslavsky, Ilya Cohen, Richard Apruzzese, William A. Smotrich, Michael H. Hamblin, Michael R. TI Low-level laser therapy for zymosan-induced arthritis in rats: Importance of illumination time SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE biostimulation; low-level light therapy; zymosan-induced arthritis; photobiomodulation; cold laser; prostaglandin E2 ID CONTROLLED TRIAL; PHOTOBIOMODULATION; INFLAMMATION; IRRADIATION; PAIN; CYCLOOXYGENASE-2; MECHANISMS; RADIATION; PATHWAY; MICE AB Background: It has been proposed for many years that low-level laser (or light) therapy (LLLT) can ameliorate the pain, swelling, and inflammation associated with various forms of arthritis. Light is thought to be absorbed by mitochondrial chromophores leading to an increase in adenosine triphosphate (ATP), reactive oxygen species and/or cyclic AMP production and consequent gene transcription via activation of transcription factors. However, despite many reports about the positive effects of LLLT in arthritis and in medicine in general, its use remains controversial. For all indications (including arthritis) the optimum optical parameters have been difficult to establish and so far are unknown. Methods: We tested LLLT on rats that had zymosan injected into their knee joints to induce inflammatory arthritis. We compared illumination regimens consisting of a high and low fluence (3 and 30 J/cm 2), delivered at high and low irradiance (5 and 50 mlV/cm(2)) using 8 10-nm laser light daily for 5 days, with the positive control of conventional corticosteroid (dexamethasone) therapy. Results: Illumination with 810-nm laser was highly effective (almost as good as dexamethasone) at reducing swelling and a longer illumination time (10 or 100 minutes compared to 1 minute) was more important in determining effectiveness than either the total fluence delivered or the irradiance. LLLT induced reduction of joint swelling correlated with reduction in the inflammatory marker serum prostaglandin E2 (PGE2). Conclusion: LLLT with 810-nm laser is highly effective in treating inflammatory arthritis in this model. Longer illumination times were more effective than short times regardless of total fluence or irradiance. These data will be of value in designing clinical trials of LLLT for various arthritides. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Palomar Med Technol Inc, Burlington, MA 01803 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-05A1, R01-AI050875, R01-CA/AI838801] NR 33 TC 62 Z9 65 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD JUL PY 2007 VL 39 IS 6 BP 543 EP 550 DI 10.1002/lsm.20516 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 198BL UT WOS:000248601900008 PM 17659584 ER PT J AU Dyer, MA Barr, RS Evins, AE AF Dyer, M. A. Barr, R. S. Evins, A. E. TI Nicotinic and glycinergic medications for disorders of hedonic regulation SO LETTERS IN DRUG DESIGN & DISCOVERY LA English DT Review DE nicotine dependence; drug targets; schizophrenia; anhedonia; nicotinic receptors; glycine site/NMDA receptor ID NMDA-RECEPTOR ANTAGONIST; SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL; BRAIN-STIMULATION REWARD; PLACEBO-CONTROLLED TRIAL; DEFICIT HYPERACTIVITY DISORDER; RAT PREFRONTAL CORTEX; PURSUIT EYE-MOVEMENTS; SMOKING-CESSATION; PARTIAL AGONIST AB The majority of current smokers in the U.S. also have at least one comorbid psychiatric illness. Looking at commons mechanisms of nicotine dependence and psychiatric disorders of hedonic regulation reveals nicotinic acetylcholine receptors and the glycine site on NMDA receptors as potential targets for pharmacological treatment of these disorders. C1 Harvard Univ, Sch Med, Schizophrenia Program, Addict Res Program, Boston, MA USA. Massachusetts Gen Hosp, Schrizophrenia Program, Addict Res Program, Boston, MA USA. RP Evins, AE (reprint author), Freedom Trial Clin, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu NR 186 TC 0 Z9 0 U1 2 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 1570-1808 J9 LETT DRUG DES DISCOV JI Lett. Drug Des. Discov. PD JUL PY 2007 VL 4 IS 5 BP 373 EP 381 DI 10.2174/157018007780867852 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 177MU UT WOS:000247158000010 ER PT J AU Court, LE Allen, A Tishler, R AF Court, Laurence E. Allen, Aaron Tishler, Roy TI Evaluation of the precision of portal-image-guided head-and-neck localization: An intra- and interobserver study SO MEDICAL PHYSICS LA English DT Article DE image-guided; localization; setup uncertainty; head and neck; IMRT ID INTENSITY-MODULATED RADIOTHERAPY; SET-UP ERRORS; 3-DIMENSIONAL ULTRASOUND; THERMOPLASTIC MASKS; PATIENT MOTION; ACCURACY; CANCER; IMMOBILIZATION; UNCERTAINTIES; VARIABILITY AB There is increasing evidence that, for some patients, image-guided intensity-modulated radiation therapy (IMRT) for head-and-neck cancer patients may maintain target dose coverage and critical organ (e.g., parotids) dose closer to the planned doses than setup using lasers alone. We investigated inter- and intraobserver uncertainties in patient setup in head-and-neck cancer patients. Twenty-two sets of orthogonal digital portal images (from five patients) were selected from images used for daily localization of head-and-neck patients treated with IMRT. To evaluate interobserver variations, five radiation therapists compared the portal images with the plan digitally reconstructed radiographs and reported shifts for the isocenter (similar to C2) and for a supraclavicular reference point. One therapist repeated the procedure a month later to evaluate intraobserver variations. The procedure was then repeated with teams of two therapists. The frequencies for which agreement between the shift reported by the observer and the daily mean shift (average of all observers for a given image set) were less than 1.5 and 2.5 mm were calculated. Standard errors of measurement for the intra- and interobserver uncertainty (SEMintra and SEMinter) for the individual and teams were calculated. The data showed that there was very little difference between individual therapists and teams. At isocenter, 80%-90% of all reported shifts agreed with the daily average within 1.5 mm, showing consistency in the ways both individuals and teams interpret the images (SEMinter similar to 1 mm). This dropped to 65% for the supraclavicular point (SEMinter similar to 1.5 mm). Uncertainties increased for larger setup errors. In conclusion, image-guided patient positioning allows head-and-neck patients to be controlled within 3-4 mm. This is similar to the setup uncertainties found for most head-and-neck patients, but may provide some improvement for the subset of patients with larger setup uncertainties. (C) 2007 American Association of Physicists in Medicine. C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Court, LE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM lcourt@lroc.harvard.edu NR 28 TC 6 Z9 6 U1 0 U2 1 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 JUL PY 2007 VL 34 IS 7 BP 2704 EP 2707 DI 10.1118/1.2747050 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 191TK UT WOS:000248154700005 PM 17821978 ER PT J AU Seco, J Evans, PM AF Seco, Joao Evans, Phil M. TI Assessing the effect of electron density in photon dose calculations (vol 33, pg 540, 2006) SO MEDICAL PHYSICS LA English DT Correction C1 Harvard Med Sch, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. Royal Marsden NHS Fdn Trust, Inst Canc Res, Joint Dept Phys, Sutton SM2 5PT, Surrey, England. RP Seco, J (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012 NR 3 TC 0 Z9 0 U1 0 U2 3 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 JUL PY 2007 VL 34 IS 7 BP 3121 EP 3121 DI 10.1118/1.2739809 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 191TK UT WOS:000248154700047 ER PT J AU Schneider, A Schwarz, TF Hammerschmidt, T Siebert, U AF Schneider, Achim Schwarz, Tino F. Hammerschmidt, Thomas Siebert, Uwe TI Impact of vaccination against oncogenic human papillomavirus on the incidence and mortality of cervical cancer in germany SO MEDIZINISCHE KLINIK LA German DT Article DE cervical cancer; incidence; mortality; vaccination; human papillomavirus ID PARTICLE VACCINE; YOUNG-WOMEN; WORLDWIDE; EPIDEMIOLOGY; INFECTION; NEOPLASIA; PROGRAMS; EFFICACY; TYPE-18; TRIAL AB Background and Purpose: Human papillomavirus (HPV) is a necessary cause for cervical cancer. HPV vaccines covering genotypes 16 and 18 for the prevention of cervical cancer are or will be available soon (status: May 2007). Vaccination against HPV in order to reduce the burden of cervical cancer is recommended by the Standing Committee on Vaccination (STIKO) for female adolescents aged 12-17 years in Germany. The study aims to evaluate the achievable long-term impact of HPV vaccination on invasive cervical cancer (ICC) incidence and mortality in Germany, a country with an opportunistic Pap screening program and suboptimal participation. Methods: The authors developed a decision-analytic discrete-event model and used Monte Carlo simulation to assess the impact of vaccination on ICC incidence and life expectancy of a cohort of 399,400 10-year-old girls. HPV-16 and HPV-18 account for 73.5% of cancers. In the model, a 100% vaccination rate between 10 and 25 years, and a vaccine efficacy of 95.1% were assumed. Results: Without vaccination, 4,563 ICC cases occur in the cohort (cumulative lifetime incidence: 1.14%), 1,376 women will die from ICC (fatality: 30.2%). Vaccination at age 10 can reduce incidence and mortality by 70% resulting in a gain of 17,819 life-years. 416 girls have to be vaccinated to prevent one death from ICC. Delaying vaccination to women aged 25 years still leads to a 50% reduction of deaths. Conclusion: Despite cytological screening, a high disease burden of cervical cancer remains in Germany. Vaccination in early adolescence can drastically reduce the disease burden. Vaccination of adult women still offers significant benefits. Therefore, HPV vaccination should be added to existing cancer prevention strategies. C1 Charite Univ Med Berlin, Klin Gynakol & Gynakol Onkol, D-12200 Berlin, Germany. Stiftung Juliusspital, Zentrallabor, Wurzburg, Germany. GlaxoSmithKline GmbH & Co KG, Corp Affairs & Business Support, Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. RP Schneider, A (reprint author), Charite Univ Med Berlin, Klin Gynakol & Gynakol Onkol, Campus Benjamin Franklin Hindenburgdamm 30, D-12200 Berlin, Germany. EM achim.schneider@charite.de NR 30 TC 5 Z9 5 U1 0 U2 1 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0723-5003 J9 MED KLIN JI Med. Klin. PD JUL PY 2007 VL 102 IS 7 BP 515 EP 523 DI 10.1007/s00063-007-1065-9 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 192AD UT WOS:000248172200002 PM 17634869 ER PT J AU Pru, JK AF Pru, James K. TI Directly comparing routes of administration and types of hormone therapy on risk markers for breast cancer SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID HEALTHY POSTMENOPAUSAL WOMEN; ESTROGEN PLUS PROGESTIN; TRIAL C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Pru, JK (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL-AUG PY 2007 VL 14 IS 4 BP 611 EP 611 DI 10.1097/gme.0b013e31806010c0 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 189EW UT WOS:000247973200004 PM 17471109 ER PT J AU Shimazaki, K Wadehra, M Forbes, A Chan, AM Goodglick, L Kelly, KA Braun, J Gordon, LK AF Shimazaki, Kaori Wadehra, Madhuri Forbes, Ashley Chan, Ann M. Goodglick, Lee Kelly, Kathleen A. Braun, Jonathan Gordon, Lynn K. TI Epithelial membrane protein 2 modulates infectivity of Chlamydia muridarum (MoPn) SO MICROBES AND INFECTION LA English DT Article DE Chlamydia; epithelial membrane protein-2; infection; host-pathogen interaction ID EPITHELIAL MEMBRANE PROTEIN-2; SURFACE EXPRESSION; HEPARAN-SULFATE; TRACHOMATIS; CELLS; PNEUMONIAE; ATTACHMENT; RECEPTOR; MOUSE AB Chlamydiae are bacterial pathogens which have evolved efficient strategies to enter, replicate, and survive inside host epithelial cells, resulting in acute and chronic diseases in humans and other animals. Several candidate molecules in the host receptor complex have been identified, but the precise mechanisms of infection have not been elucidated. Epithelial membrane protein-2 (EMP2), a 4-transmembrane protein, is highly expressed in epithelial cells in sites of chlamydial infections. Here we show that infectivity of the Chlamydia muridarum (MoPn) is associated with host cellular expression of EMP2 in multiple cell lines. Recombinant knockdown of EMP2 impairs infectivity, whereas infectivity is augmented in cells recombinantly modified to over-express EMP2. An epithelial cell line without native expression of EMP2 is relatively resistant to MoPn infection, whereas infectivity is markedly increased by recombinant expression of EMP2 in that cell line. Blockade of surface EMP2 using a specific anti-EMP2 antibody significantly reduces chlamydial infection efficiency. In addition, MoPn infectivity as measured in the EMP2 overexpressing cell line is not heparin-dependent, suggesting a possible role for EMP2 in the non-reversible phase of early infection. These findings identify EMP2 as a candidate host protein involved in infection of C. muridarum (MoPn). (c) 2007 Elsevier Masson SAS. All rights reserved. C1 Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Dept Pathol & Lab, Los Angeles, CA 90095 USA. Dept Physiol Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA 90099 USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU NCI NIH HHS [CA009120, P30 CA016042, CA016042]; NIAID NIH HHS [R01 AI026328, 2-T32-AI-07323, AI26328]; NICHD NIH HHS [HD48540, R03 HD048540]; NIGMS NIH HHS [GM007185] NR 27 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2007 VL 9 IS 8 BP 1003 EP 1010 DI 10.1016/j.micinf.2007.04.004 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 197CN UT WOS:000248531300012 PM 17544801 ER PT J AU Prunier, AL Schuch, R Fernandez, RE Mumy, KL Kohler, H McCormick, BA Maurelli, AT AF Prunier, Anne-Laure Schuch, Raymond Fernandez, Reinaldo E. Mumy, Karen L. Kohler, Henrik McCormick, Beth A. Maurelli, Anthony T. TI nadA and nadB of Shigella flexneri 5a are antivirulence loci responsible for the synthesis of quinolinate, a small molecule inhibitor of Shigella pathogenicity SO MICROBIOLOGY-SGM LA English DT Article ID ESCHERICHIA-COLI; BACTERIAL PATHOGENS; III SECRETION; PATHOADAPTIVE MUTATIONS; SALMONELLA-TYPHIMURIUM; INTESTINAL EPITHELIUM; INVASION GENES; BLACK-HOLES; PLASMID; VIRULENCE AB The evolution of bacterial pathogens from commensal organisms involves virulence gene acquisition followed by pathoadaptation to the new host, including inactivation of antivirulence loci (AVL). AVL are core ancestral genes whose expression is incompatible with the pathogenic lifestyle. Previous studies identified cadA (encoding lysine decarboxylase) as an AVL of Shigella spp. In this study, AVL of Shigella were identified by examining a phenotypic difference from its non-pathogenic ancestor, Escherichia coli. Unlike most E. coli strains, Shigella sop. are nicotinic acid auxotrophs, the pathway for the de novo synthesis of NAD being uniformly defective. In Shigella flexneri, this defect is due to alterations in the nadA and/or nadB genes encoding the enzyme complex that converts L-aspartate to quinolinate, a precursor to NAD synthesis. Quinolinate was found to inhibit invasion and cell-to-cell spread of Sh. flexneri 5a and its ability to induce polymorphonuclear neutrophil transepithelial migration. Virulence of other Shigella species was also inhibited by quinolinate. Introduction of functional nadA and nadB genes from E coli K-12 into Sh. flexneri 5a restored its ability to synthesize quinolinate but also resulted in strong attenuation of virulence in this strain. The results define nadA and nadB as AVL in Shigella and validate the concept of pathoadaptive evolution of bacteria from commensal ancestors by inactivation of AVL. They also suggest that studies focusing on this form of bacterial evolution can identify novel inhibitors of virulence in other bacterial pathogens. C1 Univ Klinikum Erlangen, Fredrich Alexander Univ, D-91054 Erlangen, Germany. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Maurelli, AT (reprint author), Rockefeller Univ, Lab Bacterial Pathogenesis & Immunol, 1230 York Ave, New York, NY 10021 USA. EM amaurelli@usuhs.mil FU NIAID NIH HHS [AI061058, AI24656]; NIDDK NIH HHS [DK33506, DK56754] NR 40 TC 36 Z9 36 U1 0 U2 8 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUL PY 2007 VL 153 BP 2363 EP 2372 DI 10.1099/mic.0.2007/006916-0 PN 7 PG 10 WC Microbiology SC Microbiology GA 191TM UT WOS:000248154900036 PM 17600080 ER PT J AU Wang, J Sun, HQ Macia, E Kirchhausen, T Watson, H Bonifacino, JS Yin, HL AF Wang, Jing Sun, Hui-Qiao Macia, Eric Kirchhausen, Tomas Watson, Hadiya Bonifacino, Juan S. Yin, Helen L. TI PIP promotes the recruitment of the GGA adaptor proteins to the trans-Golgi TS recognition of the ubiquitin network and regulates their sorting signal SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; FACTOR-BINDING PROTEINS; AMINO-TERMINAL DOMAIN; SACCHAROMYCES-CEREVISIAE; MOLECULAR-MECHANISM; GAT DOMAIN; MEMBRANE; CLATHRIN; ARF; TRAFFICKING AB Phosphatidylinositol 4 phosphate (PI4P) is highly enriched in the trans-Golgi network (TGN). Here we establish that PI4P is a key regulator of the recruitment of the GGA clathrin adaptor proteins to the TGN and that PI4P has a novel role in promoting their recognition of the ubiquitin (Ub) sorting signal. Knockdown of PI4KII alpha by RNA interference (RNAi), which depletes the TGN's PI4P, impaired the recruitment of the GGAs to the TGN. GGAs bind PI4P primarily through their GAT domain, in a region called C-GAT, which also binds Ub but not Arf1. We identified two basic residues in the GAT domain that are essential for PI4P binding in vitro and for the recruitment of GGAs to the TGN in vivo. Unlike wild-type GGA, GGA with mutated GATs failed to rescue the abnormal TGN phenotype of the GGA RNAi-depleted cells. These residues partially overlap with those that bind Ub, and PI4P increased the affinity of the GAT domain for Ub. Because the recruitment of clathrin adaptors and their cargoes to the TGN is mediated through a web of low-affinity interactions, our results show that the dual roles of PI4P can promote specific GGA targeting and cargo recognition at the TGN. C1 Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res Inst Biomed Res, Boston, MA 02115 USA. Natl Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Yin, HL (reprint author), Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. EM Yin@UTSouthwestern.edu FU NIGMS NIH HHS [GM055562, GM36548, R01 GM036548, R01 GM055562] NR 40 TC 84 Z9 86 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2007 VL 18 IS 7 BP 2646 EP 2655 DI 10.1091/mbc.E06-10-0897 PG 10 WC Cell Biology SC Cell Biology GA 183WV UT WOS:000247604000025 PM 17494868 ER PT J AU Weisberg, E Kung, AL Wright, RD Moreno, D Catley, L Ray, A Zawel, L Tran, M Cools, J Gilliland, G Mitsiades, C McMillin, DW Jiang, JR Hall-Meyers, E Griffin, JD AF Weisberg, Ellen Kung, Andrew L. Wright, Renee D. Moreno, Daisy Catley, Laurie Ray, Arghya Zawel, Leigh Tran, Mary Cools, Jan Gilliland, Gary Mitsiades, Constantine McMillin, Douglas W. Jiang, Jingrui Hall-Meyers, Elizabeth Griffin, James D. TI Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID INTERNAL TANDEM DUPLICATION; ACUTE MYELOID-LEUKEMIA; X-LINKED INHIBITOR; TYROSINE KINASE; FLT3 GENE; SURVIVIN EXPRESSION; ACTIVATING MUTATION; APOPTOSIS PROTEINS; THERAPEUTIC TARGET; DROSOPHILA-REAPER AB Members of the inhibitor of apoptosis protein (IAP) family play a role in mediating apoptosis. Studies suggest that these proteins may be a viable target in leukemia because they have been found to be variably expressed in acute leukemias and are associated with chemosensitivity, chemoresistance, disease progression, remission, and patient survival. Another promising therapeutic target, FLT3, is mutated in about one third of acute myelogenous leukemia (AML) patients; promising results have recently been achieved in clinical trials investigating the effects of the protein tyrosine kinase inhibitor PKC412 on AML patients harboring mutations in the FLT3 protein. Of growing concern, however, is the development of drug resistance resulting from the emergence of point mutations in targeted tyrosine kinases used for treatment of acute leukemia patients. One approach to overriding resistance is to combine structurally unrelated inhibitors and/or inhibitors of different signaling pathways. The proapoptotic IAP inhibitor, LBW242, was shown in proliferation studies done in vitro to enhance the killing of PKC412-sensitive and PKC412-resistant cell lines expressing mutant FLT3 when combined with either PKC412 or standard cytotoxic agents (doxorubicin and Ara-c). In addition, in an in vivo imaging assay using bioluminescence as a measure of tumor burden, a total of 12 male NCr-nude mice were treated for 10 days with p.o. administration of vehicle, LBW242 (50 mg/kg/day), PKC412 (40 mg/kg/day), or a combination of LBW242 and PKC412; the lowest tumor burden was observed in the drug combination group. Finally, the combination of LBW242 and PKC412 was sufficient to override stromal-mediated viability signaling conferring resistance to PKC412. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Novartis Inst Biomed Res, Cambridge, MA USA. Mater Hlth Serv, Brisbane, Qld, Australia. Univ Leuven, Dept Mol & Dev Genet, Flanders Interuniv Inst Biotechnol VIB, Louvain, Belgium. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM James_Griffin@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; OI Cools, Jan/0000-0001-6626-5843; Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA36167, CA66996]; NIDDK NIH HHS [DK50654] NR 48 TC 49 Z9 51 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2007 VL 6 IS 7 BP 1951 EP 1961 DI 10.1158/1535-7163.MCT-06-0810 PG 11 WC Oncology SC Oncology GA 191TG UT WOS:000248154300005 PM 17620426 ER PT J AU Singh, S Shi, Q Bailey, ST Palczewski, MJ Pardee, AB Iglehart, JD Biswas, DK AF Singh, Sindhu Shi, Qian Bailey, Shannon T. Palczewski, Marek J. Pardee, Arthur B. Iglehart, J. Dirk Biswas, Debajit K. TI Nuclear factor-kappa B activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CELL-CYCLE PROGRESSION; BASAL-LIKE SUBTYPE; IKK-ALPHA; CARCINOMA; PATHWAY; INHIBITION; EXPRESSION; APOPTOSIS; PROTEINS; OVEREXPRESSION AB Nuclear factor-kappa B (NF-kappa B), a transcription factor with pleotropic effects, is a downstream mediator of growth signaling in estrogen receptor (ER)-negative and erbB family particularly erbB2 (HER-2/neu) receptor-positive cancer. We previously reported activation of NF-kappa B in ER-negative breast cancer cells and breast tumor specimens, but the consequence of inhibiting NF-kappa B activation in this subclass of breast cancer has not been shown. In this study, we investigated the role of NF-kappa B activation by studying the tumorigenic potential of cells expressing genetically manipulated, inducible, dominant-negative inhibitory kappa B kinase (IKK) beta in xenograft tumor model. Conditional inhibition of NF-kappa B activation by the inducible expression of dominant-negative IKK beta simultaneously blocked cell proliferation, reinstated apoptosis, and dramatically blocked xenograft tumor formation. Secondly, the humanized anti-erbB2 antibody trastuzumab (Herceptin) and the specific IKK inhibitor NF-kappa B essential modifier-binding domain peptide both blocked NF-kappa B activation and cell proliferation and reinstated apoptosis in two ER-negative and erbB2-positive human breast cancer cell lines that are used as representative model systems.Combinations of these two target-specific inhibitors synergistically blocked cell proliferation at concentrations that were singly ineffective. Inhibition of NF-kappa B activation with two other low molecular weight compounds, PS1145 and PS341, which inhibited IKK activity and proteasome-mediated phosphorylated inhibitory kappa B protein degradation, respectively, blocked erbB2-mediated cell growth and reversed antiapoptotic machinery. These results implicate NF-kappa B activation in the tumorigenesis and progression of ER-negative breast cancer. It is postulated that this transcription factor and its activation cascade offer therapeutic targets for erbB2-positive and ER-negative breast cancer. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Smith Room 1058,44 Binney St, Boston, MA 02115 USA. EM Debajit_Biswas@dfci.harvard.edu RI Bailey, Shannon/B-8045-2014 NR 42 TC 56 Z9 60 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2007 VL 6 IS 7 BP 1973 EP 1982 DI 10.1158/1535-7163.MCT-07-0063 PG 10 WC Oncology SC Oncology GA 191TG UT WOS:000248154300007 PM 17620428 ER PT J AU Tam, JM Upadhyay, R Pittet, MJ Weissleder, R Mahmood, U AF Tam, Jenny M. Upadhyay, Rabi Pittet, Mikacl J. Weissleder, Ralph Mahmood, Umar TI Improved in vivo whole-animal detection limits of green fluorescent protein-expressing tumor lines by spectral fluorescence imaging SO MOLECULAR IMAGING LA English DT Article ID GENE-EXPRESSION; CANCER; PROBES; MICE; ANGIOGENESIS; FEASIBILITY; METASTASIS AB Green fluorescent protein (GFP) has been used for cell tracking and imaging gene expression in superficial or surgically exposed structures. However, in vivo murine imaging is often limited by several factors, including scatter and attenuation with depth and overlapping autofluorescence. The autofluorescence signals have spectral profiles that are markedly different from the GFP emission spectral profile. The use of spectral imaging allows separation and quantitation of these contributions to the total fluorescence signal seen in vivo by weighting known pure component profiles. Separation of relative GFP and autofluorescence signals is not readily possible using epifluorescent continuous-wave single excitation and emission bandpass imaging (EFI). To evaluate detection thresholds using these two methods, nude mice were subcutaneously injected with a series of GFP-expressing cells. For EFI, optimized excitation and emission bandpass filters were used. Owing to the ability to separate autofluorescence contributions from the emission signal using spectral imaging compared with the mixed contributions of GFP and autofluorescence in the emission signal recorded by the EFI system, we achieved a 300-fold improvement in the cellular detection limit. The detection limit was 3 x 10(3) cells for spectral imaging versus 1 X 10(6) cells for EFI. Despite contributions to image stacks from autofluorescence, a 100-fold dynamic range of cell number in the same image was readily visualized. Finally, spectral imaging was able to separate signal interference of red fluorescent protein from GFP images and vice versa. These findings demonstrate the utility of the approach in detecting low levels of multiple fluorescent markers for whole-animal in vivo applications. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Simches 8226,185 Cambridge St, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [P50-CA86355, R24-CA92782]; NIBIB NIH HHS [R01-EB001872] NR 16 TC 22 Z9 23 U1 1 U2 3 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD JUL-AUG PY 2007 VL 6 IS 4 BP 269 EP 276 DI 10.2310/7290.2007.00023 PG 8 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 208WE UT WOS:000249349100006 PM 17711782 ER PT J AU Funke, BH Lencz, T Finn, CT DeRosse, P Poznik, GD Plocik, AM Kane, J Rogus, J Malhotra, AK Kucherlapati, R AF Funke, Birgit H. Lencz, Todd Finn, Christine T. DeRosse, Pamela Poznik, G. David Plocik, Alex M. Kane, John Rogus, John Malhotra, Anil K. Kucherlapati, Raju TI Analysis of TBX1 variation in patients with psychotic and affective disorders SO MOLECULAR MEDICINE LA English DT Article ID 22Q11 DELETION SYNDROME; CARDIO-FACIAL SYNDROME; OBSESSIVE-COMPULSIVE DISORDER; PREPULSE INHIBITION; NO ASSOCIATION; SPECTRUM DISORDERS; CHINESE POPULATION; TOURETTES-SYNDROME; GENETIC-VARIATION; SYNDROME REGION AB A significant portion of patients with 22q11 deletion syndrome (22q11 DS) develop psychiatric disorders, including schizophrenia and other psychotic and affective symptoms, and the responsible gene/s are assumed to also play a significant role in the etiology of nonsyndromic psychiatric disease. The most common psychiatric diagnosis among patients with 22q 11DS is schizophrenia, thought to result from neurotransmitter imbalances and also from disturbed brain development. Several genes in the 22q 11 region with known or suspected roles in neurotransmitter metabolism have been analyzed in patients with isolated schizophrenia; however, their contribution to the disease remains controversial, Haploinsufficiency of the TBX1 gene has been shown to be sufficient to cause the core physical malformations associated with 22q 11 DS in mice and humans and via abnormal brain development could contribute to 22q 11 DS-related and isolated psychiatric disease. 22q 11DS populations also have increased rates of psychiatric conditions other than schizophrenia, including mood disorders. We therefore analyzed variations at the TBX1 locus in a cohort of 446 white patients with psychiatric disorders relevant to 22q 11 DS and 436 ethnically matched controls, The main diagnoses included schizophrenia (n = 226), schizoaffective disorder (n = 67), bipolar disorder (n = 82), and major depressive disorder (n = 29). We genotyped nine tag SNPs in this sample but did not observe significant differences in allele or haplotype frequencies in any of the analyzed groups (all affected, schizophrenia and schizoaffective disorder, schizophrenia alone, and bipolar disorder and major depressive disorder) compared with the control group. Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q 11 DS. C1 Harvard Partners Ctr Genet & Genom, Mol Med Lab, Cambridge, MA 02139 USA. Zucker Hillside Hosp, Glen Oaks, NY USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Funke, BH (reprint author), Harvard Partners Ctr Genet & Genom, Mol Med Lab, 65 Landsdowne St, Cambridge, MA 02139 USA. EM bfunke@partners.org RI Lencz, Todd/J-3418-2014; OI Lencz, Todd/0000-0001-8586-338X; Plocik, Alex/0000-0001-9489-6466 FU NCRR NIH HHS [M01 RR018535, M01 RR18535]; NICHD NIH HHS [HD034980-09]; NIMH NIH HHS [K01 MH065580, K01 MH65580, K23 MH001760, K23MH001760, P30 MH060575, P30 MH60575] NR 74 TC 7 Z9 7 U1 0 U2 0 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL-AUG PY 2007 VL 13 IS 7-8 BP 407 EP 414 DI 10.2119/2006-00119.Funke PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 204NF UT WOS:000249050300013 PM 17622328 ER PT J AU Brousseau, KM Arciniegas, DB Carmosino, MJ Corboy, JR AF Brousseau, K. M. Arciniegas, D. B. Carmosino, M. J. Corboy, J. R. TI The differential diagnosis of Axis I psychopathology presenting to a university-based multiple sclerosis clinic SO MULTIPLE SCLEROSIS LA English DT Article DE differential diagnosis; multiple sclerosis; psychophysiological disorders; neurobehavioral manifestations; somatoform disorders; examinations AB Patients carrying a presumptive diagnosis of multiple sclerosis (MS) sometimes present with nonspecific clinical signs and symptoms that may be, at least in part, somatic manifestations of psychiatric conditions. This retrospective study was undertaken to identify psychiatric diagnoses among 63 patients whose initial clinical evaluations suggested a primary psychiatric, rather than a primary neurological, etiology for their symptoms. Some 92% of patients met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) criteria for one or more primary psychiatric disorders, most often including somatoform, mood, and anxiety disorders. Accurate identification and diagnosis of psychiatric conditions producing pseudo neurological or non-specific somatic symptoms is necessary for both treatment and medico-economic reasons. C1 Univ Colorado, Sch Med, Dept Med,Dept Psychiat,Div Infect Dis, VISN 19 MIRECC,Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Sch Med, Dept Psychiat, Neuropsychiat Serv, Denver, CO USA. Univ Colorado, Sch Med, Univ Colorado Multiple Sclerosis Ctr, Dept Neurol, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. RP Brousseau, KM (reprint author), Univ Colorado, Sch Med, Dept Med,Dept Psychiat,Div Infect Dis, VISN 19 MIRECC,Vet Affairs Med Ctr, Denver, CO 80220 USA. EM kristin.brousseau@uchsc.edu RI Arciniegas, David/A-3792-2009 NR 8 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD JUL PY 2007 VL 13 IS 6 BP 749 EP 753 DI 10.1177/1352458506075032 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 193JK UT WOS:000248270100009 PM 17613603 ER PT J AU Kim, DY Carey, BW Wang, HB Ingano, LAM Binshtok, AM Wertz, MH Pettingell, WH He, P Lee, VMY Woolf, CJ Kovacs, DM AF Kim, Doo Yeon Carey, Bryce W. Wang, Haibin Ingano, Laura A. M. Binshtok, Alexander M. Wertz, Mary H. Pettingell, Warren H. He, Ping Lee, Virginia M. -Y. Woolf, Clifford J. Kovacs, Dora M. TI BACE1 regulates voltage-gated sodium channels and neuronal activity SO NATURE CELL BIOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE BACE1; ALZHEIMERS-DISEASE; ALPHA-SUBUNIT; CELL-ADHESION; MOLECULAR-MECHANISMS; MESSENGER-RNAS; RAT-BRAIN; IN-VIVO; SEIZURES AB BACE1 activity is significantly increased in the brains of Alzheimer's disease patients, potentially contributing to neurodegeneration. The voltage-gated sodium channel ( Na(v)1) beta 2-subunit (beta 2), a type I membrane protein that covalently binds to Nav1 alpha-subunits, is a substrate for BACE1 and gamma-secretase. Here, we find that BACE1-gamma-secretase cleavages release the intracellular domain of beta 2, which increases mRNA and protein levels of the pore-forming Na v 1.1 a-subunit in neuroblastoma cells. Similarly, endogenous beta 2 processing and Na(v) 1.1 protein levels are elevated in brains of BACE1-transgenic mice and Alzheimer's disease patients with high BACE1 levels. However, Na(v) 1.1 is retained inside the cells and cell surface expression of the Na(v) 1 alpha-subunits and sodium current densities are markedly reduced in both neuroblastoma cells and adult hippocampal neurons from BACE1-transgenic mice. BACE1, by cleaving beta 2, thus regulates Na(v)1 alpha-subunit levels and controls cell-surface sodium current densities. BACE1 inhibitors may normalize membrane excitability in Alzheimer's disease patients with elevated BACE1 activity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Neurobiol Dis Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plastic Res Grp, Boston, MA 02129 USA. Sun Hlth Res Inst, Haldeman Lab Mol & Cellular Neurobiol, Sun City, AZ 85351 USA. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Kovacs, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Neurobiol Dis Lab, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu FU NIA NIH HHS [P01 AG015379, P01 AG015379-100006, R01 AG014713, R01 AG014713-11] NR 44 TC 149 Z9 151 U1 2 U2 13 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 JUL PY 2007 VL 9 IS 7 BP 755 EP U43 DI 10.1038/ncb1602 PG 16 WC Cell Biology SC Cell Biology GA 186EA UT WOS:000247760700011 PM 17576410 ER PT J AU Khalid, A AF Khalid, Asif TI Do all patients with pancreatic cysts need to undergo resection or can some be monitored? SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE nonoperative management; operative management; pancreatic cysts; patient selection C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, GI Sect, Pittsburgh, PA USA. RP Khalid, A (reprint author), Presbyterian Univ Hosp, M2,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD JUL PY 2007 VL 4 IS 7 BP 368 EP 369 DI 10.1038/ncpgasthep0840 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 185PD UT WOS:000247722000006 PM 17502883 ER PT J AU Munshi, NC Mitsiades, CS Richardson, PG Anderson, KC AF Munshi, Nikhil C. Mitsiades, Constantine S. Richardson, Paul G. Anderson, Kenneth C. TI Does maintenance therapy with thalidomide benefit patients with multiple myeloma? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE chromosome 13; maintenance therapy; myeloma; thalidomide ID IMPROVES SURVIVAL C1 Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, JLMMC, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol Neoplasia, DFCI, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston VA Healthcare Syst, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, JLMMC, 44 Binney St,Mayer 557, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUL PY 2007 VL 4 IS 7 BP 394 EP 395 DI 10.1038/ncponc0847 PG 2 WC Oncology SC Oncology GA 183QX UT WOS:000247588400005 PM 17534287 ER PT J AU Chen, WY Colditz, GA AF Chen, Wendy Y. Colditz, Graham A. TI Risk factors and hormone-receptor status: epidemiology, risk-prediction models and treatment implications for breast cancer SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE breast cancer; epidemiology; hormone receptor; risk models ID ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; GENE-EXPRESSION PROFILES; BODY-MASS INDEX; REPLACEMENT THERAPY; ALCOHOL-CONSUMPTION; PROSPECTIVE COHORT; PROGNOSTIC CHARACTERISTICS; COLLABORATIVE REANALYSIS; REPRODUCTIVE FACTORS AB It is increasingly being recognized that breast cancer does not represent a single homogeneous disease; instead, the hormone-receptor status defines important clinical and etiologic differences. We review the epidemiologic data on differences in risk-factor associations by hormone-receptor status and highlight major trends in the literature. We discuss the development and evaluation of breast cancer risk models, with a focus on the Rosner and Colditz model, which can separately estimate the risk of hormone-receptor-positive and hormone-receptor-negative breast cancers. We also discuss the clinical implications of accounting for hormone-receptor status in breast cancer risk-prediction models. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, WA USA. RP Chen, WY (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM wendy.chen@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 78 TC 49 Z9 49 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUL PY 2007 VL 4 IS 7 BP 415 EP 423 DI 10.1038/ncponc0851 PG 9 WC Oncology SC Oncology GA 183QX UT WOS:000247588400011 PM 17597706 ER PT J AU Altshuler, D Daly, M AF Altshuler, David Daly, Mark TI Guilt beyond a reasonable doubt SO NATURE GENETICS LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; VARIANTS; MULTIPLE; IL23R; LOCI; GENE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Boston, MA 02115 USA. MIT, Broad Inst, Boston, MA USA. RP Altshuler, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM altshuler@molbio.mgh.harvard.edu; mjdaly@chgr.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 15 TC 108 Z9 111 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2007 VL 39 IS 7 BP 813 EP 815 DI 10.1038/ng0707-813 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 184CX UT WOS:000247619800004 PM 17597768 ER PT J AU McCarroll, SA Altshuler, DM AF McCarroll, Steven A. Altshuler, David M. TI Copy-number variation and association studies of human disease SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; LINKAGE DISEQUILIBRIUM; SEGMENTAL DUPLICATIONS; STRUCTURAL VARIANTS; GENETIC ASSOCIATION; LARGE-SCALE; POLYMORPHISM; SUSCEPTIBILITY; NUCLEOTIDE; MAP AB The central goal of human genetics is to understand the inherited basis of human variation in phenotypes, elucidating human physiology, evolution and disease. Rare mutations have been found underlying two thousand mendelian diseases; more recently, it has become possible to assess systematically the contribution of common SNPs to complex disease. The known role of copy-number alterations in sporadic genomic disorders, combined with emerging information about inherited copy-number variation, indicate the importance of systematically assessing copy-number variants (CNVs), including common copy-number polymorphisms (CNPs), in disease. Here we discuss evidence that CNVs affect phenotypes, directions for basic knowledge to support clinical study of CNVs, the challenge of genotyping CNPs in clinical cohorts, the use of SNPs as markers for CNPs and statistical challenges in testing CNVs for association with disease. Critical needs are high-resolution maps of common CNPs and techniques that accurately determine the allelic state of affected individuals. C1 [McCarroll, Steven A.; Altshuler, David M.] Harvard Univ, MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [McCarroll, Steven A.; Altshuler, David M.] Harvard Univ, Cambridge, MA 02138 USA. [McCarroll, Steven A.; Altshuler, David M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Altshuler, David M.] Harvard Univ, Dept Genet & Med, Boston, MA 02115 USA. RP McCarroll, SA (reprint author), Harvard Univ, MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. EM smccarro@broad.mit.edu RI McCarroll, Steven/A-8433-2009; Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; McCarroll, Steven/0000-0002-6954-8184 NR 42 TC 314 Z9 336 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2007 VL 39 SU 7 BP S37 EP S42 DI 10.1038/ng2080 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 274AO UT WOS:000253974400007 PM 17597780 ER PT J AU Schmidt-Supprian, M Rajewsky, K AF Schmidt-Supprian, Marc Rajewsky, Klaus TI Vagaries of conditional gene targeting SO NATURE IMMUNOLOGY LA English DT Editorial Material ID CRE RECOMBINASE; CELL-DEVELOPMENT; MAMMALIAN-CELLS; TRANSGENIC MICE; B-LYMPHOCYTES; TOXICITY; MAINTENANCE; EXPRESSION; GENOMES AB Conditional gene targeting based on excision or inversion of loxP-flanked DNA segments by Cre recombinase is a powerful technology for the analysis of gene function, but unexpected expression patterns of cre transgenes, variability of recombination efficiency depending on the target gene and potential toxicity of Cre recombinase represent serious challenges for the experimenter. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR, Inst Biomed Res, Boston, MA 02115 USA. RP Schmidt-Supprian, M (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM supprian@cbr.med.harvard.edu; rajewsky@cbr.med.harvard.edu RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 NR 34 TC 196 Z9 202 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2007 VL 8 IS 7 BP 665 EP 668 DI 10.1038/nio707-665 PG 4 WC Immunology SC Immunology GA 185NQ UT WOS:000247718100003 PM 17579640 ER PT J AU Fraenkel, S Mostoslavsky, R Novobrantseva, TI Pelanda, R Chaudhuri, J Esposito, G Jung, S Alt, FW Rajewsky, K Cedar, H Bergman, Y AF Fraenkel, Shira Mostoslavsky, Raul Novobrantseva, Tatiana I. Pelanda, Roberta Chaudhuri, Jayanta Esposito, Gloria Jung, Steffen Alt, Frederick W. Rajewsky, Klaus Cedar, Howard Bergman, Yehudit TI Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus SO NATURE IMMUNOLOGY LA English DT Article ID B-CELL DEVELOPMENT; ANTIBODY DIVERSIFICATION; DNA DEAMINATION; GENE-EXPRESSION; MOUSE STRAIN; HEAVY-CHAIN; GERM-LINE; V-GENE; EXCLUSION; TRANSCRIPTION AB Monoallelic demethylation and rearrangement control allelic exclusion of the immunoglobulin kappa-chain locus (Igk locus) in B cells. Here, through the introduction of pre-rearranged Igk genes into their physiological position, the critical rearrangement step was bypassed, thereby generating mice producing B cells simultaneously expressing two different immunoglobulin-kappa light chains. Such 'double- expressing' B cells still underwent monoallelic demethylation at the Igk locus, and the demethylated allele was the 'preferred' substrate for somatic hypermutation in each cell. However, methylation itself did not directly inhibit the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Albylam Pharmaceut, Cambridge, MA 02142 USA. Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Artemis Pharmaceut, D-51063 Cologne, Germany. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Bergman, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel. EM yberg@md2.huji.ac.il NR 49 TC 33 Z9 33 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2007 VL 8 IS 7 BP 715 EP 722 DI 10.1038/ni1476 PG 8 WC Immunology SC Immunology GA 185NQ UT WOS:000247718100012 PM 17546032 ER PT J AU Connor, KM SanGiovanni, JP Lofqvist, C Aderman, CM Chen, J Higuchi, A Hong, S Pravda, EA Majchrzak, S Carper, D Hellstrom, A Kang, JX Chew, EY Salem, N Serhan, CN Smith, LEH AF Connor, Kip M. SanGiovanni, John Paul Lofqvist, Chatarina Aderman, Christopher M. Chen, Jing Higuchi, Akiko Hong, Song Pravda, Elke A. Majchrzak, Sharon Carper, Deborah Hellstrom, Ann Kang, Jing X. Chew, Emily Y. Salem, Norman, Jr. Serhan, Charles N. Smith, Lois E. H. TI Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis SO NATURE MEDICINE LA English DT Article ID NF-KAPPA-B; DOCOSAHEXAENOIC ACID; ISCHEMIC RETINOPATHY; RESOLVIN E1; IN-VIVO; INFLAMMATION; RECEPTOR; NEOVASCULARIZATION; INHIBITION; PROLIFERATION AB Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Univ Gothenburg, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med,Ctr Expt T, Boston, MA 02115 USA. NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. NEI, Off Director, Bethesda, MD 20892 USA. Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Smith, LEH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. EM lois.smith@childrens.harvard.edu RI SanGiovanni, John Paul/A-7605-2008; Majchrzak, Sharon/F-1830-2013; OI Majchrzak, Sharon/0000-0001-8934-7294; Lofqvist, Chatarina/0000-0003-4371-5164; Connor, Kip/0000-0002-2048-9080; Hellstrom, Ann/0000-0002-9259-1244 FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [1F32 EY017789, 5 T32 EY07145, EY008670, EY017017, EY14811, F32 EY017789, R01 EY008670, R01 EY017017, R21 EY014811, T32 EY007145]; NICHD NIH HHS [P01 HD18655, P30 HD018655]; NIDCR NIH HHS [P50 DE016191, P50-DE016191]; NIGMS NIH HHS [GM38765, R01 GM038765, R37 GM038765] NR 30 TC 327 Z9 344 U1 4 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 JUL PY 2007 VL 13 IS 7 BP 868 EP 873 DI 10.1038/nm1591 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 188EU UT WOS:000247902800035 PM 17589522 ER PT J AU Goessling, W North, TE Zon, LI AF Goessling, Wolfram North, Trista E. Zon, Leonard I. TI Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors SO NATURE METHODS LA English DT Article ID THERAPY; FLOW AB Zebrafish are a valuable vertebrate model to study carcinogenesis, but noninvasive imaging is challenging because adult fish are not transparent. Here we show that tumors could be readily detected in vivo using high-resolution microscopic ultrasound in zebrafish. We successfully obtained tissue perfusion calculations and cellular aspirates, and analyzed tumor progression and response to treatment. Ultrasound biomicroscopy allows longitudinal studies of tumor development and real-time assessment of therapeutic effects in zebrafish. C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Howard Hughes Med Inst, Stem Cell Inst,Med Sch, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU NIDDK NIH HHS [5 K08 DK 071940-02] NR 12 TC 53 Z9 59 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JUL PY 2007 VL 4 IS 7 BP 551 EP 553 DI 10.1038/NMETH1059 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 184NL UT WOS:000247648600011 PM 17572681 ER PT J AU Agarwal, N Pacher, P Tegeder, I Amaya, F Constantin, CE Brenner, GJ Rubino, T Michalski, CW Marsicano, G Monory, K Mackie, K Marian, C Batkai, S Parolaro, D Fischer, MJ Reeh, P Kunos, G Kress, M Lutz, B Woolf, CJ Kuner, R AF Agarwal, Nitin Pacher, Pal Tegeder, Irmgard Amaya, Fumimasa Constantin, Cristina E. Brenner, Gary J. Rubino, Tiziana Michalski, Christoph W. Marsicano, Giovanni Monory, Krisztina Mackie, Ken Marian, Claudiu Batkai, Sandor Parolaro, Daniela Fischer, Michael J. Reeh, Peter Kunos, George Kress, Michaela Lutz, Beat Woolf, Clifford J. Kuner, Rohini TI Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors SO NATURE NEUROSCIENCE LA English DT Article ID IN-SITU HYBRIDIZATION; DORSAL-ROOT GANGLIA; NEUROPATHIC PAIN; ENDOGENOUS CANNABINOIDS; SPINAL NEURONS; KNOCKOUT MICE; WIN 55,212-2; RATS; CB1; HYPERALGESIA AB Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in nociceptive neurons localized in the peripheral nervous system of mice, preserving its expression in the CNS, and analyzed these genetically modified mice in preclinical models of inflammatory and neuropathic pain. The nociceptor-specific loss of CB1 substantially reduced the analgesia produced by local and systemic, but not intrathecal, delivery of cannabinoids. We conclude that the contribution of CB1-type receptors expressed on the peripheral terminals of nociceptors to cannabinoid-induced analgesia is paramount, which should enable the development of peripherally acting CB1 analgesic agonists without any central side effects. C1 Univ Heidelberg, Inst Pharmacol, D-69120 Heidelberg, Germany. NIH, NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. Univ Frankfurt Klinikum, D-60590 Frankfurt, Germany. Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Med Univ Innsbruck, Dept Physiol & Med Phys, Div Physiol, A-6020 Innsbruck, Austria. Univ Mainz, Dept Physiol Chem, D-55099 Mainz, Germany. Univ Washington, Sch Med, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany. RP Kuner, R (reprint author), Univ Heidelberg, Inst Pharmacol, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. EM rohini.kuner@pharma.uni-heidelberg.de RI Fischer, Michael/F-7976-2010; Mackie, Kenneth/B-7358-2011; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Reeh, Peter/J-8981-2012; Mackie, Ken/E-3715-2013; Batkai, Sandor/H-7983-2014; OI Pacher, Pal/0000-0001-7036-8108; Reeh, Peter/0000-0002-4367-094X; Mackie, Ken/0000-0001-8501-6199; Tegeder, Irmgard/0000-0001-7524-8025 FU Intramural NIH HHS [Z01 AA000375-02]; NIDA NIH HHS [DA00286, DA11322, K02 DA000286, K02 DA000286-04, R01 DA011322, R01 DA011322-02]; NINDS NIH HHS [NS 038253, NS039518, R01 NS038253, R01 NS038253-01S1, R01 NS039518, R01 NS039518-01A2, R37 NS039518] NR 46 TC 285 Z9 289 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2007 VL 10 IS 7 BP 870 EP 879 DI 10.1038/nn1916 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 183GH UT WOS:000247560200017 PM 17558404 ER PT J AU Kawasaki, T Nosho, K Ohnishi, M Suemoto, Y Kirkner, GJ Dehari, R Meyerhardt, JA Fuchs, CS Ogino, S AF Kawasaki, Takako Nosho, Katsuhiko Ohnishi, Mutsuko Suemoto, Yuko Kirkner, Gregory J. Dehari, Reiko Meyerhardt, Jeffrey A. Fuchs, Charles S. Ogino, Shuji TI Correlation of beta-catenin localization with cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal cancer SO NEOPLASIA LA English DT Article DE colon cancer; CTNNB1; CpG island methylator phenotype; PTGS2; microsatellite instability ID POPULATION-BASED SAMPLE; MICROSATELLITE INSTABILITY; COLON-CANCER; PROMOTER HYPERMETHYLATION; MOLECULAR-FEATURES; EPIGENETIC CHANGES; WNT PATHWAY; MUTATION; APC; CARCINOMAS AB The WNT/beta-catenin (CTNNB1) pathway is commonly activated in the carcinogenic process. Cross- talks between the WNT and cyclooxygenase- 2 (COX-2 or PTGS2)/ prostaglandin pathways have been suggested. The relationship between beta-catenin activation and microsatellite instability (MSI) in colorectal cancer has been controversial. The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, which is associated with MSI-high. However, no study has examined the relationship between beta-catenin activation and CIMP status. Using 832 population-based colorectal cancer specimens, we assessed beta-catenin localization by immunohistochemistry. We quantified DNA methylation ineightCIMP- specific promoters[CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (Methy Light). MSI-high, CIMP-high, and BRAF mutation were associated inversely with cytoplasmic and nuclear beta-catenin expressions (i. e., beta-catenin activation) and associated positively with membrane expression. The inverse relation between beta-catenin activation and CIMP was independent of MSI. COX-2 overexpression correlated with cytoplasmic beta-catenin expression (even after tumors were stratified by CIMP status), but did not correlate significantly with nuclear or membrane expression. In conclusion, beta-catenin activation is inversely associated with CIMP-high independent of MSI status. Cytoplasmic beta-catenin is associated with COX-2 overexpression, supporting the role of cytoplasmic beta-catenin in stabilizing PTGS2 (COX- 2) mRNA. C1 Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Sapporo Med Univ, Dept Internal Med, Sapporo, Hokkaido, Japan. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Kanagawa Canc Ctr, Dept Pathol, Kanagawa, Japan. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst, 44 Binney St,Room JF215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075, P01 CA87969, P01 CA055075, P01 CA087969] NR 48 TC 66 Z9 71 U1 0 U2 6 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL PY 2007 VL 9 IS 7 BP 569 EP 577 DI 10.1593/neo.07334 PG 9 WC Oncology SC Oncology GA 196PS UT WOS:000248495100006 PM 17710160 ER PT J AU Abrey, LE Louis, DN Paleologos, N Lassman, AB Raizer, JJ Mason, W Finlay, J MacDonald, DR DeAngelis, LM Cairncross, JG AF Abrey, Lauren E. Louis, David N. Paleologos, Nina Lassman, Andrew B. Raizer, Jeffrey J. Mason, Warren Finlay, Jonathan MacDonald, David R. DeAngelis, Lisa M. Cairncross, J. Gregory CA Oligodendroglioma Study Grp TI Survey of treatment recommendations for anaplastic oligodendroglioma SO NEURO-ONCOLOGY LA English DT Article DE 1p; 19q; anaplastic oligodendroglioma; molecular genetic studies; radiotherapy; survey; temozolomide; treatment recommendations ID PHASE-II; CHEMOTHERAPY; TEMOZOLOMIDE; PREDICTORS; GLIOBLASTOMA; DIAGNOSIS; SURVIVAL; TUMORS; 1P AB Anaplastic oligodendroglioma is a malignant brain tumor uniquely sensitive to treatment with both chemotherapy and radiotherapy. There are few prospective clinical trials for newly diagnosed patients and multiple approaches to the treatment of these patients. This study explored the recommended treatment offered by experts in neuro-oncology. A Web-based survey was developed and distributed to 800 members of the Society of Neuro-Oncology (SNO) who had an e-mail address listed with SNO. Questions addressed use of molecular genetic information and treatment recommendations. A total of 99 clinical SNO members (20%) responded. The majority reported practicing at an academic center in the United States. Two-thirds of respondents see more than five patients with newly diagnosed anaplastic oligodendroglioma annually. Molecular genetic testing was requested for more than 75% of patients, and the results significantly influenced treatment recommendations (p = 0.000003). Regardless of molecular genetic status, the most commonly recommended treatment was the use of concurrent temozolomide and radiotherapy followed by adjuvant temozolomide (18%-34%). The current survey demonstrates that although neuro-oncologists have embraced the use of molecular genetic studies in newly diagnosed anaplastic oligodendroglioma, treatment recommendations vary widely and are often independent of the molecular data. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Evanston, IL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Calgary, Calgary, AB, Canada. RP Abrey, LE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM abreyl@mskcc.org NR 18 TC 75 Z9 76 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2007 VL 9 IS 3 BP 314 EP 318 DI 10.1215/15228517-2007-002 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 189UL UT WOS:000248014000010 PM 17435180 ER PT J AU Kesari, S Schiff, D Doherty, L Gigas, DC Batchelor, TT Muzikansky, A O'Neill, A Drappatz, J Chen-Plotkin, AS Ramakrishna, N Weiss, SE Levy, B Bradshaw, J Kracher, J Laforme, A Black, PM Folkman, J Kieran, M Wen, PY AF Kesari, Santosh Schiff, David Doherty, Lisa Gigas, Debra C. Batchelor, Tracy T. Muzikansky, Alona O'Neill, Alison Drappatz, Jan Chen-Plotkin, Alice S. Ramakrishna, Naren Weiss, Stephanie E. Levy, Brenda Bradshaw, Joanna Kracher, Jean Laforme, Andrea Black, Peter McL. Folkman, Judah Kieran, Mark Wen, Patrick Y. TI Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults SO NEURO-ONCOLOGY LA English DT Article DE angiogenesis; antiangiogenesis; clinical trial; glioblastoma; metronomic chemotherapy ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; LOW-DOSE CYCLOPHOSPHAMIDE; HIGH-GRADE GLIOMAS; IN-VIVO; BRAIN-TUMORS; ANTIANGIOGENIC THERAPY; ANGIOGENESIS; THALIDOMIDE; GLIOBLASTOMA AB Preclinical evidence suggests that continuous low-dose daily (metronomic) chemotherapy may inhibit tumor endothelial cell proliferation (angiogenesis) and prevent tumor growth. This phase II study evaluated the feasibility of this antiangiogenic chemotherapy regimen in adults with recurrent malignant gliomas. The regimen consisted of low-dose etoposide (35 mg/m(2) [maximum, 100 mg/day] daily for 21 days), alternating every 21 days with cyclophosphamide (2 mg/kg [maximum, 100 mg/day] daily for 21 days), in combination with daily thalidomide and celecoxib, in adult patients with recurrent malignant gliomas. Serum and urine samples were collected for measurement of angiogenic peptides. Forty-eight patients were enrolled ( 15 female, 33 male). Twenty-eight patients had glioblastoma multiforme (GBMs), and 20 had anaplastic gliomas (AGs). Median age was 53 years ( range, 33-74 years), and median KPS was 70 ( range, 60-100). Therapy was reasonably well tolerated in this heavily pretreated population. Two percent of patients had partial response, 9% had a minor response, 59% had stable disease, and 30% had progressive disease. For GBM patients, median progression-free survival (PFS) was 11 weeks, six-month PFS (6M-PFS) was 9%, and median overall survival (OS) was 21 weeks. For AG patients, median PFS was 14 weeks, 6M-PFS was 26%, and median OS was 41.5 weeks. In a limited subset of patients, serum and urine angiogenic peptides did not correlate with response or survival (p > .0.05). Although there were some responders, this four-drug, oral metronomic regimen did not significantly improve OS in this heavily pretreated group of patients who were generally not eligible for conventional protocols. While metronomic chemotherapy may not be useful in patients with advanced disease, further studies using metronomic chemotherapy combined with more potent antiangiogenic agents in patients with less advanced disease may be warranted. C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Virginia, Neurooncol Ctr, Charlottesville, VA USA. Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Childrens Hosp, Vasc Biol Program, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 44 Binney St,SW430D, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013; OI Kieran, Mark/0000-0003-2184-7692 NR 60 TC 71 Z9 73 U1 0 U2 4 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2007 VL 9 IS 3 BP 354 EP 363 DI 10.1215/15228517-2007-006 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 189UL UT WOS:000248014000015 PM 17452651 ER PT J AU Eichler, AF Batchelor, TT Henson, JW AF Eichler, April F. Batchelor, Tracy T. Henson, John W. TI Diffusion and perfusion imaging in subacute neurotoxicity following high-dose intravenous methotrexate SO NEURO-ONCOLOGY LA English DT Article DE adult; diffusion; methotrexate; neurotoxicity ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSIENT ENCEPHALOPATHY; WHITE-MATTER; INTRATHECAL METHOTREXATE; SYSTEMIC METHOTREXATE; OSTEOGENIC-SARCOMA; WEIGHTED MRI; CHEMOTHERAPY; CHILDREN; LEUKOENCEPHALOPATHY AB Methotrexate (MTX) is a widely used chemotherapeutic agent that can cause acute, subacute, and chronic neurological complications. Subacute MTX neurotoxicity is manifest by abrupt onset of focal cerebral dysfunction occurring days to weeks after MTX administration, usually in children. We describe the neuroimaging features of an adult patient with primary CNS lymphoma who presented with transient aphasia and right hemiparesis 12 days after receiving intravenous highdose MTX (8 g/m(2)) chemotherapy. Imaging within 1 h of symptom onset showed bilateral symmetrical restricted diffusion involving white matter of the cerebral hemispheres. CT angiogram and dynamic susceptibility MRI showed no evidence of vasospasm or perfusion defect. MRI five days later showed nearcomplete resolution of the abnormalities. MRI 3 months later showed normal diffusion but new hyperintense T2-weighted signal changes in the subcortical white matter corresponding to previous areas of restricted diffusion. The absence of vascular or perfusion abnormalities suggests that transient cytotoxic edema in white matter may explain the syndrome of subacute MTX neurotoxicity. C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 24 TC 22 Z9 23 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2007 VL 9 IS 3 BP 373 EP 377 DI 10.1215/15228517-2007-015 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 189UL UT WOS:000248014000018 PM 17522329 ER PT J AU Wakana, S Caprihan, A Panzenboeck, MM Fallon, JH Perry, M Gollub, RL Hua, KG Zhang, JY Jiang, HY Dubey, P Blitz, A van Zijl, P Mori, S AF Wakana, Setsu Caprihan, Arvind Panzenboeck, Martina M. Fallon, James H. Perry, Michele Gollub, Randy L. Hua, Kegang Zhang, Jiangyang Jiang, Hangyi Dubey, Prachi Blitz, Ari van Zijl, Peter Mori, Susumu TI Reproducibility of quantitative tractography methods applied to cerebral white matter SO NEUROIMAGE LA English DT Article DE diffusion tensor imaging; tractography; reproducibility; white matter ID DIFFUSION TENSOR MRI; HUMAN BRAIN; IN-VIVO; AXONAL PROJECTIONS; MULTIPLE-SCLEROSIS; DT-MRI; TRACT; TRACKING; ARCHITECTURE; ASYMMETRY AB Tractography based on diffusion tensor imaging (DTI) allows visualization of white matter tracts. In this study, protocols to reconstruct eleven major white matter tracts are described. The protocols were refined by several iterations of intra- and inter-rater measurements and identification of sources of variability. Reproducibility of the established protocols was then tested by raters who did not have previous experience in tractography. The protocols were applied to a DTI database of adult normal subjects to study size, fractional anisotropy (FA), and T-2 of individual white matter tracts. Distinctive features in FA and T-2 were found for the corticospinal tract and callosal fibers. Hemispheric asymmetry was observed for the size of white matter tracts projecting to the temporal lobe. This protocol provides guidelines for reproducible DTI-based tract-specific quantification. (c) 2007 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Kennedy Krieger Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD 21205 USA. New Mexico Resonance, Albuquerque, NM 87106 USA. MIND Inst, Albuquerque, NM 87106 USA. Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Mori, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, 217 Traylar Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM susumu@mri.jhu.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NCRR NIH HHS [P41 RR015241, P41 RR015241-01A1, P41RR15241, U24 RR021382, U24 RR021382-01, U24RR021382]; NIA NIH HHS [R01 AG020012-02, R01 AG020012, R01 AG020012-01, R01 AG020012-03, R01 AG020012-04, R01 AG020012-05, R01 AG020012-06A1, R01AG20012]; NIBIB NIH HHS [P41 EB015909] NR 35 TC 605 Z9 613 U1 1 U2 36 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 JUL 1 PY 2007 VL 36 IS 3 BP 630 EP 644 DI 10.1016/j.neuroimage.2007.02.049 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 184IJ UT WOS:000247634400013 PM 17481925 ER PT J AU Yang, J Sadler, TR Givrad, TK Maarek, JMI Holschneider, DP AF Yang, J. Sadler, T. R. Givrad, T. K. Maarek, J.-M. I. Holschneider, D. P. TI Changes in brain functional activation during resting and locomotor states after unilateral nigrostriatal damage in rats SO NEUROIMAGE LA English DT Review DE brain mapping; functional neuroimaging; cerebral blood flow; plasticity; hemiparkinsonism; Parkinson's disease ID CEREBRAL-BLOOD-FLOW; PARKINSONS-DISEASE BEGIN; SUPPLEMENTARY MOTOR AREA; BASAL GANGLIA; SUBSTANTIA-NIGRA; CAUDATE-PUTAMEN; VENTRAL SUBICULUM; INDICATOR FRACTIONATION; SUBTHALAMIC NUCLEUS; STRIATAL DOPAMINE AB To evaluate functional neuronal compensation after partial damage to the nigrostriatal system, we lesioned rats unilaterally in the striatum with 6-hydroxydopamine. Five weeks later, cerebral perfusion was mapped at rest or during treadmill walking using [C-14]-iodoantipyrine. Regional CBF-related tissue radioactivity (CBF-TR) was quantified by autoradiography and analyzed by statistical parametric mapping and region-of-interest analysis. Lesions were confirmed by tyrosine hydroxylase immunohistochemistry and changes in rotational locomotor activity. Functional compensations were bilateral and differed at rest and during treadmill walking. Consistent with the classic view of striatopallidal connections, CBF-TR of lesioned compared to sham-lesioned rats increased in the ipsilateral subthalamic nucleus (STN) and internal globus pallidus, and decreased in the striatum and external globus pallidus. Contrary to the classic view, CBF-TR increased in the ipsilateral ventral lateral, ventral anterior thalamus and motor cortex, as well as in the central medial thalamus, midline cerebellum, and contralateral STN. During walking, perfusion decreased in lesioned compared to sham-lesioned rats across the ipsilateral striato-pallidal-thalamic-cortical motor circuit. Compensatory increases were seen bilaterally in the ventromedial thalamus and red nucleus, in the contralateral STN, anterior substantia nigra, subiculum, motor cortex, and in midline cerebellum. Enhanced recruitment of associative sensory areas was noted cortically and subcortically. Future models of compensatory changes after nigrostriatal damage need to address the effects of increased neural activity by residual dopaminergic neurons, interhemispheric interactions and differences between resting and locomotor states. Identification of sites at which functional compensation occurs may define useful future targets for neurorehabilitative or neurorestorative interventions in Parkinson's disease. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90003 USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Engn, Dept Biomed Engn, Los Angeles, CA 90089 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Holschneider, DP (reprint author), Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, 1333 San Pablo St,BMT 403,MC 9112, Los Angeles, CA 90003 USA. EM holschne@usc.edu FU NINDS NIH HHS [1R01 NS050171, R01 NS050171-02, R01 NS050171-03, R01 NS050171] NR 103 TC 31 Z9 32 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2007 VL 36 IS 3 BP 755 EP 773 DI 10.1016/j.neuroimage.2007.03.010 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 184IJ UT WOS:000247634400025 PM 17481921 ER PT J AU Davis, JA Costello, DJ Venna, N AF Davis, John A. Costello, Daniel J. Venna, Nagagopal TI Laboratory investigation of fungal infections of the central nervous system SO NEUROLOGY INDIA LA English DT Review DE Fungal encephalitis; fungal infection; fungal meningitis AB While fungal infections of the central nervous system (CNS) are relatively rare, fungal pathogens are increasingly being recognized as an important etiology of CNS infections, particularly amongst the growing immunocompromized population. In this paper we aim to provide a practical approach to the diagnosis of fungal infections of the CNS, review some of the diagnostic methods currently available and discuss diagnosis of certain pathogens of particular interest to the practicing neurologist. C1 [Davis, John A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Costello, Daniel J.; Venna, Nagagopal] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Venna, N (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM nvenna1@partners.org NR 50 TC 7 Z9 7 U1 0 U2 0 PU MEDKNOW PUBLICATIONS PI MUMBAI PA A-108-109 KANARA BUSINESS CENTRE, GHAKTOPAR, MUMBAI, 400075, INDIA SN 0028-3886 J9 NEUROL INDIA JI Neurol. India PD JUL-SEP PY 2007 VL 55 IS 3 BP 233 EP 240 PG 8 WC Neurosciences SC Neurosciences & Neurology GA V01RC UT WOS:000206871700008 PM 17921652 ER PT J AU White, DK Wagenaar, RC Del Olmo, ME Ellis, TD AF White, Daniel K. Wagenaar, Robert C. Del Olmo, Mary E. Ellis, Terry D. TI Test-retest reliability of 24 hours of activity monitoring in individuals with Parkinson's disease in home and community SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE activity monitoring; Parkinson's disease; physical activities; accelerometry ID PHYSICAL-ACTIVITY LEVELS; AMBULATORY ACCELEROMETRY; GENERALIZABILITY THEORY; HEART-FAILURE; VARIABILITY; VALIDITY; LIFE; QUANTIFY; VARIANCE; BEHAVIOR AB Background/Objective. This study examined the test-retest reliability of an activity monitor (AM) in home and community settings in individuals with Parkinson's disease (PD). Methods. Nine independent community dwellers with idiopathic PD were recruited (8 males and 1 female; median age = 66 years, range 46-71; Hoehn & Yahr score 2). Patients wore the AM for 3 separate sessions in the home and community with 7 days between each session. The first 2 sessions lasted 24 hours each, and the third session lasted 48 hours. Reliability indices and measures of variability were obtained by using intraclass correlation coefficients (ICC) and generalizability coefficients. The functional activity measures included the percentage of time spent in sleeping positions, sitting, standing, and walking; the number of transitions between sit and stand; the total number of transitions; the number of walking periods lasting 5 and 10 seconds; and stride frequency. Results. The ICCs for functional activities between the first and second consecutive days for the 48-hour session (third session) ranged from .76 to .92. The ICCs for the 7- and 14-day intervals ranged from .45 to .96, with walking-related measures showing the highest ICCs (range = .81 to.96). Across the three 24-hour periods (sessions 1 and 2, and the First 24 hours of session 3), the ICCs for walking-related measures were again high ranging from.87 to.92. Walking-related measures demonstrated the highest generalizability coefficients, indicating these measures have the highest test-retest reliability in comparison to other functional activity measures. Conclusions. The present study shows that 24 hours of recording with an AM is a sufficient duration of time to reliably record patients' functional activity in the home and community settings. In addition, the highest test-retest reliability for activities across 7- and 14-day intervals were found for walking-related measures in individuals with PD, indicating these measures have the highest stability compared to the other measures of functional activity. C1 Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Phys Therapy & Athlet Training, Ctr Neurorehabil, Boston, MA 02215 USA. Boston Univ, Sargent Coll Hlth & Rehabil Sci, Program Rehabil Sci ScD, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wagenaar, RC (reprint author), Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Phys Therapy & Athlet Training, Ctr Neurorehabil, 635 Commonwealth Ave, Boston, MA 02215 USA. EM wagenaar@bu.edu FU NIA NIH HHS [R01 AG021152] NR 40 TC 23 Z9 23 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD JUL-AUG PY 2007 VL 21 IS 4 BP 327 EP 340 DI 10.1177/1545968306297867 PG 14 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 179UC UT WOS:000247314600005 PM 17369513 ER PT J AU Dickerson, BC AF Dickerson, Bradford C. TI Advances in functional magnetic resonance imaging: Technology and Clinical Applications SO NEUROTHERAPEUTICS LA English DT Review DE Alzheimer's disease; mild cognitive impairment; plasticity; functional magnetic resonance imaging. ID MILD COGNITIVE IMPAIRMENT; TEMPORAL-LOBE ACTIVATION; EARLY ALZHEIMERS-DISEASE; HUMAN AUDITORY-CORTEX; BRAIN ACTIVATION; WORKING-MEMORY; CHOLINERGIC ENHANCEMENT; PHARMACOLOGICAL FMRI; MULTIPLE-SCLEROSIS; OLDER-ADULTS AB Functional MRI (fMRI) is a valuable method for use by clinical investigators to study task-related brain activation in patients with neurological or neuropsychiatric illness. Despite the relative infancy of the field, the rapid adoption of this functional neuroimaging technology has resulted from, among other factors, its ready availability, its relatively high spatial and temporal resolution, and its safety as a noninvasive imaging tool that enables multiple repeated scans over the course of a longitudinal study, and thus may lend itself well as a measure in clinical drug trials. Investigators have used fMRI to identify abnormal functional brain activity during task performance in a variety of patient populations, including those with neurodegenerative, demyelinating, cerebrovascular, and other neurological disorders that highlight the potential utility of fMRI in both basic and clinical spheres of research. In addition, fMRI studies reveal processes related to neuroplasticity, including compensatory hyperactivation, which may be a universally-occurring, adaptive neural response to insult. Functional MRI is being used to study the modulatory effects of genetic risk factors for neurological disease on brain activation; it is being applied to differential diagnosis, as a predictive biomarker of disease course, and as a means to identify neural correlates of neurotherapeutic interventions. Technological advances are rapidly occurring that should provide new applications for fMRI, including improved spatial resolution, which promises to reveal novel insights into the function of fine-scale neural circuitry of the human brain in health and disease. C1 Massachusetts Gen Hosp, Res Alzheimers Dis Ctr, Athinoula A Martinos Ctr Biomed Imaging, Gerontol Res Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Memory Disorders Unit, Boston, MA 02129 USA. Harvard Med Sch, Dept Neurol, Charlestown, MA 02129 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41-RR14075]; NIA NIH HHS [K23-AG22509] NR 109 TC 20 Z9 22 U1 5 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JUL PY 2007 VL 4 IS 3 BP 360 EP 370 DI 10.1016/j.nurt.2007.05.007 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 214UD UT WOS:000249762800005 PM 17599702 ER PT J AU Heaton, KJ Palumbo, CL Proctor, SP Killiany, RJ Yurgelun-Todd, DA White, RF AF Heaton, Kristin J. Palumbo, Carole L. Proctor, Susan P. Killiany, Ronald J. Yurgelun-Todd, Deborah A. White, Roberta F. TI Quantitative magnetic resonance brain imaging in US army veterans of the 1991 Gulf War potentially exposed to sarin and cyclosarin SO NEUROTOXICOLOGY LA English DT Article DE magnetic resonance imaging; morphometric analyses; brain; central nervous system; chemical warfare agents; sarin; cyclosarin; Gulf War veterans; khamisiyah; Iraq ID POSTTRAUMATIC-STRESS-DISORDER; CHEMICAL MUNITIONS DESTRUCTION; WHITE-MATTER CHANGES; LOW-LEVEL EXPOSURE; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; MR SPECTROSCOPY; NERVOUS-SYSTEM; GUINEA-PIGS; KHAMISIYAH AB Background: In March 1991, a munitions storage complex at Khamisiyah, Iraq was destroyed, potentially exposing more than 100,000 US troops to low levels of the organophosphate nerve agents sarin and cyclosarin. Little is known about the neurophysiological effects of low-dose exposure to sarin/cyclosarin in humans, although some research has indicated subtle but persistent neurobehavioral and neurochemical changes in individuals exposed to sarin/cyclosarin at levels insufficient to produce obvious clinical symptoms. However, the neuroanatomical correlates of these changes are unclear. The current study examined the association between modeled estimates of sarin/cyclosarin exposure levels and volumetric measurements of gross neuroanatomical structures in 1991 Gulf War veterans with varying degrees of possible low-level sarin/cyclosarin exposure. Methods: Twenty-six GW-deployed veterans recruited from the Devens Cohort Study participated. Magnetic resonance images of the brain were acquired and analyzed using morphometric techniques, producing volumetric measurements of white matter, gray matter, right and left lateral ventricles, and cerebrospinal fluid. Volumetric data were analyzed using exposure estimates obtained from refined models of the 1991 Khamisiyah presumed exposure hazard area. Results: Binary comparisons of sarin/cyclosarin 'exposed' (N = 13) and 'unexposed' (N = 13) veterans revealed no differences in volumetric measurements of discrete brain tissues. However, linear trend analyses showed a significant association between higher levels of estimated sarin/cyclosarin exposure and both reduced white matter (adjusted parameter estimate = -4.64, p < 0.0001) and increased right lateral ventricle (adjusted parameter estimate = .11, p = 0.0288) and left lateral ventricle (adjusted parameter estimate =.13, p < 0.0001) volumes. Conclusions: These findings suggest subtle but persistent central nervous system pathology in Gulf War veterans potentially exposed to low levels of sarin/cyclosarin and argue for further investigation of the long-term effects of low-dose sarin/cyclosarin exposures in humans. (c) 2007 Elsevier Inc. All rights reserved. C1 USA, Environm Med Res Inst, Med Performance Div, Mil Performance Div, Natick, MA 01760 USA. Boston Environm Hazards Res Ctr, VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. RP Heaton, KJ (reprint author), USA, Environm Med Res Inst, Med Performance Div, Mil Performance Div, Bldg 42,Kansas St, Natick, MA 01760 USA. EM kristin.heaton@us.army.mil RI Heaton, Kristin/E-3660-2013 NR 65 TC 46 Z9 46 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUL PY 2007 VL 28 IS 4 BP 761 EP 769 DI 10.1016/j.neuro.2007.03.006 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 202BC UT WOS:000248875500006 PM 17485118 ER PT J AU Burns, EK Levinson, AH Lezotte, D Prochazka, AV AF Burns, Emily K. Levinson, Arnold H. Lezotte, Dennis Prochazka, Allan V. TI Differences in smoking duration between Latinos and Anglos SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CIGARETTE-SMOKING; SOCIOECONOMIC-STATUS; LUNG-CANCER; CESSATION; BEHAVIOR; SMOKERS; RESTRICTIONS; EPIDEMIOLOGY; INITIATION; HOUSEHOLD AB A smoker's risk of disease and death from cigarettes is related directly to the duration of smoking. The present study compared duration of smoking between a state-level population of Anglo versus highly acculturated Latino ever-smokers (N=6,100). Kapla-Meier analysis was used to obtain weighted median smoking duration. Weighted Cox proportional hazard models were used to evaluate the relative likelihood of continued smoking, adjusted for demographics, smoking history, home and workplace smoking restrictions, and socioeconomic covariates (education, health insurance status, and poverty level). On average, Latinos continued smoking longer than Anglos (M=30 years vs. 27 years; weighted Cox HR=0.73; 95% CI=0.60-0.89). The disparity remained significant when adjusted for demographic, smoking history, and smoking-rule covariates but was not significant when adjusted for socioeconomic status (HR=0.89, 95%, CI=0.73-1.09). Education alone accounted for the majority of the disparity, more so than poverty or health insurance status. We conclude that highly acculturated Latino smokers may be at greater risk of cigarette disease and death related to longer duration of smoking associated with lower socioeconomic status. C1 Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. AMC Canc Res Ctr, Lakewood, CO USA. Denver VA Med Ctr, Denver, CO USA. RP Burns, EK (reprint author), 1600 Pierce St, Denver, CO 80214 USA. EM emily.burns@uchsc.edu RI Levinson, Arnold/L-3274-2013; OI Levinson, Arnold/0000-0003-3167-0384 NR 34 TC 14 Z9 14 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUL PY 2007 VL 9 IS 7 BP 731 EP 737 DI 10.1080/14622200701397882 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 189GR UT WOS:000247977900003 PM 17577802 ER PT J AU Sander, JD Zaback, P Joung, JK Voytas, DF Dobbs, D AF Sander, Jeffry D. Zaback, Peter Joung, J. Keith Voytas, Daniel F. Dobbs, Drena TI Zinc Finger Targeter (ZiFiT): An engineered zinc finger/target site design tool SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ARTIFICIAL TRANSCRIPTION FACTORS; HOMOLOGOUS RECOMBINATION; RESTRICTION ENZYMES; CHIMERIC NUCLEASES; DNA-RECOGNITION; HUMAN-CELLS; CONSTRUCTION; PROTEINS; DOMAINS; GENE AB Zinc Finger Targeter (ZiFiT) is a simple and intuitive web-based tool that facilitates the design of zinc finger proteins (ZFPs) that can bind to specific DNA sequences. The current version of ZiFiT is based on a widely employed method of ZFP design, the 'modular assembly' approach, in which pre-existing individual zinc fingers are linked together to recognize desired target DNA sequences. Several research groups have described experimentally characterized zinc finger modules that bind many of the 64 possible DNA triplets. ZiFiT leverages the combined capabilities of three of the largest and best characterized module archives by enabling users to select fingers from any of these sets. ZiFiT searches a query DNA sequence for target sites for which a ZFP can be designed using modules available in one or more of the three archives. In addition, ZiFiT output facilitates identification of specific zinc finger modules that are publicly available from the Zinc Finger Consortium. ZiFiT is freely available at http://bindr.gdcb.iastate.edu/ZiFiT/. C1 [Sander, Jeffry D.; Zaback, Peter; Voytas, Daniel F.; Dobbs, Drena] Iowa State Univ, Dept Genet Dev & Cell Biol, Bioinformat & Computat Biol Program, Ames, IA 50011 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sander, JD (reprint author), Iowa State Univ, Dept Genet Dev & Cell Biol, Bioinformat & Computat Biol Program, Ames, IA 50011 USA. EM jdsander@iastate.edu FU NIGMS NIH HHS [GM0699006, GM072621, R01 GM072621, GM066387, R21 GM066387, R33 GM066387, R33 GM066387-04]; NIH HHS [DP1 OD006862] NR 27 TC 110 Z9 116 U1 2 U2 7 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 JUL PY 2007 VL 35 SU S BP W599 EP W605 DI 10.1093/nar/gkm349 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293CD UT WOS:000255311500112 PM 17526515 ER PT J AU Topalkara, A Ben-Arie-Weintrob, Y Ferry, JA Foster, CS AF Topalkara, A. Ben-Arie-Weintrob, Y. Ferry, J. A. Foster, C. S. TI Conjunctival marginal zone B-cell lymphoma (MALT lymphoma) with amyloid and relapse in the stomach SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE amyloid; B-cell; conjunctiva; lymphoma; stomach ID TISSUE LYMPHOMA AB The authors report a localized (primary) conjunctival marginal zone-B-cell lymphoma (mucosa-associated lymphold tissue (MALT)-type), with amylold deposition with relapse in the stomach, 14 months after the initial diagnosis. Ocular adnexal marginal zone B-cell MALT lymphoma is often localized at diagnosis; some relapse in typical MALT sites. There are few reports of localized conjunctival lymphoma with a relapse in the stomach. The authors suggest that all patients with localized ocular adnexal lymphoma be followed for an extended period. C1 Harvard Univ, Sch Med, Massachusetts Eye Res & Surg inst, Ocular Immunol & Uveitis Fdn, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye Res & Surg inst, Ocular Immunol & Uveitis Fdn, 8th Floor 5 Cmbridge Ctr, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 10 TC 6 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JUL-AUG PY 2007 VL 15 IS 4 BP 347 EP 350 DI 10.1080/09273940701375410 PG 4 WC Ophthalmology SC Ophthalmology GA 207RI UT WOS:000249268400009 PM 17763134 ER PT J AU Demichelis, F Fall, K Perner, S Andren, O Schmidt, F Setlur, SR Hoshida, Y Mosquera, JM Pawitan, Y Lee, C Adami, HO Mucci, LA Kantoff, PW Andersson, SO Chinnaiyan, AM Johansson, JE Rubin, MA AF Demichelis, F. Fall, K. Perner, S. Andren, O. Schmidt, F. Setlur, S. R. Hoshida, Y. Mosquera, J-M Pawitan, Y. Lee, C. Adami, H-O Mucci, L. A. Kantoff, P. W. Andersson, S-O Chinnaiyan, A. M. Johansson, J-E Rubin, M. A. TI TMPRSS2 : ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort SO ONCOGENE LA English DT Article DE prostate cancer; cancer-specific death; prognosis; TMPRSS2 : ETS; ERG ID RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; NATURAL-HISTORY; SURVIVAL; SWEDEN; DEATH AB The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may de. ne risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio = 2.7, P < 0.01, 95% confidence interval = 1.3-5.8). Quantitative reverse-transcription-polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2: ERG fusion (P < 0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. ITCirst, SRA, Bioinformat Grp, Trenton, NJ USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Univ Hosp Ulm, Inst Pathol, Ulm, Germany. Orebro Univ Hosp, Dept Urol, Orebro, Sweden. Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Urol AMC, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pathol AMC, Ann Arbor, MI USA. RP Rubin, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 221 Longwood Ave,EBRC 442A, Boston, MA 02115 USA. EM marubin@partners.org RI Fall, Katja/A-9186-2012; OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631; Fall, Katja/0000-0002-3649-2639 FU NCI NIH HHS [P50 CA090381, UO1CA113913]; NIA NIH HHS [R01AG21404] NR 21 TC 358 Z9 369 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2007 VL 26 IS 31 BP 4596 EP 4599 DI 10.1038/sj.onc.1210237 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 187GR UT WOS:000247836100014 PM 17237811 ER PT J AU Minami, Y Shimamura, T Shah, K LaFramboise, T Glatt, KA Liniker, E Borgman, CL Haringsma, HJ Feng, W Weir, BA Lowell, AM Lee, JC Wolf, J Shapiro, GI Wong, KK Meyerson, M Thomas, RK AF Minami, Y. Shimamura, T. Shah, K. LaFramboise, T. Glatt, K. A. Liniker, E. Borgman, C. L. Haringsma, H. J. Feng, W. Weir, B. A. Lowell, A. M. Lee, J. C. Wolf, J. Shapiro, G. I. Wong, K-K Meyerson, M. Thomas, R. K. TI The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272 SO ONCOGENE LA English DT Article DE lung cancer; targeted therapy; oncogene mutation; ERBB2; Her-2; kinase inhibitors ID GROWTH-FACTOR RECEPTOR; EGF RECEPTOR; ACQUIRED-RESISTANCE; KINASE DOMAIN; CELL-LINES; BCR-ABL; GEFITINIB; MUTATIONS; ERLOTINIB; ADENOCARCINOMAS AB Mutations in the ERBB2 gene were recently found in approximately 2% of primary non-small cell lung cancer (NSCLC) specimens; however, little is known about the functional consequences and the relevance to responsiveness to targeted drugs for most of these mutations. Here, we show tha t the major lung cancer-derived ERBB2 mutants, including the most frequent mutation, A775insYVMA, lead to oncogenic transformation in a cellular assay. Murine cells transformed with these mutants were relatively resistant to the reversible epidermal growth factor receptor (EGFR) inhibitor erlotinib, resembling the resistant phenotype found in cells carrying the homologous mutations in exon 20 of EGFR. However, the same cells were highly sensitive to the irreversible dual-specificity EGFR/ERBB2 kinase inhibitor HKI-272, as were those overexpressing wild-type ERBB2. Finally, the NSCLC cell line, Calu-3, overexpressing wild-type ERBB2 owing to a high-level amplification of the ERBB2 gene were highly sensitive to HKI-272. These results provide a rationale for treatment of patients with ERBB2-mutant or ERBB2-amplified lung tumors with HKI-272. C1 Univ Cologne, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany. Univ Cologne, Fac Med, D-50931 Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Cologne, Ctr Integrated Oncol, Dept Internal Med 1, D-5000 Cologne 41, Germany. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. RP Thomas, RK (reprint author), Univ Cologne, Klaus Joachim Zulch Labs, Max Planck Soc, Gleueler Str 50, D-50931 Cologne, Germany. EM geoffrey_Shapiro@dfci.harvard.edu; kwong1@partners.org; matthew_meyerson@dfci.harvard.edu; roman.thomas@nf.mpg.de RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [P20 CA90578] NR 26 TC 51 Z9 53 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2007 VL 26 IS 34 BP 5023 EP 5027 DI 10.1038/sj.onc.1210292 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 194CV UT WOS:000248322500015 PM 17311002 ER PT J AU Moy, B Goss, PE AF Moy, Beverly Goss, Paul E. TI Lapatinib-associated toxicity and practical management recommendations SO ONCOLOGIST LA English DT Article DE lapatinib; dual tyrosine kinase inhibitor; breast cancer; EGFR; ErbB-1; ErbB-2; HER-2; toxicity ID GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; CELL LUNG-CANCER; TYROSINE-KINASE INHIBITORS; PHASE-II TRIAL; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; PROGNOSTIC VALUE; IN-VITRO; TRASTUZUMAB AB Lapatinib is an oral receptor tyrosine kinase inhibitor, inhibiting both the ErbB-1 and ErbB-2 receptors. Lapatinib has been shown to have activity in ErbB-2overexpressing breast cancer in several phase II and III clinical trials. Specifically, lapatinib is effective in patients with metastatic breast cancer, with inflammatory breast cancer, and possibly, with brain metastases. An ongoing clinical trial and another anticipated clinical trial will investigate lapatinib as adjuvant treatment in early-stage disease. Lapatinib has specific toxicities, the most common being diarrhea and rash. Cardiac toxicity is rarely seen with lapatinib. This paper reviews lapatinib-associated toxicities and provides practical management recommendations based on available data. C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Moy, B (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, 55 Fruit St,Lawrence House,LRH 304, Boston, MA 02114 USA. EM bmoy@partners.org NR 57 TC 65 Z9 67 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUL PY 2007 VL 12 IS 7 BP 756 EP 765 DI 10.1634/theoncologist.12-7-756 PG 10 WC Oncology SC Oncology GA 195JM UT WOS:000248408500001 PM 17673607 ER PT J AU Eichler, AF Loeffler, JS AF Eichler, April F. Loeffler, Jay S. TI Multidisciplinary management of brain Metastases SO ONCOLOGIST LA English DT Review DE neoplasm metastasis; brain neoplasms; therapeutics; ionizing radiation; drug therapy ID CELL LUNG-CANCER; PHASE-II TRIAL; PROPHYLACTIC CRANIAL IRRADIATION; RECURSIVE PARTITIONING ANALYSIS; NERVOUS-SYSTEM METASTASES; GAMMA-KNIFE RADIOSURGERY; DISSEMINATED MALIGNANT-MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; RADIATION-THERAPY; RANDOMIZED-TRIAL AB Metastatic brain tumors are the most common intracranial neoplasms in adults. The incidence of brain metastases appears to be rising as a result of superior imaging modalities, earlier detection, and more effective treatment of systemic disease. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and chemotherapy. Treatment decisions must take into account clinical prognostic factors in order to maximize survival and neurologic function whilst avoiding unnecessary treatments. The goal of this article is to review important prognostic factors that may guide treatment selection, discuss the roles of surgery, radiation, and chemotherapy in the treatment of patients with brain metastases, and present new directions in brain metastasis therapy under active investigation. In the future, patients will benefit from a multidisciplinary approach focused on the integration of surgical, radiation, and chemotherapeutic options with the goal of prolonging survival, preserving neurologic and neurocognitive function, and maximizing quality of life. C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Eichler, AF (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM aeichler@partners.org NR 132 TC 152 Z9 162 U1 1 U2 15 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUL PY 2007 VL 12 IS 7 BP 884 EP 898 DI 10.1634/theoncologist.12-7-884 PG 15 WC Oncology SC Oncology GA 195JM UT WOS:000248408500014 PM 17673619 ER PT J AU DeSanto-Madeya, S Bauer-Wu, S Gross, A AF DeSanto-Madeya, Susan Bauer-Wu, Susan Gross, Abigail TI Activities of daily living in women with advanced breast cancer SO ONCOLOGY NURSING FORUM LA English DT Article C1 Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. Emory Univ, Atlanta, GA 30322 USA. Columbia Univ, Sch Nursing, New York, NY 10027 USA. Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA USA. RP DeSanto-Madeya, S (reprint author), Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. EM susan.desantomadeya@umb.edu NR 0 TC 5 Z9 5 U1 1 U2 6 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2007 VL 34 IS 4 BP 841 EP 846 DI 10.1188/07.ONF.841-846 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA 189TC UT WOS:000248010400012 PM 17723984 ER PT J AU Agaimy, A Pelz, AF Corless, CL Wunsch, PH Heinrich, MC Hofstaedter, F Dietmaier, W Blanke, CD Wieacker, P Roessner, A Hartmann, A Schneider-Stock, R AF Agaimy, Abbas Pelz, Antje-Friederike Corless, Christopher L. Wuensch, Peter H. Heinrich, Michael C. Hofstaedter, Ferdinand Dietmaier, Wolfgang Blanke, Charles D. Wieacker, Peter Roessner, Albert Hartmann, Arndt Schneider-Stock, Regine TI Epithelioid gastric stromal tumours of the antrum in young females with the Carney triad: A report of three new cases with mutational analysis and comparative genomic hybridization SO ONCOLOGY REPORTS LA English DT Article DE gastrointestinal stromal tumour; Carney triad; comparative genomic hybridization; PDGFRA; KIT mutations ID OF-THE-LITERATURE; EXTRA-ADRENAL PARAGANGLIOMA; AUTONOMIC NERVE TUMORS; COPY NUMBER CHANGES; PULMONARY CHONDROMA; EXTRAADRENAL PARAGANGLIOMA; 12-YEAR-OLD GIRL; KIT; IMATINIB; ADULTS AB Carney triad is a rare non-hereditary condition affecting young females and characterized by metachronous or synchronous occurrence of epithelioid gastrointestinal stromal tumours (GISTs), pulmonary chondroma and extra-adrenal paraganglioma. The genetic alterations in Carney triad-related GISTs have not been well studied. We evaluated GISTs from three females with incomplete Carney triad for KIT and PDGFRA mutations and studied the DNA by comparative genomic hybridization (CGH). All GISTs originated in the antrum and had a monotonous epithelioid morphology. Two patients had GISTs and pulmonary chondroma and one had GISTs and paraganglioma. Initial manifestation was GIST (n=1), pulmonary chondroma (n=1) and bladder paraganglioma (n=1). Time to the second component was 2-13 years. Two patients were alive at 108 and 168 months (one with metastases) and one died of the disease 3 years later. All cases were wild-type for KIT exons 9, 11 13. 17 and PDGFRA exons 12 and 18. CGH revealed 14 aberrations (mean, 4.7/tumour) including I I gains (X, 1q, 5p, 8q 9p 12p 13q, 18p, 19q), 2 amplifications (1q, 19p) and one loss (13q). Carney triad-related GISTs do not only lack conventional KIT and PDGFRA mutations, but they also lack the non-random loss of 14q and 22q characteristic of their sporadic counterparts, suggesting an origin through a distinct pathogenetic pathway. C1 Klinikum Nurnberg, Inst Pathol, D-90419 Nurnberg, Germany. Univ Magdeburg, Inst Human Genet, D-39106 Magdeburg, Germany. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Univ Regensburg, Inst Pathol, D-8400 Regensburg, Germany. Portland VA Med Ctr, Portland, OR USA. Univ Magdeburg, Inst Pathol, D-39106 Magdeburg, Germany. RP Agaimy, A (reprint author), Klinikum Nurnberg, Inst Pathol, Prof Ernst Nathan Str 1, D-90419 Nurnberg, Germany. EM abbas.agaimy@klinikum-nuernberg.de RI Schneider-Stock, Regine/H-8863-2012 NR 35 TC 27 Z9 29 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JUL PY 2007 VL 18 IS 1 BP 9 EP 15 PG 7 WC Oncology SC Oncology GA 184GU UT WOS:000247629900002 PM 17549339 ER PT J AU Dutcheshen, NT Reinold, MM Gill, TJ AF Dutcheshen, Nicholas T. Reinold, Michael M. Gill, Thomas J. TI Superior labrum anterior posterior lesions in the overhead athlete: Current options for treatment SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE LA English DT Article DE shoulder; SLAP; labrum; overhead athlete; operative technique ID SLAP LESIONS; GLENOID LABRUM; ROTATOR CUFF; SHOULDER; DIAGNOSIS; BICEPS; ARTHROGRAPHY; VARIANTS; COMPLEX; TEARS AB Superior labrum anterior posterior (SLAP) lesions are a common occurrence in today's active society. These lesions can result in significant pain and dysfunction around the shoulder. Since they were first described more than 20 years ago, there have been many different treatment options described, depending on the type of SLAP tear encountered. This article will review the anatomy, classification, diagnosis, treatment, and rehabilitation after surgical treatment for SLAP lesions. The article will also review the authors' preferred surgical technique for addressing SLAP tears in overhead-th rowing athletes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Div Sports Med, Boston, MA USA. Boston Red Sox, Boston, MA USA. RP Dutcheshen, NT (reprint author), Massachusetts Gen Hosp, Div Sports Med, 175 Cambridge St,Suite 470, Boston, MA 02114 USA. EM ndutcheshen@partners.org NR 20 TC 1 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1060-1872 J9 OPER TECHN SPORT MED JI Oper. Tech. Sports Med. PD JUL PY 2007 VL 15 IS 3 BP 96 EP 104 DI 10.1053/j.otsm.2007.05.001 PG 9 WC Sport Sciences; Surgery SC Sport Sciences; Surgery GA 192IW UT WOS:000248195800002 ER PT J AU Ghanem, RC de la Cruz, J Tobaigy, FM Ang, LPK Azar, DT AF Ghanem, Ramon C. de la Cruz, Jose Tobaigy, Faisal M. Ang, Leonard P. K. Azar, Dimitri T. TI LASIK in the presbyopic age group - Safety, efficacy, and predictability in 40-to 69-year-old patients SO OPHTHALMOLOGY LA English DT Article ID IN-SITU KERATOMILEUSIS; ACADEMY-OF-OPHTHALMOLOGY; BEAVER DAM EYE; PHOTOREFRACTIVE KERATECTOMY; REFRACTIVE SURGERY; ADULT-POPULATION; MONOVISION; MYOPIA; ENHANCEMENT; RETREATMENT AB Objective: To report the safety, efficacy, and predictability of LASIK in a presbyopic population and to examine possible differences between age groups. Design: Retrospective, descriptive, comparative consecutive case series. Participants: Seven hundred ten eyes of 424 patients between 40 and 69 years of age who underwent LASIK by the same surgeon between January 1999 and September 2005. Patients had manifest refractive spherical errors ranging from -10.5 to +6 diopters (D) and cylinder of up to 2.50 D. Methods: LASIK was performed with IntralLase femtosecond laser or Hansatome microkeratomes and VISX Star (S4 or S2; VISX Inc., Santa Clara, CA) or Baush & Lomb Technolas 217z (Zyoptix or PlanoScan; Bausch & Lomb, Claremont, CA) excimer lasers. There were 511 myopic eyes (spherical equivalent [SE1, -5.03 +/- 2.02 D) and 199 hyperopic eyes (SE, +2.21 +/- 1.21 D). Patients were divided into 3 groups: group 1 (40 to 49 years old; n = 359 eyes), group 2 (50 to 59 years old; n = 293 eyes), and group 3 (60 to 69 years old; n = 58 eyes). Main Outcome Measures: Uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA), retreatment rates, safety, efficacy, and predictability. Results: The mean age of patients in groups 1, 2, and 3 was 45, 53, and 63 years, respectively. With increasing age, there was a trend toward higher retreatment rates and more myopic end points. Safety, efficacy, and predictability were comparable between all groups. At the final follow-up (mean +/- standard deviation, 10.4 +/- 7.4 months), 80% to 100% of eyes had 20/30 or better UCVA and 81% to 90% were within +/- 1.00 D. No eyes lost more than 2 lines of BSCVA, and only 9 eyes (1.3%) lost 2 lines. Subgroup analysis of eyes with a follow-up of 12 months or more was performed. The results were compared with those with shorter follow-up. Both subgroups had comparable outcomes; the duration of follow-up did not affect the visual outcomes. Conclusions: Despite a trend toward worse final BSCVA and higher retreatment rates in older patients, a greater risk of visual loss after LASIK was not observed. LASIK for myopia and hyperopia has reasonable safety, efficacy, and predictability profiles in the 40- to 69-year-old presbyopic population. C1 Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu RI de la Cruz, Jose/A-1994-2010 FU NEI NIH HHS [EY10101] NR 24 TC 15 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2007 VL 114 IS 7 BP 1303 EP 1310 DI 10.1016/j.ophtha.2006.10.026 PG 8 WC Ophthalmology SC Ophthalmology GA 184GS UT WOS:000247629700011 PM 17382397 ER PT J AU Sonel, AF Shalaby, A Mcconnell, JP Czarnecki, T Hogen, S Zahid, M Amidi, M AF Sonel, Ali F. Shalaby, Alaa Mcconnell, Joseph P. Czarnecki, Tammy Hogen, Scott Zahid, Maliha Amidi, Morteza TI Detectable troponin levels predict poor prognosis in patients with left ventricular dysfunction undergoing internal defibrillator implantation SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; troponins; risk stratification; cardiomyopathy ID CONGESTIVE-HEART-FAILURE; CARDIOVERTER-DEFIBRILLATOR; RISK STRATIFICATION; COST-EFFECTIVENESS; SUDDEN-DEATH; MYOCARDIAL DAMAGE; INJURY; AMIODARONE; PREVENTION; MARKERS AB Introduction: Troponin levels have been demonstrated to predict mortality in patients with cardiomyopathy. Implantable cardiac defibrillator (ICD) devices have been demonstrated to improve survival. It is not clear if ICDs would mitigate the negative outcome predicted by elevated troponin levels. Methods: We collected baseline blood samples for troponin T (TnT) and creatinine kinase-MB fraction in consecutive patients immediately before successful pectoral transvenous ICD implant. Patients were followed for total mortality. For analysis, patients were grouped by TnT detectablility (>= 0.01 ng/mL). Results: Fifty-two men, aged 68 +/- 10 years, were studied. Mean ejection fraction was 29 +/- 12% and 65% had ischemic cardiomyopathy. Follow-up duration was 17 8 months. None of the patients had abnormal creatinine kinase-MB fraction levels (1.7 +/- 1.1 ng/mL). There were 37 patients with no detectable TnT (Group I) and 15 with detectable TnT (Group 11). There was no difference between the two groups in terms of age (68 vs 69, P = NS), ejection fraction (30 vs 29 %, P = NS), or proportion of patients with ischemic cardiomyopathy (68 vs 60%, P = NS). During follow-up 16 (31 %) patients died. Patients in group I had mortality of 16% (6/37) compared to 67% mortality (10/15, P < 0.001) in group II. On multivariate analysis, detectable TnT remained an independent predictor of mortality (HR 4.5, Cl 1.4-14.25, P = 0.01). Conclusion: In a cohort of patients with cardiomyopathy undergoing ICD implantation for standard clinical indications, presence of detectable TnT was associated with high mortality despite ICD implantation. TnT obtained before ICD implantation may be useful for risk stratification. C1 VA Pittsburgh Healthcare Syst, Univ Dr Div, Dept Cardiol, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. Mayo Clin, Rochester, MN USA. RP Shalaby, A (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr Div, Dept Cardiol, 111C-U, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@med.va.gov NR 31 TC 7 Z9 7 U1 0 U2 0 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 JUL PY 2007 VL 30 IS 7 BP 839 EP 844 DI 10.1111/j.1540-8159.2007.00770.x PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 187OE UT WOS:000247856800003 PM 17584264 ER EF