FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Zhang, C Solomon, CG Hu, FB AF Zhang, C. Solomon, C. G. Hu, F. B. TI A prospective study of pre-pregnancy abdominal adiposity and the risk of gestational diabetes SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Zhang, C.; Solomon, C. G.; Hu, F. B.] NICHD, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S29 EP S29 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200116 ER PT J AU Sabri, M Di Lorenzo, C Henderson, W Thompson, W Barksdale, E Khan, S AF Sabri, Mahmoud Di Lorenzo, Carlo Henderson, Wendy Thompson, William Barksdale, Edward, Jr. Khan, Seema TI Colon cleansing with oral sodium phosphate in adolescents: Dose, efficacy, acceptability, and safety SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SUPERIOR COLONOSCOPY PREPARATION; POLYETHYLENE-GLYCOL; BOWEL PREPARATION; LAVAGE SOLUTION; CHILDREN; VOLUME; TRIAL; HYPOCALCEMIA; FLEET(R) AB BACKGROUND AND AIMS: Standardized bowel preparation in children and adolescents has not been established. Our aim was to compare two bowel preparation regimens and determine which was more effective, acceptable, and safer for children undergoing colonoscopy. METHODS: We compared the efficacy and acceptability of a 1-day regimen with oral sodium phosphate solution (NaP solution) (1 mL/kg/day, maximum 90 mL in two divided doses; regimen A) to our standard 3-day regimen magnesium citrate (4 mL/kg/day x 3 days, maximum 237 mL, followed by an enema the morning of colonoscopy; regimen B). After informed consent was obtained, 48 children were randomized (N = 25, 23, respectively). Weight, electrolytes, calcium, phosphorus, and magnesium were measured at screening and the day of the colonoscopy. Questionnaires were given to assess acceptability and adverse events. Endoscopists rated the quality of bowel preparation on a 4-level scale from excellent to poor. RESULTS: Median age and weight at screening were 14 yr, 53 kg, and 15 yr, 51 kg in regimen A and B, respectively. No statistical significance was observed in electrolytes, phosphorus, or adverse events apart from higher nausea intensity in regimen A (P = 0.012). Bowel cleansing was similar between groups (71% excellent or good). Subjects were more willing to repeat regimen A than B (77% vs 32%, respectively, P < 0.006). All 10 subjects who received regimen A and had prior colonoscopies using regimen B, preferred regimen A. CONCLUSIONS: In a selected group of otherwise healthy children and adolescents over 10.5 yr and above 34 kg, 1-day oral NaP solution was more acceptable than 3-day magnesium citrate with an enema, and both regimens were found to be safe and efficacious. C1 [Sabri, Mahmoud] Geisinger Med Ctr, Div Pediat Gastroenterol, Danville, PA 17822 USA. [Di Lorenzo, Carlo] Columbus Childrens Hosp, Columbus, OH USA. [Henderson, Wendy] NIH, Bethesda, MD 20892 USA. [Thompson, William] Med Coll Georgia, Augusta, GA 30912 USA. [Barksdale, Edward, Jr.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Khan, Seema] Alfred I duPont Hosp Children, Nemours Childrens Clin, Wilmington, DE USA. RP Sabri, M (reprint author), Geisinger Med Ctr, Div Pediat Gastroenterol, 100 N Acad Ave, Danville, PA 17822 USA. OI Henderson, Wendy/0000-0003-3924-7118 FU NCRR NIH HHS [M01RR00084] NR 28 TC 18 Z9 18 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2008 VL 103 IS 6 BP 1533 EP 1539 DI 10.1111/j.1572-0241.2008.01806.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 311OY UT WOS:000256610700034 PM 18510625 ER PT J AU Aliyu, ZY Gordeuk, V Sachdev, V Babadoko, A Mamman, AI Akpanpe, P Attah, E Suleiman, Y Aliyu, N Yusuf, J Mendelsohn, L Kato, GJ Gladwin, MT AF Aliyu, Zakari Y. Gordeuk, Victor Sachdev, Vandana Babadoko, Aliyu Mamman, Aisha I. Akpanpe, Peter Attah, Ester Suleiman, Yusuf Aliyu, Nurudeen Yusuf, Jamilu Mendelsohn, Laurel Kato, Gregory J. Gladwin, Mark T. TI Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID NITRIC-OXIDE BIOAVAILABILITY; STANDARDS COMMITTEE; OF-ECHOCARDIOGRAPHY; DEATH; RECOMMENDATIONS; QUANTIFICATION; THALASSEMIA; HEMOGLOBIN; MANAGEMENT; MORTALITY AB Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in sub-Saharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naive Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity >= 2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were >35 years. Tricuspid regurgitant jet velocity was >= 2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin (P = 0.002), blood urea nitrogen (P = 0.019) and lactate dehydrogenase concentrations (P = 0.026) and with inability to walk >300 m in 6 min (P = 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations (P <= 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged. C1 [Aliyu, Zakari Y.; Gordeuk, Victor] Howard Univ, Dept Med, Washington, DC 20060 USA. [Aliyu, Zakari Y.; Gordeuk, Victor] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA. [Aliyu, Zakari Y.; Mendelsohn, Laurel; Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Babadoko, Aliyu; Mamman, Aisha I.; Akpanpe, Peter; Attah, Ester; Suleiman, Yusuf; Aliyu, Nurudeen; Yusuf, Jamilu] Ahmadu Bello Univ Hosp, Shika Zaria, Nigeria. RP Aliyu, ZY (reprint author), Howard Univ, Dept Med, 2041 Geprgia Ave NW, Washington, DC 20060 USA. EM aliyuz@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [ZIA HL005075-04, ZIA HL005075-05]; NHLBI NIH HHS [1 R01 HL079912-03, 2 R25 HL003679-08, R01 HL079912, R25 HL003679] NR 23 TC 35 Z9 35 U1 0 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 JUN PY 2008 VL 83 IS 6 BP 485 EP 490 DI 10.1002/ajh.21162 PG 6 WC Hematology SC Hematology GA 305VD UT WOS:000256205000011 PM 18306362 ER PT J AU Arnaud-Lopez, L Usala, G Ceresini, G Mitchell, BD Pilia, MG Piras, MG Sestu, N Maschio, A Busonero, F Albai, G Dei, M Lai, S Mulas, A Crisponi, L Tanaka, T Bandinelli, S Guralnik, JM Loi, A Balaci, L Sole, G Prinzis, A Mariotti, S Shuldiner, AR Cao, A Schlessinger, D Uda, M Abecasis, GR Nagaraja, R Sanna, S Naitza, S AF Arnaud-Lopez, Lisette Usala, Gianluca Ceresini, Graziano Mitchell, Braxton D. Pilia, Maria Grazia Piras, Maria Grazia Sestu, Natascia Maschio, Andrea Busonero, Fabio Albai, Giuseppe Dei, Mariano Lai, Sandra Mulas, Antonella Crisponi, Laura Tanaka, Toshiko Bandinelli, Stefania Guralnik, Jack M. Loi, Angela Balaci, Lenuta Sole, Gabriella Prinzis, Alessia Mariotti, Stefano Shuldiner, Alan R. Cao, Antonio Schlessinger, David Uda, Manuela Abecasis, Goncalo R. Nagaraja, Ramaiah Sanna, Serena Naitza, Silvia TI Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OLD ORDER AMISH; CAMP-SPECIFIC PHOSPHODIESTERASE; GENOME-WIDE ASSOCIATION; THYROTROPIN RECEPTOR; FEEDBACK-REGULATION; HORMONE; LINKAGE; MUTATIONS; PITUITARY; DISEASE AB Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting similar to 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 mu IU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 x 10(-5)), GNAQ (rs10512065, p = 2.0 x 10(-4)), TG (rs2252696, p = 2.2 x 10(-3)), POU1F1 (rs1976324, p = 3.9 x 10(-3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction. C1 [Usala, Gianluca; Pilia, Maria Grazia; Piras, Maria Grazia; Sestu, Natascia; Maschio, Andrea; Busonero, Fabio; Albai, Giuseppe; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Crisponi, Laura; Loi, Angela; Balaci, Lenuta; Sole, Gabriella; Cao, Antonio; Uda, Manuela; Sanna, Serena; Naitza, Silvia] CNR, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy. [Ceresini, Graziano] Univ Parma, Dept Internal Med, Sect Geriatr, I-43100 Parma, Italy. [Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Tanaka, Toshiko] NIA, Clin Res Branch, Baltimore, MD 21225 USA. [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, I-50125 Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Prinzis, Alessia; Mariotti, Stefano] Univ Cagliari, Dept Med Sci M Aresu, I-09042 Cagliari, Italy. [Shuldiner, Alan R.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21201 USA. [Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Arnaud-Lopez, Lisette; Schlessinger, David; Nagaraja, Ramaiah] NIA, Genet Lab, Baltimore, MD 21224 USA. RP Naitza, S (reprint author), CNR, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy. EM silvia.naitza@inn.cnr.it RI Abecasis, Goncalo/B-7840-2010; Sole, Gabriella /I-4820-2013; Naitza, Silvia/D-5620-2017 OI Sole, Gabriella /0000-0001-5292-5038; FU Intramural NIH HHS; NCRR NIH HHS [M01 RR 000052, M01 RR000052, M01 RR016500]; NHGRI NIH HHS [HG002651, R01 HG002651]; NHLBI NIH HHS [HL084729, U01 HL072515, U01 HL084729, U01 HL72515]; NIA NIH HHS [N01-AG-1-2109, N01-AG-821336, N01-AG-916413, R01 AG018728, R01 AG18728]; NIMHD NIH HHS [263 MD 821336, 263 MD 916413, R01 MD009164]; PHS HHS [263-MA-410953] NR 47 TC 75 Z9 77 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2008 VL 82 IS 6 BP 1270 EP 1280 DI 10.1016/j.ajhg.2008.04.019 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 312CP UT WOS:000256647000005 PM 18514160 ER PT J AU Beydoun, MA Beason-Held, LL AF Beydoun, May A. Beason-Held, Lori L. TI Does hypertension interact with body weight to impact cognitive function in the elderly?: Emerging evidence SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material ID MASS INDEX; DEMENTIA; RISK C1 [Beydoun, May A.; Beason-Held, Lori L.] NIA, Lab Personal & Cognit, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Beason-Held, LL (reprint author), NIA, Lab Personal & Cognit, Natl Inst Hlth, Baltimore, MD 21224 USA. EM heldlo@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000191-11] NR 6 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2008 VL 21 IS 6 BP 603 EP 603 DI 10.1038/ajh.2008.181 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 300RB UT WOS:000255841800004 PM 18500326 ER PT J AU Brown, JA AF Brown, J. A. TI An internet database for the classification and dissemination of information about hazardous chemicals and occupational diseases SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational disease prevention; occupational disease surveillance; public health informatics; decision support systems ID PUBLIC-HEALTH SURVEILLANCE; PHYSICIAN RECOGNITION; JOB TASKS; TECHNOLOGY; EXPOSURES; EVENTS AB Background The amount of information about hazardous agents in the workplace exceeds the capacity of human memory. There is a need to accurately represent or map this scientific knowledge for digital storage and retrieval. Methods A relational database of hazardous chemicals and occupational diseases was constructed by first collecting and sifting through the large volume of information. The information was indexed with a controlled vocabulary and documented with references to the scientific literature. Results The evolving database is available on the website of the National Library of Medicine. It enables users to browse categories and query by pick lists. Users can drill down to find specific information that may be useful for intervention and prevention. Conclusions The large amount of information needed to support decisions concerning occupational exposures and diseases can be distilled, classified, and summarized in a relational database and disseminated by means of the World Wide Web to assist in the prevention of work-related diseases. C1 [Brown, J. A.] Natl Lib Med, Specialized Informat Serv, Bethesda, MD USA. [Brown, J. A.] US Dept Labor, Enerygy Employees Occupat Illness Compensat Progr, Washington, DC USA. RP Brown, JA (reprint author), 5426 Orca Pl NE, Tacoma, WA USA. EM brownjay@haz-map.com NR 69 TC 3 Z9 3 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 2008 VL 51 IS 6 BP 428 EP 435 DI 10.1002/ajim.20578 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 303MU UT WOS:000256045400005 PM 18335440 ER PT J AU Brotman, RM Ghanem, KG Klebanoff, MA Taha, TE Scharfstein, DO Zenilman, JM AF Brotman, Rebecca M. Ghanem, Khalil G. Klebanoff, Mark A. Taha, Taha E. Scharfstein, Daniel O. Zenilman, Jonathan M. TI The effect of vaginal douching cessation on bacterial vaginosis: a pilot study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 17th Meeting of the International-Society-for-Sexually-Transmitted-Diseases-Research CY JUL 29-AUG 01, 2007 CL Seattle, WA SP Int Soc Sexually Transmitted Dis Res DE bacterial vaginosis; intravaginal cleansing; intravaginal washing; vaginal douching ID PELVIC INFLAMMATORY DISEASE; CHLAMYDIA-TRACHOMATIS INFECTION; RISK-FACTOR; ECTOPIC PREGNANCY; MENSTRUAL-CYCLE; UNITED-STATES; WOMEN; FLORA; MICROFLORA; ASSOCIATION AB OBJECTIVE: The objective of the study was to evaluate the risk for bacterial vaginosis (BV) in a douching cessation trial. STUDY DESIGN: Thirty-nine reproductive-age women who reported use of douche products were enrolled into a 20-week study consisting of a 4 week douching observation (phase I) followed by 12-weeks of douching cessation (phase II). In phase III, participants then chose to resume douching or continue cessation for the remaining 4 weeks. Self-collected vaginal samples were obtained twice weekly in the first 16 weeks, and 1 sample was collected during week 20 (1107 samples total). BV was diagnosed by Nugent score of 7 or greater. Conditional logistic regression was used to evaluate douching cessation on the risk of BV. RESULTS: The adjusted odds ratio (aOR) for BV in the douching cessation phase, as compared with the douching-observation phase was 0.76 (95% confidence interval [CI], 0.33 to 1.76). Among women who reported their primary reason for douching was to cleanse after menstruation, BV was significantly reduced in douching cessation (aOR: 0.23; 95% CI, 0.12 to 0.44). CONCLUSION: Vaginal douching cessation may reduce the risk for BV in a subset of women. C1 [Brotman, Rebecca M.; Taha, Taha E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Scharfstein, Daniel O.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Ghanem, Khalil G.; Zenilman, Jonathan M.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Brotman, Rebecca M.; Klebanoff, Mark A.] NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. RP Brotman, RM (reprint author), Johns Hopkins Bayview Med Ctr, 4940 Eastern Ave,B-3 N, Baltimore, MD 21224 USA. EM rbrotman@jhsph.edu RI Brotman, Rebecca/H-5442-2011; OI Brotman, Rebecca/0000-0001-8762-6214 NR 50 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2008 VL 198 IS 6 AR 628.e1 DI 10.1016/j.ajog.2007.11.043 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 309FM UT WOS:000256446100005 ER PT J AU Chen, BA Reeves, MF Creinin, MD Gilles, JM Barnhart, K Westhoff, C Zhang, J AF Chen, Beatrice A. Reeves, Matthew F. Creinin, Mitchell D. Gilles, Jerry M. Barnhart, Kurt Westhoff, Carolyn Zhang, Jun CA Natl Inst Child Hlth & Human Dev M TI Misoprostol for treatment of early pregnancy failure in women with previous uterine surgery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean delivery; early pregnancy failure; miscarriage; misoprostol; myomectomy ID SPONTANEOUS RUPTURE; 1ST TRIMESTER; 1ST-TRIMESTER; UTERUS; TERMINATION; MYOMECTOMY AB OBJECTIVE: Misoprostol use in early pregnancy may incur a risk of uterine rupture in women with previous uterine surgery. STUDY DESIGN: We analyzed 488 women who received misoprostol 800 mu g vaginally in a study that evaluated medical and surgical management of early pregnancy failure. Subjects received a repeat misoprostol dose if expulsion was not confirmed 2 days after treatment. We compared efficacy, acceptability, and safety in subjects with a history (n = 78 women) or absence (n = 410 women) of uterine surgery, defined as cesarean delivery or myomectomy. RESULTS: Expulsion rates after a single misoprostol dose (69% vs 72%; P = .64) and overall success at 30 days (82% vs 85%; P = .50) were comparable. Pain, bleeding, complications, and acceptability did not differ. No uterine ruptures occurred (95% CI, 0, 3.8%). CONCLUSION: Misoprostol treatment for early pregnancy failure had similar success, acceptability, and complications in women with and without previous uterine surgery. C1 [Chen, Beatrice A.; Reeves, Matthew F.; Creinin, Mitchell D.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Chen, Beatrice A.; Reeves, Matthew F.; Creinin, Mitchell D.] Magee Womens Res Inst, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Gilles, Jerry M.] Univ Miami, Dept Obstet & Gynecol, Miami, FL 33101 USA. [Barnhart, Kurt] Univ Penn, Med Ctr, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Barnhart, Kurt] Univ Penn, Med Ctr, Ctr Clin Epidemiol, Philadelphia, PA 19104 USA. [Westhoff, Carolyn] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Zhang, Jun] NIH, NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chen, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. OI Reeves, Matthew/0000-0001-7749-7447 FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [MO1RR000056, M01 RR000056-45, M01 RR000056]; NICHD NIH HHS [N01-HD-1-3321, N01 HD013322] NR 19 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2008 VL 198 IS 6 AR 626.e1 DI 10.1016/j.ajog.2007.11.045 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 309FM UT WOS:000256446100004 PM 18279821 ER PT J AU Venneti, S Bonneh-Barkay, D Lopresti, BJ Bissel, SJ Wang, G Mathis, CA Piatak, M Lifson, JD Nyaundi, JO Murphey-Corb, M Wiley, CA AF Venneti, Sriram Bonneh-Barkay, Dafna Lopresti, Brian J. Bissel, Stephanie J. Wang, Guoji Mathis, Chester A. Piatak, Michael, Jr. Lifson, Jeffrey D. Nyaundi, Julia O. Murphey-Corb, Michael Wiley, Clayton A. TI Longitudinal in vivo positron emission tomography imaging of infected and activated brain macrophages in a macaque model of human immunodeficiency virus encephalitis correlates with central and peripheral markers of encephalitis and areas of synaptic degeneration SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; HIV-ASSOCIATED DEMENTIA; BENZODIAZEPINE-RECEPTOR; ANTIRETROVIRAL THERAPY; CEREBROSPINAL-FLUID; VIRAL LOAD; HAART ERA; COGNITIVE IMPAIRMENT; RHESUS-MONKEYS AB Human immunodeficiency virus encephalitis is characterized by infiltration of the brain with infected and activated macrophages; however, it is not known why disease occurs after variable lengths of infection in 25% of immunosuppressed acquired immune deficiency syndrome patients. We determined in vivo correlates (in peripheral blood and the central nervous system) for the development and progression of lentiviral encephalitis by longitudinally following infected and activated macrophages; in the brain using positron emission tomography (PET). Using human postmortem brain tissues from both lentivirus-infected encephalitic patients and cell culture systems, we showed that the PET ligand [H-3](R)-PK11195 bound specifically to virus-infected and activated macrophages. We longitudinally imaged infected and activated brain macrophages in a cohort of macaques infected with simian immunodeficiency virus using [C-11](R)-PK11195. [C-11](R)-PK11195 retention in vivo in the brain correlated with viral burden in the brain and cerebrospinal fluid, and with regions of both presynaptic and postsynaptic damage. Finally, longitudinal changes in [C-11](R)-PK11195 retention in the brain in vivo correlated with changes in circulating monocytes as well as in both natural killer and memory CD4(+) T cells in the periphery. our results suggest that development and progression of simian immunodeficiency virus encephalitis in vivo correlates with changes in specific cell subtypes in the periphery. A combination of PET imaging and the assessment of these peripheral immune parameters may facilitate longitudinal assessment of lentiviral encephalitis in living patients as well as evaluation of therapeutic efficacies. C1 [Venneti, Sriram; Bonneh-Barkay, Dafna; Bissel, Stephanie J.; Wang, Guoji; Wiley, Clayton A.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Lopresti, Brian J.; Mathis, Chester A.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Nyaundi, Julia O.; Murphey-Corb, Michael] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] Sci Applicat Int Corp, Natl Canc Inst Frederick, Lab Retroviral Pathogenesis, AIDS Vaccine Program, Frederick, MD USA. RP Wiley, CA (reprint author), Presbyterian Univ Hosp, Div Neuropathol, 200 Lothrop St,A515, Pittsburgh, PA 15213 USA. EM wiley1l@pitt.edu RI Mathis, Chester/A-8607-2009; Lopresti, Brian/O-2465-2016 OI Lopresti, Brian/0000-0002-0595-0203 FU NIMH NIH HHS [K24 MH001717, R01 MH071151-04S1, K24 MH01717, K24 MH001717-09, R01 MH071151] NR 55 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2008 VL 172 IS 6 BP 1603 EP 1616 DI 10.2353/ajpath.2008.070967 PG 14 WC Pathology SC Pathology GA 307NY UT WOS:000256326800017 PM 18467697 ER PT J AU Woodard, GE Salido, GM Rosado, JA AF Woodard, Geoffrey E. Salido, Gines M. Rosado, Juan A. TI Enhanced exocytotic-like insertion of Orai1 into the plasma membrane upon intracellular Ca2+ store depletion SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Orai1; synaptosomal-associated protein-25; Ca2+ entry ID HUMAN PLATELETS; CALCIUM-ENTRY; CRAC CHANNEL; HEK-293 CELLS; STIM1; ACTIVATION; SNAP-25; INFLUX; PROTEINS; SUBUNIT AB Ca+ release-activated Ca2+ (CRAC) channels are activated when free Ca2+ concentration in the intracellular stores is substantially reduced and mediate sustained Ca2+ entry. Recent studies have identified Orai1 as a CRAC channel subunit. Here we demonstrate that passive Ca2+ store depletion using the inhibitor of the sarcoendoplasmic reticulum Ca2+-ATPase, thapsigargin (TG), enhances the surface expression of Orai1, a process that depends on rises in cytosolic free Ca2+ concentration, as demonstrated in cells loaded with dimethyl BAPTA, an intracellular Ca2+ chelator that prevented TG-evoked cytosolic free Ca2+ concentration elevation. Similar results were observed with a low concentration of carbachol. Cleavage of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor, synaptosomal-assiciated protein-25 (SNAP-25), with botulinum neurotoxin A impaired TG-induced increase in the surface expression of Orai1. In addition, SNAP-25 cleaving by botulinum neurotoxin A reduces the maintenance but not the initial stages of store-operated Ca2+ entry. In aggregate, these findings demonstrate that store depletion enhances Orai1 plasma membrane expression in an exocytotic manner that involves SNAP-25, a process that contributes to store-dependent Ca2+ entry. C1 [Salido, Gines M.; Rosado, Juan A.] Univ Extremadura, Dept Physiol, Cell Physiol Res Grp, Caceres 10071, Spain. [Woodard, Geoffrey E.] NIDDK, NIH, Bethesda, MD USA. RP Rosado, JA (reprint author), Univ Extremadura, Dept Physiol, Cell Physiol Res Grp, Caceres 10071, Spain. EM jarosado@unex.es RI Woodard, Geoffrey/A-8608-2009; Salido, Gines/A-4292-2009; rosado, juan/H-3488-2015 OI Salido, Gines/0000-0002-8687-2445; rosado, juan/0000-0002-9749-2325 NR 34 TC 21 Z9 21 U1 0 U2 2 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 JUN PY 2008 VL 294 IS 6 BP C1323 EP C1331 DI 10.1152/ajpcell.00071.2008 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 311BL UT WOS:000256574900006 PM 18400989 ER PT J AU Csiszar, A Labinskyy, N Podlutsky, A Kaminski, PM Wolin, MS Zhang, CH Mukhopadhyay, P Pacher, P Hu, FR de Cabo, R Ballabh, P Ungvari, Z AF Csiszar, Anna Labinskyy, Nazar Podlutsky, Andrej Kaminski, Pawel M. Wolin, Michael S. Zhang, Cuihua Mukhopadhyay, Partha Pacher, Pal Hu, Furong de Cabo, Rafael Ballabh, Praveen Ungvari, Zoltan TI Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE tobacco; polyphenol; stroke; inflammation; apoptosis; vascular aging; sirtuin 1 ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; MITOCHONDRIAL SUPEROXIDE-PRODUCTION; ENDOTHELIUM-DEPENDENT DILATION; ELECTRON-SPIN-RESONANCE; DNA-DAMAGE; CORONARY-ARTERIES; NAD(P)H OXIDASE; LIFE-SPAN; CALORIC RESTRICTION AB The dietary polyphenolic compound resveratrol, by activating the protein deacetylase enzyme silent information regulator 2/sirtuin 1 (SIRT1), prolongs life span in evolutionarily distant organisms and may mimic the cytoprotective effects of dietary restriction. The present study was designed to elucidate the effects of resveratrol on cigarette smoke-induced vascular oxidative stress and inflammation, which is a clinically highly relevant model of accelerated vascular aging. Cigarette smoke exposure of rats impaired the acetylcholine-induced relaxation of carotid arteries, which could be prevented by resveratrol treatment. Smoking and in vitro treatment with cigarette smoke extract (CSE) increased reactive oxygen species production in rat arteries and cultured coronary arterial endothelial cells (CAECs), respectively, which was attenuated by resveratrol treatment. The smoking-induced upregulation of inflammatory markers (ICAM-1, inducible nitric oxide synthase, IL-6, and TNF-alpha) in rat arteries was also abrogated by resveratrol treatment. Resveratrol also inhibited CSE-induced NF-kappa B activation and inflammatory gene expression in CAECs. In CAECs, the aforementioned protective effects of resveratrol were abolished by knockdown of SIRT1, whereas the overexpression of SIRT1 mimicked the effects of resveratrol. Resveratrol treatment of rats protected aortic endothelial cells against cigarette smoking-induced apoptotic cell death. Resveratrol also exerted antiapoptotic effects in CSE-treated CAECs, which could be abrogated by knockdown of SIRT1. Resveratrol treatment also attenuated CSE-induced DNA damage in CAECs (comet assay). Thus resveratrol and SIRT1 exert antioxidant, anti-inflammatory, and antiapoptotic effects, which protect the endothelial cells against the adverse effects of cigarette smoking-induced oxidative stress. The vasoprotective effects of resveratrol will likely contribute to its anti-aging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging. C1 [Csiszar, Anna; Labinskyy, Nazar; Kaminski, Pawel M.; Wolin, Michael S.; Ungvari, Zoltan] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. [Hu, Furong; Ballabh, Praveen] New York Med Coll, Dept Cell Biol, Valhalla, NY 10595 USA. [Podlutsky, Andrej] Univ Texas San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Zhang, Cuihua] Univ Missouri, Dalton Cardiovasc Res Ctr, Dept Internal Med, Columbia, MO USA. [Zhang, Cuihua] Univ Missouri, Dalton Cardiovasc Res Ctr, Dept Med Pharmacol, Columbia, MO USA. [Zhang, Cuihua] Univ Missouri, Dalton Cardiovasc Res Ctr, Dept Physiol, Columbia, MO USA. [Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Ungvari, Z (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. EM zoltan_ungvari@nymc.edu RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Podlutsky, Andrej/F-5421-2015; de Cabo, Rafael/J-5230-2016; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999]; NHLBI NIH HHS [R01 HL066331-07, HL-077256, HL-43023, P01 HL043023, P01 HL043023-16A19002, P01 HL043023-17, P01 HL043023-170002, P01 HL043023-179002, R01 HL031069, R01 HL031069-23, R01 HL066331, R01 HL077256, R01 HL077256-01A2] NR 73 TC 156 Z9 162 U1 2 U2 16 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 JUN PY 2008 VL 294 IS 6 BP H2721 EP H2735 DI 10.1152/ajpheart.00235.2008 PG 15 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 309YY UT WOS:000256497300037 PM 18424637 ER PT J AU Leatherbury, L Yu, Q Chatterjee, B Walker, DL Yu, Z Tian, X Lo, CW AF Leatherbury, L. Yu, Q. Chatterjee, B. Walker, D. L. Yu, Z. Tian, X. Lo, C. W. TI A novel mouse model of X-linked cardiac hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE echocardiography; X-linked cardiomyopathy; hypertrophic cardiomyopathy; ultrasound ID ACYL-COA DEHYDROGENASE; II TYPE-2 RECEPTOR; BARTH-SYNDROME; CARDIOLIPIN METABOLISM; SUDDEN-DEATH; IN-VIVO; CARDIOMYOPATHY; GENE; MICE; MUTATIONS AB We recovered a novel mouse mutant exhibiting neonatal lethality associated with severe fetal cardiac hypertrophy and with some adult mice dying suddenly with left ventricular hypertrophic cardiomyopathy. Using Doppler echocardiography, we screened surviving adult mice in this mutant line for cardiac hypertrophy. Cardiac dimensions were obtained either from two-dimensional images collected using a novel ECG-gated ultra-high-frequency ultrasound system or by traditional M-mode imaging on a clinical ultrasound system. These analyses identified, among the littermates, two populations of mice: those with apparent cardiac hypertrophy with hypercontractile function characterized by ejection fraction of 75-80%, and normal littermates with ejection fraction of 53-55%. Analysis of the ECG-gated two-dimensional cines indicated that the hypertrophy was of the nonobstructive type. Further analysis of heart-to-body weight ratio confirmed the ultrasound diagnosis of left ventricular hypertrophic cardiomyopathy. Histopathology showed increased ventricular wall thickness, enlarged myocyte size, and mild myofiber disarray. Ultrastructural analysis by electron microscopy revealed mitochondria hyperproliferation and dilated sarcoplasmic reticulum. Genome scanning using microsatellite DNA markers mapped the mutation to the X chromosome. DNA sequencing showed no mutations in the coding regions of several candidate genes on the X chromosome, including several known to be associated with left ventricular hypertrophic cardiomyopathy. These findings suggest that this mouse line may harbor a mutation in a novel gene causing X-linked cardiomyopathy. C1 [Leatherbury, L.; Yu, Q.; Chatterjee, B.; Walker, D. L.; Lo, C. W.] NHLBI, LDB, NIH, Bethesda, MD 20892 USA. [Tian, X.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Leatherbury, L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Leatherbury, L (reprint author), NHLBI, LDB, NIH, 10 Ctr MSC 15836 6C103, Bethesda, MD 20892 USA. EM lleather@cnmc.org FU NHLBI NIH HHS [Z01-HL005701] NR 46 TC 5 Z9 6 U1 1 U2 2 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 JUN PY 2008 VL 294 IS 6 BP H2701 EP H2711 DI 10.1152/ajpheart.00160.2007 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 309YY UT WOS:000256497300035 PM 18424640 ER PT J AU Shivakumar, K Sollott, SJ Sangeetha, M Sapna, S Ziman, B Wang, S Lakatta, EG AF Shivakumar, K. Sollott, S. J. Sangeetha, M. Sapna, S. Ziman, B. Wang, S. Lakatta, E. G. TI Paracrine effects of hypoxic fibroblast-derived factors on the MPT-ROS threshold and viability of adult rat cardiac myocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE mitochondrial permeability transition-reactive oxygen pecies threshold; cardiac myocyte viability; cardiac fibroblasts; hypoxia; fibroblast-conditioned edium; fibroblast proliferation; apoptosis; necrosis; tumor necrosis factor-alpha ID MITOCHONDRIAL PERMEABILITY TRANSITION; TUMOR-NECROSIS-FACTOR; CELL-DEATH; GROWTH-FACTOR; VENTRICULAR MYOCYTES; ANGIOTENSIN-II; DNA-SYNTHESIS; HEART; NONMYOCYTES; REPERFUSION AB Cardiac fibroblasts contribute to multiple aspects of myocardial function and pathophysiology. The pathogenetic relevance of cytokine production by these cells under hypoxia, however, remains unexplored. With the use of an in vitro cell culture model, this study evaluated cytokine production by hypoxic cardiac fibroblasts and examined two distinct effects of hypoxic fibroblast-conditioned medium (HFCM) on cardiac myocytes and fibroblasts. Hypoxia caused a marked increase in the production of tumor necrosis factor (TNF)-alpha by cardiac fibroblasts. HFCM significantly enhanced the susceptibility of cardiac myocytes to reactive oxygen species (ROS)-induced mitochondrial permeability transition (MPT), determined by high-precision confocal line-scan imaging following controlled, photoexcitation-induced ROS production within individual mitochondria. Furthermore, exposure of cardiac myocytes to HFCM for 5 h led to loss of viability, as evidenced by change in morphology and annexin staining. HFCM also decreased DNA synthesis in cardiac fibroblasts. Normoxic fibroblast-conditioned medium spiked with TNF-alpha at 200 pg/ml, a concentration comparable to that in HFCM, promoted loss of myocyte viability and decreased DNA synthesis in cardiac fibroblasts. These effects of HFCM are similar to the reported effects of hypoxia per se on these cell types, showing that hypoxic fibroblast-derived factors may amplify the distinct effects of hypoxia on cardiac cells. Importantly, because both hypoxia and oxidant stress prevail in a setting of ischemia and reperfusion, the effects of soluble factors from hypoxic fibroblasts on the MPT-ROS threshold and viability of myocytes may represent a novel paracrine mechanism that could exacerbate ischemia-reperfusion injury to cardiomyocytes. C1 [Shivakumar, K.; Sangeetha, M.; Sapna, S.] Sree Chitra Tirunal Inst Med Sci & Technol, Div Cellular & Mol Cardiol, Trivandrum 695011, Kerala, India. [Sollott, S. J.; Ziman, B.; Wang, S.; Lakatta, E. G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Shivakumar, K (reprint author), Sree Chitra Tirunal Inst Med Sci & Technol, Div Cellular & Mol Cardiol, Trivandrum 695011, Kerala, India. EM shivak@sctimst.ac.in NR 32 TC 15 Z9 15 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 JUN PY 2008 VL 294 IS 6 BP H2653 EP H2658 DI 10.1152/ajpheart.91443.2007 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 309YY UT WOS:000256497300029 PM 18408121 ER PT J AU Atienza, AA King, AC Oliveira, BM Ahn, DK Gardner, CD AF Atienza, Audie A. King, Abby C. Oliveira, Brian M. Ahn, David K. Gardner, Christopher D. TI Using hand-held computer technologies to improve dietary intake SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID WHOLE-GRAIN CONSUMPTION; PHYSICAL-ACTIVITY; VEGETABLE CONSUMPTION; HISTORY QUESTIONNAIRE; WEIGHT-LOSS; NUTRITION; PROGRAM; HEALTH; CANCER; FRUIT AB Background: Portable hand-held information technology offers much promise not only in assessing dietary intake in the real world, but also in providing dietary feedback to individuals. However, stringent research designs have not been employed to examine whether it can be effective in modifying dietary behaviors. The purpose of this pilot study was to evaluate the efficacy of a hand-held computer (i.e., personal digital assistant [PDA]) for increasing vegetable and whole-grain intake over 8 weeks in mid-life and older adults, using a randomized study design. Methods: Twenty-seven healthy adults aged 50 were randomized and completed the 8-week study. Intervention participants received an instructional session and a PDA programmed to monitor their vegetable and whole-grain intake levels twice per day and to provide daily individualized feedback, goal-setting, and support. Controls received standard, age-appropriate, written nutritional education materials. Dietary intake was assessed via the Block Food Frequency Questionnaire at baseline and 8 weeks. Results: Relative to controls, intervention participants reported significantly greater increases in vegetable servings (1.5-2.5 servings/day; p=0.02), as well as a trend toward greater intake of dietary fiber from grains (3.7-4.5 servings/day; p=0.10). Conclusions: This study's findings provide preliminary evidence that using portable hand-held technology to provide daily individualized feedback OD dietary behavior in the real world can increase the dietary intake of healthy food groups. C1 [Atienza, Audie A.] NCI, NIH, Div Canc Control & Populat Sci, Behav Res Program,Hlth Promot Res Branch, Bethesda, MD 20892 USA. [King, Abby C.; Oliveira, Brian M.; Ahn, David K.; Gardner, Christopher D.] Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Atienza, AA (reprint author), NCI, NIH, Div Canc Control & Populat Sci, Behav Res Program,Hlth Promot Res Branch, 6130 Execut Blvd,EPN 4082, Bethesda, MD 20892 USA. EM AtienzaA@mail.nih.gov FU PHS HHS [5T32H107034] NR 42 TC 30 Z9 31 U1 1 U2 7 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 JUN PY 2008 VL 34 IS 6 BP 514 EP 518 DI 10.1016/j.amepre.2008.01.034 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 305HS UT WOS:000256169500009 PM 18471588 ER PT J AU Shaikh, AR Yaroch, AL Nebeling, L Yeh, MC Resnicow, K AF Shaikh, Abdul R. Yaroch, Amy L. Nebeling, Linda Yeh, Ming-Chin Resnicow, Ken TI Psychosocial predictors of fruit and vegetable consumption in adults - A review of the literature SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID SELF-DETERMINATION THEORY; DIETARY CHANGE; NUTRITION INTERVENTION; TRANSTHEORETICAL MODEL; CANCER PREVENTION; PHYSICAL-ACTIVITY; SUPPORTING AUTONOMY; MEDIATING VARIABLES; PLANNED BEHAVIOR; UNITED-STATES AB Background: Adequate fruit and vegetable intake has been found to promote health and reduce the risk of several cancers and chronic diseases. Understanding the psychological determinants of fruit and vegetable intake is needed to design effective intervention programs. Methods: Papers published in English from 1994 to 2006 that described the relationship between psychosocial predictors and fruit and vegetable intake in adults were reviewed. Studies and their constructs were independently rated based oil the direction of significant effects, quality of execution, design suitability, and frequency. Methodology from the Guide to Community Preventive Services was used to systematically review and synthesize findings. Results: Twenty five psychosocial constructs spanning 35 Studies were reviewed (14 prospective and 21 cross-sectional/descriptive studies). Strong evidence was found for self-efficacy, social support, and knowledge as predictors of adult fruit and vegetable intake. Weaker evidence was found for variables including barriers, intentions, attitudes/beliefs, stages of change, and autonomous motivation. Conclusions: The findings underscore the need to design future behavioral interventions that use strong experimental designs with efficacious constructs and to conduct formal mediation analyses to determine the strength of these potential predictors of fruit and vegetable intake. C1 [Shaikh, Abdul R.] NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Yaroch, Amy L.; Nebeling, Linda] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Yeh, Ming-Chin] CUNY Hunter Coll, New York, NY 10021 USA. [Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RP Shaikh, AR (reprint author), NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,EPN 4062,MSC 7335, Bethesda, MD 20892 USA. EM shaikhab@mail.nih.gov NR 85 TC 149 Z9 149 U1 5 U2 47 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 JUN PY 2008 VL 34 IS 6 BP 535 EP 543 DI 10.1016/j.amepre.2007.12.028 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 305HS UT WOS:000256169500013 PM 18471592 ER PT J AU Novak, MFSX Dettmer, AM AF Novak, M. F. S. X. Dettmer, A. M. TI Observational methodologies symposium: Methods from the field, zoo and laboratory SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Dettmer, A. M.] Univ Massachusetts, Amherst, MA 01003 USA. [Novak, M. F. S. X.] NICHD, NIH, LCE, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 3 BP 21 EP 21 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800004 ER PT J AU Soltis, J Wesolek, CM Leighty, KA Savage, A Newman, JD AF Soltis, J. Wesolek, C. M. Leighty, K. A. Savage, A. Newman, J. D. TI The expression of emotion in the voiced sounds of rhesus monkeys and African elephants SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Soltis, J.; Wesolek, C. M.; Leighty, K. A.; Savage, A.] Disneys Anim Kingdom, Bay Lake, FL 32830 USA. [Newman, J. D.] NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 23 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 10 BP 23 EP 24 PG 2 WC Zoology SC Zoology GA 309JP UT WOS:000256456800011 ER PT J AU Ionica, CS Robbins, KL Novak, MFSX Suomi, SJ AF Ionica, C. S. Robbins, K. L. Novak, M. F. S. X. Suomi, S. J. TI Multimodal data input using touchscreen technology, voice recording and speech recognition in adverse field conditions SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Ionica, C. S.; Robbins, K. L.; Novak, M. F. S. X.; Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. RI Ionica, Consuel/A-5186-2009 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 11 BP 24 EP 24 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800012 ER PT J AU Chen, SA Schwandt, ML Lindell, SG Lopez-Coleman, N Peele, LN Woodward, RA Robbins, KL Suomi, SJ Heilig, MA Barr, CS AF Chen, S. A. Schwandt, M. L. Lindell, S. G. Lopez-Coleman, N. Peele, L. N. Woodward, R. A. Robbins, K. L. Suomi, S. J. Heilig, M. A. Barr, C. S. TI Reduction of acute stress-induced behaviors by a corticotropin releasing factor receptor 1 antagonist in rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Chen, S. A.; Schwandt, M. L.; Lindell, S. G.; Lopez-Coleman, N.; Peele, L. N.; Heilig, M. A.; Barr, C. S.] NIAAA, NIH, Lab Clin & Translat Studies, Anim Ctr, Poolesville, MD 20837 USA. [Woodward, R. A.] NICHD, NIH, Res Anim Management Branch, Bethesda, MD USA. [Robbins, K. L.; Suomi, S. J.] NICHD, NIH, Comparat Ethol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 16 BP 25 EP 26 PG 2 WC Zoology SC Zoology GA 309JP UT WOS:000256456800017 ER PT J AU Schwandt, ML Lindell, SG Lindell, C Higley, JD Suomi, SJ Heilig, M Barr, CS AF Schwandt, M. L. Lindell, S. G. Lindell, C. Higley, J. D. Suomi, S. J. Heilig, M. Barr, C. S. TI OPRM1 gene variation influences HPA axis function in rhesus macaque (Macaca mulatta) mothers SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Schwandt, M. L.; Lindell, S. G.; Heilig, M.; Barr, C. S.] NIAAA LCTS, NIH, Anim Ctr, Poolesville, MD 20837 USA. [Lindell, C.; Suomi, S. J.] NICHD, NIH, Bethesda, MD USA. [Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 15 BP 25 EP 25 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800016 ER PT J AU Herman, K Schwandt, M Ruggiero, A Barr, CS Suomi, SJ AF Herman, K. Schwandt, M. Ruggiero, A. Barr, C. S. Suomi, S. J. TI Gene-environment interaction predicts fear-related behavior in infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Herman, K.; Ruggiero, A.; Suomi, S. J.] NIH, Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20842 USA. [Herman, K.] Univ Maryland, Child Dev Lab, College Pk, MD 20742 USA. [Schwandt, M.; Barr, C. S.] NIAAA, Primate Unit, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 32 BP 31 EP 31 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800033 ER PT J AU Barrett, CE Noble, P Hanson, E Pine, DS Winslow, JT Nelson, EE AF Barrett, C. E. Noble, P. Hanson, E. Pine, D. S. Winslow, J. T. Nelson, E. E. TI Early adverse rearing experiences alter sleep-wake patterns and basal cortisol levels in juvenile rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Barrett, C. E.; Noble, P.; Hanson, E.; Pine, D. S.; Winslow, J. T.; Nelson, E. E.] NIMH, NIH, Dickerson, MD 20842 USA. RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 37 BP 32 EP 33 PG 2 WC Zoology SC Zoology GA 309JP UT WOS:000256456800038 ER PT J AU Jani, K Dettmer, AM Suomi, SJ Novak, MFSX Thierry, B Timme, A Meyer, JS Novak, MA AF Jani, K. Dettmer, A. M. Suomi, S. J. Novak, M. F. S. X. Thierry, B. Timme, A. Meyer, J. S. Novak, M. A. TI Hair cortisol concentrations in tonkean (macaca tonkeana) and rhesus (M. Mulatta) macaques, two species with different levels of social tolerance SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Jani, K.; Dettmer, A. M.; Meyer, J. S.; Novak, M. A.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Suomi, S. J.; Novak, M. F. S. X.] NICHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. [Thierry, B.; Timme, A.] CNRS, IPHC, Dept Ecol Physiol & Ethol, F-75700 Paris, France. [Meyer, J. S.; Novak, M. A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 39 BP 33 EP 33 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800040 ER PT J AU Mallott, EK Novak, MFSX Robbins, KL Ionica, CS Miller, ML Kerschner, EA Suomi, SJ AF Mallott, E. K. Novak, M. F. S. X. Robbins, K. L. Ionica, C. S. Miller, M. L. Kerschner, E. A. Suomi, S. J. TI Development of infant-mother independence in macaca mulatta housed in modified nuclear-family housing SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Mallott, E. K.; Novak, M. F. S. X.; Robbins, K. L.; Ionica, C. S.; Miller, M. L.; Kerschner, E. A.; Suomi, S. J.] NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. RI Ionica, Consuel/A-5186-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 38 BP 33 EP 33 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800039 ER PT J AU Flygare, RA Graham, KN Schwandt, ML Lindell, SG Barr, CS Suomi, SJ Higley, J AF Flygare, R. A. Graham, K. N. Schwandt, M. L. Lindell, S. G. Barr, C. S. Suomi, S. J. Higley, J. TI Biological and adoptive mother-infant relationships across the first six months of life: More dyadic conflict, infant withdrawal, and anxiety in adoptive dyads SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Flygare, R. A.; Graham, K. N.; Higley, J.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Schwandt, M. L.; Lindell, S. G.; Barr, C. S.] NIAAA, NIH, Anim Ctr, LCTS, Poolesville, MD 20837 USA. [Suomi, S. J.] NICHD, NIH, Anim Ctr, LCE, Bethesda, 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 43 BP 34 EP 35 PG 2 WC Zoology SC Zoology GA 309JP UT WOS:000256456800044 ER PT J AU Kay, DB Higley, JD Marsiske, M Suomi, SJ AF Kay, D. B. Higley, J. D. Marsiske, M. Suomi, S. J. TI Temperament and daytime sleepiwake states in neonatal rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Kay, D. B.; Marsiske, M.] Univ Florida, Gainesville, FL 32610 USA. [Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, Bethesda, 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 41 BP 34 EP 34 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800042 ER PT J AU Graves, HM Kerschner, EA Davis, EB Novak, MFSX Ruggiero, AM Suomi, SJ AF Graves, H. M. Kerschner, E. A. Davis, E. B. Novak, M. F. S. X. Ruggiero, A. M. Suomi, S. J. TI The effects of length and type of rearing condition on the development of maladaptive behavior in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Graves, H. M.; Kerschner, E. A.; Davis, E. B.; Novak, M. F. S. X.; Ruggiero, A. M.; Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 44 BP 35 EP 35 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800045 ER PT J AU Kurdziel, LB Young, JE Ingram, DK Mattison, JA AF Kurdziel, L. B. Young, J. E. Ingram, D. K. Mattison, J. A. TI Gender differences on set-shifting and fine motor function tasks in adult rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Kurdziel, L. B.; Young, J. E.] SoBran Inc, Fairfax, VA 22031 USA. [Ingram, D. K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. [Mattison, J. A.] NIA, Lab Expt Gerontol, NIH, Bethesda, MD 20892 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 47 BP 36 EP 36 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800048 ER PT J AU Ruggiero, AM Dettmer, AM Novak, MA Meyer, JS Suomi, SJ AF Ruggiero, A. M. Dettmer, A. M. Novak, M. A. Meyer, J. S. Suomi, S. J. TI Basal cortisol levels are unrelated to temperament in rhesus macaque infants (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Ruggiero, A. M.; Dettmer, A. M.; Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. [Dettmer, A. M.; Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 48 BP 36 EP 36 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800049 ER PT J AU Howell, S Schwandt, M Champagne, J Westergaard, G Higley, J AF Howell, S. Schwandt, M. Champagne, J. Westergaard, G. Higley, J. TI Individual differences in biobehavioral profiles may impact drug results SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Howell, S.] Mannheimer Fdn Inc, NIH, Lab Clin & Translat Studies, Sect Study Primate Models Psychopathol, Clewiston, FL 33440 USA. [Schwandt, M.] NIAAA, Dept Psychol, Bethesda, MD USA. [Higley, J.] Brigham Young Univ, Provo, UT 84602 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 50 BP 37 EP 37 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800051 ER PT J AU Dettmer, AM Novak, MA Meyer, JS Suomi, SJ AF Dettmer, A. M. Novak, M. A. Meyer, J. S. Suomi, S. J. TI Hair cortisol concentrations predict infant social behavior in differently-reared rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Dettmer, A. M.; Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Suomi, S. J.] NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 56 BP 39 EP 39 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800057 ER PT J AU Higley, J Barr, CS Garber, PA AF Higley, J. Barr, C. S. Garber, P. A. TI Successful secrets of simian scripts: Publishing before you perish SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Higley, J.] Brigham Young Univ, Dept Psychol, Provo, UT 84057 USA. [Higley, J.; Barr, C. S.] NIAAA, NIH, Primate Sect, Poolesville, MD 20837 USA. [Higley, J.; Garber, P. A.] UIUC, Dept Anthropol, Urbana, IL 61801 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 67 BP 42 EP 42 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800068 ER PT J AU Dettmer, AM Novak, MFSX Suomi, SJ Novak, MA Meyer, JS AF Dettmer, A. M. Novak, M. F. S. X. Suomi, S. J. Novak, M. A. Meyer, J. S. TI Long-term HPA profile predicts object permanence performance in infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Dettmer, A. M.; Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Novak, M. F. S. X.; Suomi, S. J.] NICHD, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. [Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 82 BP 47 EP 48 PG 2 WC Zoology SC Zoology GA 309JP UT WOS:000256456800083 ER PT J AU Berman, CM Ogawa, H Ionica, CS Yin, H Li, J AF Berman, C. M. Ogawa, H. Ionica, C. S. Yin, H. Li, J. TI Variation over time in grooming kin bias among wild female Tibetan macaques (Macaca thibetana huangshanensis) on Huangshan, China, supports the time constraints hypothesis SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Berman, C. M.; Ionica, C. S.] SUNY Buffalo, Dept Anthropol & Program Evolut Ecol & Behav, Buffalo, NY 14261 USA. [Ogawa, H.] Chukyo Univ, Sch Int Liberal Arts, Nagoya, Aichi, Japan. [Ionica, C. S.] NICHHD, Comparat Ethol Lab, Bethesda, MD USA. [Yin, H.; Li, J.] Anhui Univ, Sch Life Sci, Hefei, Peoples R China. RI Ionica, Consuel/A-5186-2009 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 87 BP 49 EP 49 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800088 ER PT J AU Paukner, A Huntsberry, ME Ferrari, PF Suomi, SJ AF Paukner, A. Huntsberry, M. E. Ferrari, P. F. Suomi, S. J. TI Imitation recognition in capuchin monkeys SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Paukner, A.; Huntsberry, M. E.; Ferrari, P. F.; Suomi, S. J.] NIH, Comparat Ethol Lab, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 103 BP 54 EP 54 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800104 ER PT J AU Ferrari, P Paukner, A Ruggiero, A Darcey, L Unbehagen, S Suomi, SJ AF Ferrari, P. Paukner, A. Ruggiero, A. Darcey, L. Unbehagen, S. Suomi, S. J. TI Interindividual differences in neonatal imitation and the development of action chains in rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Primatologists CY JUN 18-21, 2008 CL Palm Beach Zoo, West Palm Beach, FL SP Amer Soc Primatol HO Palm Beach Zoo C1 [Ferrari, P.] Univ Parma, Dipartimento Biol Evolut & Funzionale, I-43100 Parma, Italy. [Ferrari, P.; Paukner, A.; Ruggiero, A.; Darcey, L.; Unbehagen, S.; Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2008 VL 70 SU 1 MA 133 BP 64 EP 64 PG 1 WC Zoology SC Zoology GA 309JP UT WOS:000256456800133 ER PT J AU Insel, TR AF Insel, Thomas R. TI Assessing the economic costs of serious mental illness SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd,Rm 8235,MSC 9669, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 9 TC 89 Z9 93 U1 0 U2 16 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 JUN PY 2008 VL 165 IS 6 BP 663 EP 665 DI 10.1176/appi.ajp.2008.08030366 PG 3 WC Psychiatry SC Psychiatry GA 307YE UT WOS:000256354700001 PM 18519528 ER PT J AU Vitiello, B AF Vitiello, Benedetto TI Improving decision making in the treatment of ADHD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MEDICATION C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Rm 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 8 TC 4 Z9 4 U1 3 U2 5 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 JUN PY 2008 VL 165 IS 6 BP 666 EP 667 DI 10.1176/appi.ajp.2008.08030365 PG 2 WC Psychiatry SC Psychiatry GA 307YE UT WOS:000256354700002 PM 18519529 ER PT J AU Kessler, RC Heeringa, S Lakoma, MD Petukhova, M Rupp, AE Schoenbaum, M Wang, PS Zaslavsky, AM AF Kessler, Ronald C. Heeringa, Steven Lakoma, Matthew D. Petukhova, Maria Rupp, Agnes E. Schoenbaum, Michael Wang, Philip S. Zaslavsky, Alan M. TI Individual and societal effects of mental disorders on earnings in the united states: Results from the national comorbidity survey replication SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DSM-IV DISORDERS; PSYCHIATRIC-DISORDERS; SOCIAL-CONSEQUENCES; NCS-R; IMPACT; PREVALENCE; RETRANSFORMATION; PROBABILITY; LIFETIME; OUTCOMES AB Objective: The purpose of this report was to update previous estimates of the association between mental disorders and earnings. Current estimates for 2002 are based on data from the National Comorbidity Survey Replication (NCS-R). Method: The NCS-R is a nationally representative survey of the U. S. household population that was administered from 2001 to 2003. Following the same basic approach as prior studies, with some modifications to improve model fitting, the authors predicted personal earnings in the 12 months before interview from information about 12-month and lifetime DSM-IV mental disorders among respondents ages 18-64, controlling for socio-demographic variables and substance use disorders. The authors used conventional demographic rate standardization methods to distinguish predictive effects of mental disorders on amount earned by persons with earnings from predictive effects on probability of having any earnings. Results: A DSM-IV serious mental illness in the preceding 12 months significantly predicted reduced earnings. Other 12-month and lifetime DSM-IV/CIDI mental disorders did not. Respondents with serious mental illness had 12-month earnings averaging $16,306 less than other respondents with the same values for control variables ($26,435 among men, $9,302 among women), for a societal-level total of $193.2 billion. Of this total, 75.4% was due to reduced earnings among mentally ill persons with any earnings (79.6% men, 69.6% women). The remaining 24.6% was due to reduced probability of having any earnings. Conclusions: These results add to a growing body of evidence that mental disorders are associated with substantial societal-level impairments that should be taken into consideration when making decisions about the allocation of treatment and research resources. C1 [Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu FU NIMH NIH HHS [U01 MH-60220, U01 MH060220, U01 MH060220-07]; PHS HHS [HHSN271200700030C] NR 40 TC 150 Z9 151 U1 3 U2 17 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 JUN PY 2008 VL 165 IS 6 BP 703 EP 711 DI 10.1176/appi.ajp.2008.08010126 PG 9 WC Psychiatry SC Psychiatry GA 307YE UT WOS:000256354700011 PM 18463104 ER PT J AU Marsh, AA Finger, EC Mitchell, DGV Reid, ME Sims, C Kosson, DS Towbin, KE Leibenluft, E Pine, DS Blair, RJR AF Marsh, Abigail A. Finger, Elizabeth C. Mitchell, Derek G. V. Reid, Marguerite E. Sims, Courtney Kosson, David S. Towbin, Kenneth E. Leibenluft, Ellen Pine, Daniel S. Blair, R. J. R. TI Reduced amygdala response to fearful expressions in children and adolescents with callous-unemotional traits and disruptive behavior disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 08-12, 2006 CL San Francisco, CA SP Cognit Neurosci Soc ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FACIAL EXPRESSIONS; NEURAL RESPONSES; PSYCHOPATHIC TENDENCIES; CONDUCT PROBLEMS; ORBITOFRONTAL CORTEX; ANTISOCIAL-BEHAVIOR; HUMAN BRAIN; EMOTION AB Objective: Extensive work implicates abnormal amygdala activation in emotional facial expression processing in adults with callous-unemotional traits. However, no research has examined amygdala response to emotional facial expressions in adolescents with disruptive behavior and callous-unemotional traits. Moreover, despite high comorbidity of callous-unemotional traits and attention deficit hyperactivity disorder (ADHD), no research has attempted to distinguish neural correlates of pediatric callous-unemotional traits and ADHD. Method: Participants were 36 children and adolescents (ages 10-17 years); 12 had callous-unemotional traits and either conduct disorder or oppositional defiant disorder, 12 had ADHD, and 12 were healthy comparison subjects. Functional MRI was used to assess amygdala activation patterns during processing of fearful facial expressions. Patterns in the callous-unemotional traits group were compared with those in the ADHD and comparison groups. Results: In youths with callous-unemotional traits, amygdala activation was reduced relative to healthy comparison subjects and youths with ADHD while processing fearful expressions, but not neutral or angry expressions. Functional connectivity analyses demonstrated greater correlations between the amygdala and the ventromedial prefrontal cortex in comparison subjects and youths with ADHD relative to those with callous-unemotional traits. Symptom severity in the callous-unemotional traits groups was negatively correlated with connectivity between amygdala and ventromedial prefrontal cortex. Conclusions: This is the first study to demonstrate reduced amygdala responsiveness in youths with callous-unemotional traits. These findings support the contention that callous and unemotional personality traits are associated with reduced amygdala response to distress-based social cues. C1 [Marsh, Abigail A.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Psychiat, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada. Rosalind Franklin Univ Med Sci, Dept Psychol, N Chicago, IL USA. RP Marsh, AA (reprint author), NIMH, Mood & Anxiety Program, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM amarsh@post.harvard.edu RI Finger, Elizabeth/B-6453-2015 FU Intramural NIH HHS NR 49 TC 333 Z9 340 U1 10 U2 74 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 JUN PY 2008 VL 165 IS 6 BP 712 EP 720 DI 10.1176/appi.ajp.2007.07071145 PG 9 WC Psychiatry SC Psychiatry GA 307YE UT WOS:000256354700012 PM 18281412 ER PT J AU Rietschel, M Beckmann, L Strohmaier, J Georgi, A Karpushova, A Schirmbeck, F Boesshenz, KV Schmal, C Burger, C Abou Jamra, R Schumacher, J Hofels, S Kumsta, R Entringer, S Krug, A Markov, V Maier, W Propping, P Wust, S Kircher, T Nothen, MM Cichon, S Schulze, TG AF Rietschel, Marcella Beckmann, Lars Strohmaier, Jana Georgi, Alexander Karpushova, Anna Schirmbeck, Frederike Boesshenz, Katja V. Schmael, Christine Buerger, Christin Abou Jamra, Rami Schumacher, Johannes Hoefels, Susanne Kumsta, Robert Entringer, Sonja Krug, Axel Markov, Valentin Maier, Wolfgang Propping, Peter Wuest, Stefan Kircher, Tilo Noethen, Markus M. Cichon, Sven Schulze, Thomas G. TI G72 and its association with major depression and neuroticism in large population-based groups from Germany SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat ID GENOME-WIDE ASSOCIATION; AMINO-ACID OXIDASE; BIPOLAR-AFFECTIVE-DISORDER; HAPLOTYPE SHARING ANALYSIS; G72/G30 GENE LOCUS; PERSECUTORY DELUSIONS; DAOA/G30 LOCUS; PSYCHIATRIC-DISORDERS; DIAGNOSTIC BOUNDARIES; SUSCEPTIBILITY GENE AB Objective: G72 is among the most frequently replicated vulnerability genes for schizophrenia and bipolar disorder. The authors previously found identical haplotypes of markers M23 and M24 to be associated with schizophrenia, bipolar disorder, and panic disorder. Given both the well-recognized familial clustering across these disorders and recent linkage findings implicating the region harboring G72 in the etiology of major depression and panic disorder, we can hypothesize that G72 should also be involved in the etiology of major depression. Neuroticism, measuring trait anxiety, may be the endophenotypic link underlying genetic associationswith G72 across diagnostic boundaries. The authors tested whether the previously observed risk haplotypes are also associated with major depression and neuroticism. Method: The authors performed a standard haplotype analysis in a group of 500 major depression patients and 1,030 population-based comparison subjects. The authors also performed an exploratory analysis on 10 additional G72 markers using a novel haplotype-sharing approach. They performed a quantitative trait haplotype analysis in an independent group of 907 individuals phenotyped for neuroticism. Results: The previously identified M23-M24 risk haplotype was significantly associated with major depression and high levels of neuroticism. The haplotype-sharing analysis also implicated the same region, whereas more proximal markers showed no association with major depression. Conclusions: This is the first study to the authors' knowledge to implicate the G72 locus in the etiology of major depression and neuroticism. The results strengthen the notion of a genetic overlap between diagnoses, commonly conceptualized as distinct entities. Neuroticism may constitute the common underlying endophenotypic link. C1 Univ Heidelberg, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. German Canc Res Ctr, Unit Genet Epidemiol German, D-6900 Heidelberg, Germany. Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. Univ Bonn, Dept Genom, Life Brain Ctr, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany. Univ Trier, Dept Psychobiol, Trier, Germany. Univ Aachen, Rhein Westfal TH Aachen, D-5100 Aachen, Germany. Univ Aachen, Dept Psychiat & Psychotherapy, D-5100 Aachen, Germany. RP Schulze, TG (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, 35 Convent Dr,Rm 1A202, Bethesda, MD 20892 USA. EM schulzet@mail.nih.gov RI Schulze, Thomas/H-2157-2013; Kumsta, Robert/P-9641-2016; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schirmbeck, Frederike/G-8187-2016; Schumacher, Johannes/F-4970-2015 OI Kumsta, Robert/0000-0001-6006-6958; Georgi, Alexander/0000-0002-1499-8524; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Nothen, Markus/0000-0002-8770-2464; Schumacher, Johannes/0000-0001-9217-6457 NR 78 TC 36 Z9 38 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2008 VL 165 IS 6 BP 753 EP 762 DI 10.1176/appi.ajp.2008.07060883 PG 10 WC Psychiatry SC Psychiatry GA 307YE UT WOS:000256354700017 PM 18346999 ER PT J AU Ramos, RG Olden, K AF Ramos, Rosemarie G. Olden, Kenneth TI The prevalence of metabolic syndrome among US women of childbearing age SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; POLYCYSTIC-OVARY-SYNDROME; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; SCIENTIFIC STATEMENT; OBESITY; POPULATION AB Objectives. We sought to determine whether the prevalence of metabolic syndrome among US women of childbearing age (18-44 years) has increased since 1988 and to estimate its current prevalence by race/ethnicity and risk that a maternal history of select metabolic syndrome characteristics imposes on offspring. Methods. We used survey-specific data analysis methods to examine data from the National Health and Nutrition Examination Surveys conducted from 1988 to 2004. Results. The prevalence of the metabolic syndrome phenotype and 2 of its clinical correlates significantly increased between 1988 and 2004 (increase for metabolic syndrome phenotype=7.6%, for obesity=13.3%, and for elevated C-reactive protein=10.6%; P <.001 for all 3). Hispanic women were more likely than were White women to possess the phenotype (P=.004). Women who reported that their mothers had been diagnosed with diabetes were more likely to possess the phenotype than those whose mothers had not been so diagnosed (odds ratio=1.9; 95% confidence interval =1.3, 2.8). Conclusions. The current trends of metabolic syndrome among women of childbearing age demonstrate the need for additional rigorous investigations regarding its long-term effects in these women and their offspring. C1 [Ramos, Rosemarie G.; Olden, Kenneth] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM ramosr@niehs.nih.gov NR 45 TC 39 Z9 40 U1 0 U2 0 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 JUN PY 2008 VL 98 IS 6 BP 1122 EP 1127 DI 10.2105/AJPH.2007.120055 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 308BK UT WOS:000256363100030 PM 18445796 ER PT J AU Chamberlain, CE Penzak, SR Alfaro, RM Wesley, R Daniels, CE Hale, D Kirk, AD Mannon, RB AF Chamberlain, C. E. Penzak, S. R. Alfaro, R. M. Wesley, R. Daniels, C. E. Hale, D. Kirk, A. D. Mannon, R. B. TI Pharmacokinetics of low and maintenance dose valganciclovir in kidney transplant recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE kidney transplantation; pharmacokinetics; prophylaxis; valganciclovir ID ORAL GANCICLOVIR; CYTOMEGALOVIRUS DISEASE; PROPHYLAXIS; PREVENTION; EFFICACY; SAFETY; INFECTION; RETINITIS; THERAPY; TRIAL AB Valganciclovir is commonly used for cytomegalovirus (CMV) prophylaxis in renal transplant patients. A fixed dose of 900 mg daily is typically recommended, however, there has never been a formal pharmacokinetic study comparing various doses in renal transplant patients. We therefore compared the pharmacokinetic characteristics of intravenous ganciclovir (IV GCV) and oral ganciclovir (GCV) with two different doses of valganciclovir (VGCV) in an open-label crossover study. Ten adult kidney recipients participated in a four-phase crossover treatment schedule of IV GCV (2.5 mg/kg every 12 h), VGCV (900 mg daily), VGCV (450 mg daily) and oral GCV (1000 mg Q8 H). IV GCV and oral VGCV 900 mg daily achieved similar values for AUC(0-24) (median 60.63 vs. 62.86 mu g/h/mL). Oral VGCV 450 mg achieved comparable AUC(0-24) values as oral GCV 1000 mg Q8 H (median AUC(0-24) 35.9 vs. 29.04 mu g/h/mL). Oral VGCV 900 mg daily provided systemic GCV exposure similar to IV GCV and confirms PV 16 000 study results. Further, VGCV 450 mg daily provided comparable systemic exposure versus oral GCV. Due to its favorable pharmacokinetic profile, data herein suggest that VGCV can be used in the early post-kidney transplant period, and that 450 mg daily provides ample drug exposure for effective CMV prophylaxis in kidney transplant patients. C1 [Chamberlain, C. E.; Penzak, S. R.; Alfaro, R. M.] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Wesley, R.] NIH, CC, Bethesda, MD 20892 USA. [Kirk, A. D.; Mannon, R. B.] NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. [Daniels, C. E.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Hale, D.] Univ Florida, Div Transplantat, Jacksonville, FL USA. RP Chamberlain, CE (reprint author), NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. EM cchamberla@cc.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS [Z01 CL005095-06, Z99 CL999999] NR 24 TC 20 Z9 20 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2008 VL 8 IS 6 BP 1297 EP 1302 DI 10.1111/j.1600-6143.2008.02220.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 307VP UT WOS:000256347100024 PM 18444933 ER PT J AU Miller, LH Duffy, PE AF Miller, Louis H. Duffy, Patrick E. TI Robert S. Desowitz - January 2, 1926-March 24, 2008 - Obituary SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Biographical-Item C1 [Miller, Louis H.] NIAID, NIH, Bethesda, MD 20892 USA. [Duffy, Patrick E.] SBRI, Seattle, WA USA. [Duffy, Patrick E.] UW, Seattle, WA USA. RP Miller, LH (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 2008 VL 78 IS 6 BP 849 EP 850 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 310BS UT WOS:000256504500001 ER PT J AU Capone, G De Marinis, A Simone, S Kusalik, A Kanduc, D AF Capone, G. De Marinis, A. Simone, S. Kusalik, A. Kanduc, D. TI Mapping the human proteome for non-redundant peptide islands SO AMINO ACIDS LA English DT Article DE human proteome; redundant peptide sequences; quantitative proteomic redundancy; qualitative proteomic redundancy ID FACTOR-VIII ANTIBODIES; E3 UBIQUITIN LIGASES; BREAST-CANCER CELLS; MULTIPLE-SCLEROSIS; PROSTATE-CANCER; AUTOIMMUNE ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; HUMAN-PAPILLOMAVIRUS; ACQUIRED HEMOPHILIA; GASTRIC-CARCINOMA AB We describe immune-proteome structures using libraries of protein fragments that define a structural immunological alphabet. We propose and validate such an alphabet as i) composed of letters of five consecutive amino acids, pentapeptide units being sufficient minimal antigenic determinants in a protein, and ii) characterized by low-similarity to human proteins, so representing structures unknown to the host and potentially able to evoke an immune response. In this context, we have thoroughly sifted through the entire human proteome searching for non-redundant protein motifs. Here, for the first time, a complete sequence redundancy dissection of the human proteome has been conducted. The non-redundant peptide islands in the human proteome have been quantified and catalogued according to the amino acid length. The library of uniquely occurring n-peptide sequences that was obtained is characterized by a logarithmic decrease of the number of non-redundant peptides as a function of the peptide length. This library represents a highly specific catalogue of molecular protein signatures, the possible use of which in cancer/autoimmunity research is discussed, with a major focus on non-redundant dodecamer sequences. C1 [Kanduc, D.] NIH, Ctr Clin, Immunogenet Lab, Dept Transfus Med, Bethesda, MD 20892 USA. [Capone, G.; De Marinis, A.; Simone, S.; Kanduc, D.] Univ Bari, Dept Biochem & Mol Biol Ernesto Quagliariello, Bari, Italy. [Kusalik, A.] Univ Saskatchewan, Dept Comp Sci, Saskatoon, SK S7N 0W0, Canada. RP Kanduc, D (reprint author), NIH, Ctr Clin, Immunogenet Lab, Dept Transfus Med, 10 Ctr Dr,Bldg 10,Room 1N224, Bethesda, MD 20892 USA. EM kanducd@cc.nih.gov NR 82 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD JUN PY 2008 VL 35 IS 1 BP 209 EP 216 DI 10.1007/s00726-007-0563-7 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309QQ UT WOS:000256475700026 PM 17701099 ER PT J AU Le Couteur, DG Warren, A Cogger, VC Smedsrod, B Sorensen, KK De Cabo, R Fraser, R Mccuskey, RS AF Le Couteur, David G. Warren, Alessandra Cogger, Victoria C. Smedsrod, Bard Sorensen, Karen K. De Cabo, Rafael Fraser, Robin Mccuskey, Robert S. TI Old age and the hepatic sinusoid SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE liver; aging; liver sinusoidal endothelial cell; chylomicron remnant; endocytosis; microcirculation; stellate cell; Kupffer cell; caloric restriction ID LIVER ENDOTHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; GLYCATION END-PRODUCTS; PERFUSED-RAT-LIVER; KUPFFER CELLS; DRUG CLEARANCE; BLOOD-FLOW; T-CELLS; IN-VIVO; CHOLESTEROL-METABOLISM AB Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial upregulation of von Willebrand factor and ICAM-1 with reduced expression of caveolin-1. These changes have been termed age-related pseudocapillarization. The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age-related changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age-related diseases. C1 [Le Couteur, David G.; Warren, Alessandra; Cogger, Victoria C.] Univ Sydney, Ctr Educ & Res Aging, Sydney, NSW 2139, Australia. [Le Couteur, David G.; Warren, Alessandra; Cogger, Victoria C.] Concord RG Hosp, Sydney, NSW 2139, Australia. [Smedsrod, Bard; Sorensen, Karen K.; Mccuskey, Robert S.] Univ Tromso, Inst Med Biol, Dept Cell Biol & Histol, Tromso, Norway. [De Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Fraser, Robin] Univ Otago, Christchurch Sch Med, Christchurch, New Zealand. [Mccuskey, Robert S.] Univ Arizona, Coll Med, Dept Cell Biol & Anat, Tucson, AZ USA. RP Le Couteur, DG (reprint author), Univ Sydney, Ctr Educ & Res Aging, Sydney, NSW 2139, Australia. EM dlecouteur@med.usyd.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU NIA NIH HHS [R21 AG-02582] NR 93 TC 65 Z9 66 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8486 J9 ANAT REC JI Anat. Rec. PD JUN PY 2008 VL 291 IS 6 BP 672 EP 683 DI 10.1002/ar.20661 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA 313CN UT WOS:000256718800008 PM 18484614 ER PT J AU Hernandez-Trujillo, VP Fleisher, TA AF Hernandez-Trujillo, Vivian P. Fleisher, Thomas A. TI Interpretation of flow cytometry in primary immunodeficiency disorders SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; DIGEORGE-SYNDROME; CLINICAL FINDINGS; MUTATIONS; DIAGNOSIS; LYMPHOCYTES; DEFICIENCY; ARTEMIS C1 [Hernandez-Trujillo, Vivian P.] Miami Childrens Hosp, Div Clin Immunol & Allergy, Miami, FL USA. [Fleisher, Thomas A.] NIH, Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Hernandez-Trujillo, VP (reprint author), Miami Childrens Hosp, Div Clin Immunol, 3100 SW 62 Ave, Miami, FL 33155 USA. EM vivian.hernandez-trujillo@mch.com NR 25 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUN PY 2008 VL 100 IS 6 BP 612 EP 615 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 309WS UT WOS:000256491500018 PM 18592828 ER PT J AU King, AC Ahn, DF Atienza, AA Kraemer, HC AF King, Abby C. Ahn, David F. Atienza, Audie A. Kraemer, Helena C. TI Exploring refinements in targeted behavioral medicine intervention to advance public health SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE targeted intervention; moderator analysis; RCT; exploratory analysis ID SIGNAL-DETECTION METHODOLOGY; PHYSICAL-ACTIVITY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; LOW-GLYCEMIC LOAD; SMOKING-CESSATION; LOGISTIC-REGRESSION; CLINICAL-TRIALS; NICOTINE DEPENDENCE; STATISTICAL-METHODS AB Background Similar to other fields, a targeted behavioral medicine perspective can aid decision-making related to participant-intervention matching. Purpose To present one potentially useful definition of intervention targeting activity; describe potential targeting domains of particular relevance to behavioral medicine; discuss different statistical approaches to aid the targeted intervention development process; and discuss the challenges and opportunities accompanying the incorporation of targeted intervention development methods into behavioral randomized clinical trial (RCT) research. Methods Drawing from recent conceptual work by the MacArthur group and other scientists in the field, methods and approaches to undertaking moderator analysis are discussed. Results Examples of moderator analyses are provided which reflect the different statistical methods and variable domains that may serve as moderators of intervention success. Conclusions The recommended exploratory work can help to make the most efficient use of RCTs to identify the best paths for subsequent RCT development in a resource-constrained era. C1 [King, Abby C.; Ahn, David F.] Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [King, Abby C.; Ahn, David F.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Atienza, Audie A.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Promot Res Branch,NIH, Bethesda, MD 20892 USA. [Kraemer, Helena C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP King, AC (reprint author), Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. EM king@stanford.edu FU NIA NIH HHS [R01AG021010] NR 79 TC 27 Z9 27 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2008 VL 35 IS 3 BP 251 EP 260 DI 10.1007/s12160-008-9032-0 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 339CA UT WOS:000258554500001 PM 18568380 ER PT J AU Nelson, W Reyna, VF Fagerlin, A Lipkus, I Peters, E AF Nelson, Wendy Reyna, Valerie F. Fagerlin, Angela Lipkus, Isaac Peters, Ellen TI Clinical implications of numeracy: Theory and practice SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Review DE numeracy; quantitative literacy; numerical competence ID FUNCTIONAL HEALTH LITERACY; FUZZY-TRACE THEORY; RISK COMMUNICATION; DECISION-MAKING; QUANTITATIVE INFORMATION; PATIENTS PREFERENCES; QUALITY INFORMATION; GRAPHICAL DISPLAYS; BREAST-CANCER; PROBABILITY AB Background Low numeracy is pervasive and constrains informed patient choice, reduces medication compliance, limits access to treatments, impairs risk communication, and affects medical outcomes; therefore, it is incumbent upon providers to minimize its adverse effects. Purpose We provide an overview of research on health numeracy and discuss its implications in clinical contexts. Conclusions Low numeracy cannot be reliably inferred on the basis of patients' education, intelligence, or other observable characteristics. Objective and subjective assessments of numeracy are available in short forms and could be used to tailor health communication. Low scorers on these assessments are subject to cognitive biases, irrelevant cues (e.g., mood), and sharper temporal discounting. Because prevention of the leading causes of death (e.g., cancer and cardiovascular disease) depends on taking action now to prevent serious consequences later, those low in numeracy are likely to require more explanation of risk to engage in prevention behaviors. Visual displays can be used to make numerical relations more transparent, and different types of displays have different effects (e.g., greater risk avoidance). Ironically, superior quantitative processing seems to be achieved by focusing on qualitative gist and affective meaning, which has important implications for empowering patients to take advantage of the evidence in evidence-based medicine. C1 [Nelson, Wendy] NCI, Basic & Biobehav Res Branch, DCCPS, Bethesda, MD 20892 USA. [Reyna, Valerie F.] Cornell Univ, Ithaca, NY USA. [Fagerlin, Angela] Univ Michigan, Div Gen Internal Med, Ann Arbor VA HSR & D Ctr Excellence, Ann Arbor, MI 48109 USA. [Fagerlin, Angela] Univ Michigan, Ctr Behav & Decis Sci Med, Ann Arbor, MI 48109 USA. [Lipkus, Isaac] Duke Univ, Durham, NC USA. [Peters, Ellen] Decis Res, Eugene, OR USA. [Peters, Ellen] Univ Oregon, Eugene, OR 97403 USA. RP Nelson, W (reprint author), NCI, Basic & Biobehav Res Branch, DCCPS, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM nelsonw@mail.nih.gov FU NCI NIH HHS [R13CA126359, R13 CA126359]; NIMH NIH HHS [MH-061211, R01 MH061211] NR 128 TC 127 Z9 132 U1 9 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2008 VL 35 IS 3 BP 261 EP 274 DI 10.1007/s12160-008-9037-8 PG 14 WC Psychology, Multidisciplinary SC Psychology GA 339CA UT WOS:000258554500002 PM 18677452 ER PT J AU Graham, AL Papandonatos, GD Depue, JD Pinto, BM Borrelli, B Neighbors, CJ Niaura, R Buka, SL Abrams, DB AF Graham, A. L. Papandonatos, G. D. DePue, J. D. Pinto, B. M. Borrelli, B. Neighbors, C. J. Niaura, R. Buka, S. L. Abrams, D. B. TI Lifetime characteristics of participants and non-participants in a smoking cessation trial: Implications for external validity and public health impact SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE recruitment; smoking cessation; generalizability; impact ID FAGERSTROM TOLERANCE QUESTIONNAIRE; POPULATION-BASED RECRUITMENT; DIAGNOSTIC INTERVIEW CIDI; RE-AIM FRAMEWORK; NICOTINE DEPENDENCE; TOBACCO DEPENDENCE; QUIT-SMOKING; PERSONALITY-TRAITS; RANDOMIZED-TRIAL; SELF-HELP AB Background Detailed information about the characteristics of smokers who do and do not participate in smoking cessation treatment is needed to improve efforts to reach, motivate, and treat smokers. Purpose The aim of this study is to explore a broad range of characteristics related to participation in a smoking cessation trial. Methods Eligible smokers were recruited from a longitudinal birth cohort. Participants and non-participants were compared on a broad range of sociodemographics, smoking, psychiatric and substance abuse disorders, personality, and prospective measures from early childhood. Eligible smokers were compared to a matched regional subsample of the Behavioral Risk Factor Surveillance System (BRFSS). Results Few differences were observed, most of which were statistically significant but not clinically meaningful. Compared to non-participants, participants were more likely to be single, have lower income, be more nicotine-dependent, be more motivated to quit, and have higher levels of depressed mood and stress even after covariance of gender, income, and marital status. Sociodemographic differences between participants and the BRFSS sample reflect the skew toward lower socioeconomic status in the original birth cohort. Conclusions The encouraging conclusion is that smokers who enroll in cessation trials may not differ much from non-participants. Information about treatment participants can inform the development of recruitment strategies, improve the tailoring of treatment to individual smoker profiles, help to estimate potential selection bias, and improve estimates of population impact. C1 [Graham, A. L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20007 USA. [Papandonatos, G. D.] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [DePue, J. D.; Pinto, B. M.; Borrelli, B.] Miriam Hosp, Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI 02903 USA. [Neighbors, C. J.] Columbia Univ, Natl Ctr Addict & Subst Abuse, New York, NY 10017 USA. [Niaura, R.] Butler Hosp Transdisciplinary Res, Providence, RI 02906 USA. [Buka, S. L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Abrams, D. B.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Graham, AL (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Control Program, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM alg45@georgetown.edu; gdp@stat.brown.edu; jdepue@lifespan.org; bpinto@lifespan.org; Belinda_Borrelli@Brown.edu; cneighbors@casacolumbia.org; raymond_niaura@brown.edu; Stephen_Buka@brown.edu; abramsd@od.nih.gov RI Buka, Stephen/H-7335-2014; Papandonatos, George/J-2328-2014; OI Buka, Stephen/0000-0002-8578-9308; Borrelli, Belinda/0000-0002-0859-796X; Papandonatos, George/0000-0001-6770-932X; Graham, Amanda/0000-0003-3036-9653 FU NCI NIH HHS [P50 CA084719] NR 65 TC 23 Z9 23 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2008 VL 35 IS 3 BP 295 EP 307 DI 10.1007/s12160-008-9031-1 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 339CA UT WOS:000258554500005 PM 18414962 ER PT J AU Latimer, AE Williams-Piehota, P Katulak, NA Cox, A Mowad, L Higgins, ET Salovey, P AF Latimer, Amy E. Williams-Piehota, Pamela Katulak, Nicole A. Cox, Ashley Mowad, Linda Higgins, E. Tory Salovey, Peter TI Promoting fruit and vegetable intake through messages tailored to individual differences in regulatory focus SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE psychological tailoring; regulatory focus; health communication; persuasion; Cancer Information Service ID QUESTIONNAIRE; INTERVENTIONS; PREVENTION; CALLERS AB Background Researchers must identify strategies to optimize the persuasiveness of messages used in public education campaigns encouraging fruit and vegetable (FV) intake. Purpose This study examined whether tailoring messages to individuals' regulatory focus (RF), the tendency to be motivated by promotion versus prevention goals, increased the persuasiveness of messages encouraging greater FV intake. Method Participants (n=518) completed an assessment of their RF and were randomly assigned to receive either prevention- or promotion-oriented messages. Messages were mailed 1 week, 2 months, and 3 months after the baseline interview. Follow-up assessments were conducted 1 and 4 months after the baseline assessment. Results Regression analyses revealed that at Month 4, the messages were somewhat more efficacious when congruent with participants' RF. Conclusion RF may be a promising target for developing tailored messages promoting increased FV intake, and particularly for encouraging individuals to meet FV guidelines. C1 [Latimer, Amy E.; Williams-Piehota, Pamela; Katulak, Nicole A.; Cox, Ashley; Salovey, Peter] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Latimer, Amy E.] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON K7L 3N6, Canada. [Williams-Piehota, Pamela] RTI Int, Res Triangle Pk, NC 27709 USA. [Mowad, Linda] Yale Canc Ctr, Natl Canc Inst, Canc Informat Serv, New Haven, CT 06510 USA. [Higgins, E. Tory] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Salovey, P (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA. EM amy.latimer@queensu.ca; peter.salovey@yale.edu FU NCI NIH HHS [R01-CA68427, R01 CA068427, N02-CO-01002-75, R01 CA068427-09A2] NR 21 TC 23 Z9 23 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2008 VL 35 IS 3 BP 363 EP 369 DI 10.1007/s12160-008-9039-6 PG 7 WC Psychology, Multidisciplinary SC Psychology GA 339CA UT WOS:000258554500012 PM 18670833 ER PT J AU De Roos, AJ Cooper, GS Alavanja, MC Sandler, DP AF De Roos, Anneclaire J. Cooper, Glinda S. Alavanja, Michael C. Sandler, Dale P. TI Personal and family medical history correlates of rheumatoid arthritis SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE rheumatoid arthritis; autoimmune diseases; autoimmunity; epidemiology; medical history; comorbidities; family history ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MUSCULOSKELETAL DISORDERS; AGRICULTURAL HEALTH; HYGIENE HYPOTHESIS; UNITED-STATES; RISK-FACTORS; SKIN-CANCER; DISEASES; POPULATION; VALIDITY AB PURPOSE: Patients with rheumatoid arthritis (RA) often have comorbidities related to immune dysfunction, however, the timing of comorbidities relative to RA diagnosis and treatment is not clear. We studied personal and family medical history correlates of incident and prevalent RA in women. METHODS: We used a nested case-control design including women in the Agricultural Health Study (AHS). Physician-confirmed cases of RA (n = 135) were matched to five controls each (n = 675) by birth date. We used logistic regression to examine associations between conditions listed in personal and family medical histories and both incident and prevalent RA, as estimated by odds ratios (ORs) and 95% confidence intervals (CIS). RESULTS: The risk of incident RA was associated with personal medical history of nonmelanoma skin cancer (OR = 4.4,95% CI: 1.4-14. 1), asthma or reactive lung disease (OR = 3.7, 95% CI: 1.3-10.5), and cataract (OR = 3.3, 95% CI: 1.0-10.8). Personal history of herpes zoster was associated with prevalent RA (OR = 2.4, 95% CI: 1.2-4.8), but not with incident RA. There were no consistent associations between family medical history and RA. CONCLUSIONS: Patients with medical conditions indicating compromised immunity are at increased risk of developing RA. These results may indicate common pathogenesis of an environmental or genetic nature between such diseases. C1 [De Roos, Anneclaire J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [De Roos, Anneclaire J.] Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. [Cooper, Glinda S.] US EPA, Natl Ctr Hlth Assessment, Washington, DC 20460 USA. [Alavanja, Michael C.] NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sandler, Dale P.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Epidemiol Branch, Res Triangle Pk, NC USA. RP De Roos, AJ (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4 B874, Seattle, WA 98109 USA. EM deroos@u.washington.edu OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z01 ES049030-11] NR 33 TC 2 Z9 2 U1 2 U2 2 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 JUN PY 2008 VL 18 IS 6 BP 433 EP 439 DI 10.1016/j.annepidem.2007.12.011 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 315IZ UT WOS:000256873400001 PM 18346911 ER PT J AU Ross, OA Braithwaite, AT Skipper, LM Kachergus, J Hulihan, MM Middleton, FA Nishioka, K Fuchs, J Gasser, T Maraganore, DM Adler, CH Larvor, L Chartier-Harlin, MC Nilsson, C Langston, JW Gwinn, K Hattori, N Farrer, MJ AF Ross, Owen A. Braithwaite, Adam T. Skipper, Lisa M. Kachergus, Jennifer Hulihan, Mary M. Middleton, Frank A. Nishioka, Kenya Fuchs, Julia Gasser, Thomas Maraganore, Demetrius M. Adler, Charles H. . Larvor, Lydie Chartier-Harlin, Marie-Christine Nilsson, Christer Langston, J. William Gwinn, Katrina Hattori, Nobutaka Farrer, Matthew J. TI Genomic investigation of alpha-synuclein multiplication and parkinsonism SO ANNALS OF NEUROLOGY LA English DT Article ID GENE DUPLICATION; AUTOSOMAL-DOMINANT; LOCUS DUPLICATION; COPY-NUMBER; DISEASE; SNCA; HETEROZYGOSITY; DEMENTIA; CANCER; TRIPLICATION AB Objective: Copy number variation is a common polymorphic phenomenon within the human genome. Although the majority of these events are non-deleterious they can also be highly pathogenic. Herein we characterize five families with parkinsonism that have been identified to harbor multiplication of the chromosomal 4q21 locus containing the a-synuclein gene (SNCA). Methods: A methodological approach using fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) 250K SNP microarrays was used to characterize the multiplication in each family and to identify the genes encoded within the region. The telomeric and centromeric breakpoints of each family were further narrowed using semiquantitative polymerase chain reaction with microsatellite markers and then screened for transposable repeat elements. Results: The severity of clinical presentation is correlated with SNCA dosage and does not appear to be overtly affected by the presence of other genes in the multiplicated region. With the exception of the Lister kindred, in each family the multiplication event appears de novo. The type and position of Alu/LINE repeats are also different at each breakpoint. Microsatellite analysis demonstrates two genomic mechanisms are responsible for chromosome 4q21 multiplications, including both SNCA duplication and recombination. Interpretation: SNCA dosage is responsible for parkinsonism, autonomic dysfunction, and dementia observed within each family. We hypothesize dysregulated expression of wild-type (alpha-synuclein results in parkinsonism and may explain the recent association of common SNCA variants in sporadic Parkinson's disease. SNCA genomic duplication results from intraallelic (segmental duplication) or interallelic recombination with unequal crossing over, whereas both mechanisms appear to be required for genomic SNCA triplication. C1 [Farrer, Matthew J.] Mayo Clin, Morris K Udall Parkinson Dis Res Ctr Excellence, Dept Neurosci, Coll Med,Div Neurogenet, Jacksonville, FL 32224 USA. [Middleton, Frank A.] SUNY Upstate Med Univ, Microarray Core Facil, Ctr Neuropsychiatr Genet, Syracuse, NY USA. [Nishioka, Kenya] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. [Fuchs, Julia; Gasser, Thomas] Univ Tubingen, Hertie Inst Clin Brain Res, Ctr Neurol, Dept Neurodegenerat Dis, Tubingen, Germany. [Maraganore, Demetrius M.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. [Adler, Charles H. .] Mayo Clin, Coll Med, Dept Neurol, Scottsdale, AZ USA. [Larvor, Lydie; Chartier-Harlin, Marie-Christine] IRCL, MENRT, EA2683, Lille, France. [Nilsson, Christer] Lund Univ, Dept Clin Med, Div Geriatr Psychiat, Lund, Sweden. [Langston, J. William] Parkinson Inst, Sunnyvale, CA USA. [Langston, J. William] Ctr Clin, Sunnyvale, CA USA. [Gwinn, Katrina] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Farrer, MJ (reprint author), Mayo Clin, Morris K Udall Parkinson Dis Res Ctr Excellence, Dept Neurosci, Coll Med,Div Neurogenet, 4500 San Pablo Road S, Jacksonville, FL 32224 USA. EM farrer.matthew@mayo.edu RI Gwinn, Katrina/C-2508-2009; Ross, Owen/D-7573-2013; LICEND, CEMND/F-1296-2015; Braithwaite, Adam/R-4099-2016; OI Braithwaite, Adam/0000-0003-3228-2172; Skipper, Lisa/0000-0002-1524-9787; Gwinn, Katrina/0000-0002-8277-651X FU NIA NIH HHS [P01 AG017216-05, P01 AG017216, P01 AG017216-09, P01 AG017216-090005, P01 AG17216]; NINDS NIH HHS [N01-NS-2-2349, P01 NS040256, P50 #NS40256, P50 NS040256] NR 43 TC 142 Z9 143 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2008 VL 63 IS 6 BP 743 EP 750 DI 10.1002/ana.21380 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 321HA UT WOS:000257294100007 PM 18571778 ER PT J AU Yaffe, K Lindquist, K Shlipak, MG Simonsick, E Fried, L Rosano, C Satterfield, S Atkinson, H Windham, BG Kurella-Tamura, M AF Yaffe, Kristine Lindquist, Karla Shlipak, Michael G. Simonsick, Eleanor Fried, Linda Rosano, Caterina Satterfield, Suzanne Atkinson, Hal Windham, B. Gwen Kurella-Tamura, Manjula CA Hlth ABC Study TI Cystatin C as a marker of cognitive function in elders: Findings from the Health ABC study SO ANNALS OF NEUROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; ONSET ALZHEIMER-DISEASE; OLDER-ADULTS; FOLLOW-UP; IMPAIRMENT; RISK; ASSOCIATION; HEART AB We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain P-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p <= 0.02) compared with those with intermediate/low level and 7 years greater decline (p <= 0.04). Incident cognitive impairment (decline >= 1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15). C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94121 USA. [Lindquist, Karla; Shlipak, Michael G.; Kurella-Tamura, Manjula] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. [Simonsick, Eleanor; Windham, B. Gwen] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Fried, Linda] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Atkinson, Hal] Wake Forest Univ, Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. [Yaffe, Kristine; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014; OI Kurella Tamura, Manjula/0000-0001-5227-2479; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Intramural NIH HHS; NIA NIH HHS [N01 AG062103, AG-6-2101, AG-6-2103, AG-6-2106, AG021918, N01 AG062101, N01 AG062106, R01 AG021918, R01 AG021918-01A1]; NIDDK NIH HHS [DK069406, R01 DK069406, R01 DK069406-01A1] NR 20 TC 40 Z9 47 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2008 VL 63 IS 6 BP 798 EP 802 DI 10.1002/ana.21383 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 321HA UT WOS:000257294100014 PM 18496846 ER PT J AU Dunleavy, K Little, RF Pittaluga, S Grant, N Shovlin, M Steinberg, S Yarchoan, R Janik, J Jaffe, ES Wilson, WH AF Dunleavy, K. Little, R. F. Pittaluga, S. Grant, N. Shovlin, M. Steinberg, S. Yarchoan, R. Janik, J. Jaffe, E. S. Wilson, W. H. TI A prospective study of dose-adjusted (DA) epoch with rituximab in adults with newly diagnosed burkitt lymphoma: A regimen with high efficacy and low toxicity SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Dunleavy, K.; Little, R. F.; Pittaluga, S.; Grant, N.; Shovlin, M.; Steinberg, S.; Yarchoan, R.; Janik, J.; Jaffe, E. S.; Wilson, W. H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 83 EP 84 PG 2 WC Oncology SC Oncology GA 312TK UT WOS:000256693500025 ER PT J AU O'Mahony, D Janik, JE Carrasquillo, JA Paik, CH Fioravanti, S Whatley, M Pittaluga, S Brechbiel, MW Morris, JC Waldmann, A AF O'Mahony, D. Janik, J. E. Carrasquillo, J. A. Paik, C. H. Fioravanti, S. Whatley, M. Pittaluga, S. Brechbiel, M. W. Morris, J. C. Waldmann, A. TI Phase I/II study of yttrium-90 labeled humanized anti-tac (HAT) monoclonal antibody and calcium DTPA in cd25-expressing malignancies other than adult T-cell leukemia SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [O'Mahony, D.; Janik, J. E.; Fioravanti, S.; Morris, J. C.; Waldmann, A.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Pittaluga, S.] NIH, Pathol Lab, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 1 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 JUN PY 2008 VL 19 SU 4 BP 88 EP 88 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500035 ER PT J AU Lenz, G Wright, G Dave, S Kohlmann, A Xiao, W Powell, J Zhao, H Xu, W Gascoyne, RD Connors, JM May, L Iqbal, J Vose, J Weisenburger, D Greiner, T Armitage, O Bast, M Fu, K Campo, E Montserrat, E Lopez-Guillermo, A Jares, P Martinez, A Rimsza, LM Fisher, RI Braziel, RM Tubbs, R Miller, T Cook, J Pohlman, B Sweetenham, J Troen, G Smeland, EB Delabie, J Kvaloy, S Holte, H Dierickx, D Verhoef, G Jaffe, ES Wilson, WH Hartmann, E Rosenwald, A Ott, G Muller-Hermelink, HK Wrench, D Lister, TA Williams, M Wieczorek, L Chan, WC Staudt, LM AF Lenz, G. Wright, G. Dave, S. Kohlmann, A. Xiao, W. Powell, J. Zhao, H. Xu, W. Gascoyne, R. D. Connors, J. M. May, L. Iqbal, J. Vose, J. Weisenburger, D. Greiner, T. Armitage, O. Bast, M. Fu, K. Campo, E. Montserrat, E. Lopez-Guillermo, A. Jares, P. Martinez, A. Rimsza, L. M. Fisher, R. I. Braziel, R. M. Tubbs, R. Miller, T. Cook, J. Pohlman, B. Sweetenham, J. Troen, G. Smeland, E. B. Delabie, J. Kvaloy, S. Holte, H. Dierickx, D. Verhoef, G. Jaffe, E. S. Wilson, W. H. Hartmann, E. Rosenwald, A. Ott, G. Muller-Hermelink, H. K. Wrench, D. Lister, T. A. Williams, M. Wieczorek, L. Chan, W. C. Staudt, L. M. TI Gene expression signatures predict survival in diffuse large B cell lymphoma following rituximab and CHOP-like chemotherapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Lenz, G.; Staudt, L. M.] NCI, CCR, Bethesda, MD 20892 USA. [Williams, M.; Wieczorek, L.] Roche, Mol Syst, Pleasanton, CA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 93 EP 93 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500050 ER PT J AU Dunleavy, K Pittaluga, S Janik, J Grant, N Shovlin, M Steinberg, S Raffeld, M Jaffe, ES Staudt, LM Wilson, WH AF Dunleavy, K. Pittaluga, S. Janik, J. Grant, N. Shovlin, M. Steinberg, S. Raffeld, M. Jaffe, E. S. Staudt, L. M. Wilson, W. H. TI The addition of rituximab to dose-adjusted (DA)epoch obviates the need for radiation in the treatment of primary mediastinal large B-cell lymphoma (PMBL): A prospective study of 58 patients SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Dunleavy, K.; Pittaluga, S.; Janik, J.; Grant, N.; Shovlin, M.; Steinberg, S.; Raffeld, M.; Jaffe, E. S.; Staudt, L. M.; Wilson, W. H.] Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 96 EP 96 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500059 ER PT J AU Lenz, G Wright, G Dave, S Emre, NT Davis, RE Carty, S Lam, LT Shaffer, AL Xiao, W Powell, J Rosenwald, A Ott, G Muller-Hermelink, HK Gascoyne, RD Connors, JM Campo, E Jaffe, ES Delabie, J Smeland, EB Rimsza, LM Fisher, RI Weisenburger, D Chan, WC Staudt, LM AF Lenz, G. Wright, G. Dave, S. Emre, N. T. Davis, R. E. Carty, S. Lam, L. T. Shaffer, A. L. Xiao, W. Powell, J. Rosenwald, A. Ott, G. Muller-Hermelink, H. K. Gascoyne, R. D. Connors, J. M. Campo, E. Jaffe, E. S. Delabie, J. Smeland, E. B. Rimsza, L. M. Fisher, R. I. Weisenburger, D. Chan, W. C. Staudt, L. M. TI Gene expression subtypes of diffuse large B cell lymphoma arise by distinct genetic pathways SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Lenz, G.; Staudt, L. M.] NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 99 EP 99 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500066 ER PT J AU Jaffe, ES Feldman, AL Arber, DA Pittaluga, S Martinez, A Camos, M Burke, J Raffeld, M Warnke, R AF Jaffe, E. S. Feldman, A. L. Arber, D. A. Pittaluga, S. Martinez, A. Camos, M. Burke, J. Raffeld, M. Warnke, R. TI Histiocytic/dendritic sarcomas clonally related to follicular lymphoma: Evidence for lineage plasticity in mature human B-cells SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Jaffe, E. S.; Feldman, A. L.; Pittaluga, S.; Raffeld, M.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [Arber, D. A.; Warnke, R.] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. [Martinez, A.; Camos, M.] Univ Barcelona, Dept Pathol, Barcelona, Spain. [Burke, J.] Alta Bates Summit Med Ctr, Dept Pathol, Berkeley, CA USA. RI Feldman, Andrew/D-5028-2012 NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 105 EP 105 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500087 ER PT J AU Cerhan, J Natkunam, Y Morton, L Maurer, M Habermann, T Chanock, S Cozen, W Lynch, C Severson, R Allmer, C Lossos, I Levy, R Rothman, N Slager, S Hartge, P Dogan, A Wang, S AF Cerhan, J. Natkunam, Y. Morton, L. Maurer, M. Habermann, T. Chanock, S. Cozen, W. Lynch, C. Severson, R. Allmer, C. Lossos, I. Levy, R. Rothman, N. Slager, S. Hartge, P. Dogan, A. Wang, S. TI LMO2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma (DLBCL) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Cerhan, J.; Maurer, M.; Habermann, T.; Allmer, C.; Slager, S.; Dogan, A.] Mayo Clin, Rochester, MN USA. [Natkunam, Y.; Levy, R.] Stanford Univ, Stanford, CA 94305 USA. [Morton, L.; Chanock, S.; Rothman, N.; Hartge, P.; Wang, S.] NCI, Bethesda, MD 20892 USA. [Cozen, W.] USC, Los Angeles, CA USA. [Lynch, C.] Univ Iowa, Iowa City, IA USA. [Severson, R.] Wayne State, Detroit, MI USA. [Lossos, I.] Univ Miami, Miami, FL USA. RI Slager, Susan/B-6756-2009 NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 107 EP 107 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500092 ER PT J AU Ngoma, T Kaijage, J Githang'a, J Durosinmi, M Adeodu, O Salawu, L Aken'Ova, Y Brown, B Rohatiner, AZS Venzon, D Adde, M Magrath, IT AF Ngoma, T. Kaijage, J. Githang'a, J. Durosinmi, M. Adeodu, O. Salawu, L. Aken'Ova, Y. Brown, B. Rohatiner, A. Z. S. Venzon, D. Adde, M. Magrath, I. T. TI A multi-centre study of the treatment and characterisation of Burkitt lymphoma in 4 African countries SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Rohatiner, A. Z. S.; Adde, M.; Magrath, I. T.] INCTR, Brussels, Belgium. [Ngoma, T.; Kaijage, J.] ORCI, Dar Es Salaam, Tanzania. [Githang'a, J.] Kenyatta Natl Hosp, Nairobi, Kenya. [Durosinmi, M.; Adeodu, O.; Salawu, L.; Brown, B.] OAUTHC, Ife, Nigeria. [Aken'Ova, Y.; Brown, B.] UCH, Ibadan, Nigeria. [Venzon, D.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 JUN PY 2008 VL 19 SU 4 BP 108 EP 108 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500096 ER PT J AU O'Connor, O Czuczman, MS LaCasce, A Gerecitano, J Leonard, JP Dunleavy, K Krivoshik, A Shovlin, M Narwal, A Xiong, H Chiu, Y Wilson, W AF O'Connor, O. Czuczman, M. S. LaCasce, A. Gerecitano, J. Leonard, J. P. Dunleavy, K. Krivoshik, A. Shovlin, M. Narwal, A. Xiong, H. Chiu, Y. Wilson, W. TI A phase 1 study evaluating the safety, PK & efficacy of ABT-263 in subjects with refractory or relapsed lymphoid malignancies SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [O'Connor, O.; Narwal, A.] Columbia Univ, Irving Canc Res Ctr, New York, NY 10027 USA. [Czuczman, M. S.] Roswell Pk Canc Inst, Lymphoma Myeloma Serv, Buffalo, NY 14263 USA. [LaCasce, A.] Dana Farber Canc Inst, Lymphoma Program, Boston, MA 02115 USA. [Gerecitano, J.] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, New York, NY 10021 USA. [Leonard, J. P.] Cornell Univ, Weill Cornell Med Coll, Ithaca, NY 14853 USA. [Dunleavy, K.; Shovlin, M.; Wilson, W.] NCI, NIH, Bethesda, MD 20892 USA. [Krivoshik, A.; Xiong, H.; Chiu, Y.] Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 115 EP 116 PG 2 WC Oncology SC Oncology GA 312TK UT WOS:000256693500118 ER PT J AU Staudt, LM AF Staudt, L. M. TI RNA interference-based genetic screening meets cancer genome resequencing SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Staudt, L. M.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 117 EP 117 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500121 ER PT J AU Zhang, J Jima, D Fischer, R Jacobs, C Lugar, P Lipsky, P Dave, SS AF Zhang, J. Jima, D. Fischer, R. Jacobs, C. Lugar, P. Lipsky, P. Dave, S. S. TI Concomitant gene expression profiling and microRNA profiling reveal a role for microRNAs in B cell development and lymphomas at every stage SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Dave, S. S.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27706 USA. [Zhang, J.; Jima, D.; Jacobs, C.] Duke Univ, IGSP, Durham, NC 27706 USA. [Fischer, R.; Lipsky, P.] NIAMS, NIH, Bethesda, MD USA. [Lugar, P.] Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 117 EP 117 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500124 ER PT J AU Wilson, WH AF Wilson, W. H. TI CNS involvement in lymphomas SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Wilson, W. H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 118 EP 118 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500126 ER PT J AU Harris, NL Swerdlow, S Campo, E Jaffe, ES Stein, H Pileri, S Thiele, J Vardiman, J AF Harris, N. L. Swerdlow, S. Campo, E. Jaffe, E. S. Stein, H. Pileri, S. Thiele, J. Vardiman, J. TI The World Health Organization (WHO) classification of lymphoid neoplasms: What's new? SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Harris, N. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Swerdlow, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Campo, E.] Univ Barcelona, Barcelona, Spain. [Jaffe, E. S.] NCI, Bethesda, MD 20892 USA. [Stein, H.] Free Univ Berlin, D-1000 Berlin, Germany. [Pileri, S.] Univ Bologna, Bologna, Italy. [Thiele, J.] Univ Cologne, Cologne, Germany. [Vardiman, J.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 7 Z9 7 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 119 EP 119 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500129 ER PT J AU Domingo-Domenech, E Benavente, Y Font, R Montalban, C Bosch, R Gonzalez-Barca, E Guma, J Wang, S de Sevilla, AF Rothman, N de Sanjose, S AF Domingo-Domenech, E. Benavente, Y. Font, R. Montalban, C. Bosch, R. Gonzalez-Barca, E. Guma, J. Wang, S. de Sevilla, A. Fernandez Rothman, N. de Sanjose, S. TI Family history of cancer and risk of lymphoma: Influence of IL8RB, MTHFR and IL10 polymorphisms SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Wang, S.; Rothman, N.] Natl Canc Inst, Bethesda, MD USA. [Guma, J.] Hosp St Joan, Reus, Spain. [Bosch, R.] Hosp Verge Cinta, Tortosa, Spain. [Montalban, C.] Hosp Ramon & Cajal, E-28034 Madrid, Spain. RI de Sanjose Llongueras, Silvia/H-6339-2014; Benavente, Yolanda/H-9810-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 131 EP 131 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500165 ER PT J AU Kristinsson, SY Bjorkholm, M Goldin, LR McMaster, ML Turesson, I Landgren, O AF Kristinsson, S. Y. Bjorkholm, M. Goldin, L. R. McMaster, M. L. Turesson, I. Landgren, O. TI Familial characteristics of Waldenstrom's macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL): A population-based study in Sweden SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Kristinsson, S. Y.; Bjorkholm, M.; Landgren, O.] Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden. [Goldin, L. R.; McMaster, M. L.] NCI, NIH, Bethesda, MD 20892 USA. [Turesson, I.] Malmo Univ Hosp, Dept Med, Malmo, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 166 EP 166 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500291 ER PT J AU Wiestner, A Vire, B Njuguna, N Soto, S Boss, C Pittaluga, S Aue, G AF Wiestner, A. Vire, B. Njuguna, N. Soto, S. Boss, C. Pittaluga, S. Aue, G. TI Lenalidomide leads to a pro-inflammatory cytokine release syndrome in CLL: Implications for patient management and a possible role of innate immunity SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Wiestner, A.; Vire, B.; Njuguna, N.; Soto, S.; Boss, C.; Aue, G.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Pittaluga, S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 194 EP 194 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500395 ER PT J AU McGowan, PM McKiernan, E Bolster, F Ryan, BM Hill, ADK McDermott, EW Evoy, D O'Higgins, N Crown, J Duffy, MJ AF McGowan, P. M. McKiernan, E. Bolster, F. Ryan, B. M. Hill, A. D. K. McDermott, E. W. Evoy, D. O'Higgins, N. Crown, J. Duffy, M. J. TI ADAM-17 predicts adverse outcome in patients with breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE ADAM-17; breast cancer; metalloproteinases; prognosis ID SELECTIVE-INHIBITION; GROWTH-FACTOR; ALPHA; CELLS; EGFR; TRASTUZUMAB; THERAPY; TACE; METALLOPROTEASES; RECEPTORS AB ADAM-17 is a matrix metalloproteinase-like enzyme involved in the release of several ligands that have been shown to promote both cancer formation and progression. These ligands include transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, epiregulin and tumor necrosis factor-alpha. In this investigation, we measured the expression of total ADAM-17 by enzyme-linked immunosorbent assay in 153 invasive breast cancers. We also measured the precursor and active forms by western blotting in 140 invasive breast cancers. Expression of ADAM-17 was significantly increased in high-grade compared with low-grade tumors and was independent of tumor size, lymph node metastasis and estrogen receptor status. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for breast cancer. Our results are further evidence that ADAM-17 is involved in breast cancer progression and thus provides further impetus for exploiting ADAM-17 as new target for cancer treatment. C1 [McGowan, P. M.; McKiernan, E.; Bolster, F.; Ryan, B. M.; Hill, A. D. K.; McDermott, E. W.; Evoy, D.; O'Higgins, N.; Duffy, M. J.] Univ Coll Dublin, Conway Inst, Dept Pathol, Dublin 4, Ireland. [McGowan, P. M.; McKiernan, E.; Bolster, F.; Ryan, B. M.; Hill, A. D. K.; McDermott, E. W.; Evoy, D.; O'Higgins, N.; Duffy, M. J.] Univ Coll Dublin, Conway Inst, Sch Med & Med Sci, Dublin 4, Ireland. [Ryan, B. M.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Canc Prevent Div,NIH, Bethesda, MD 20892 USA. RP Duffy, MJ (reprint author), St Vincents Univ Hosp, Nucl Med Lab, Dublin 4, Ireland. EM michael.j.duffy@ucd.ie OI McGowan, Patricia/0000-0003-3936-2503 NR 30 TC 45 Z9 47 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 IS 6 BP 1075 EP 1081 DI 10.1093/annonc/mdm609 PG 7 WC Oncology SC Oncology GA 306SM UT WOS:000256268100007 PM 18238782 ER PT J AU Zhao, YC Yang, S AF Zhao, Yichuan Yang, Song TI Empirical likelihood inference for censored median regression with weighted empirical hazard functions SO ANNALS OF THE INSTITUTE OF STATISTICAL MATHEMATICS LA English DT Article DE confidence region; conditional Kaplan-Meier estimator; martingale; counting process; right censoring; weighted empirical processes ID LINEAR-REGRESSION; CONFIDENCE BANDS; SURVIVAL FUNCTIONS; SEMIPARAMETRIC ANALYSIS; RANK-TESTS; MODELS; QUANTILES; RATIOS; SAMPLE; TERM AB In recent years, median regression models have been shown to be useful for analyzing a variety of censored survival data in clinical trials. For inference on the regression parameter, there have been a variety of semiparametric procedures. However, the accuracy of such procedures in terms of coverage probability can be quite low when the censoring rate is heavy. In this paper, based on weighted empirical hazard functions, we apply an empirical likelihood (EL) ratio method to the median regression model with censoring data and derive the limiting distribution of EL ratio. Confidence region for the regression parameter can then be obtained accordingly. Furthermore, we compared the proposed method with the standard method through extensive simulation studies. The proposed method almost always outperformed the existing method. C1 [Zhao, Yichuan] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. [Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zhao, YC (reprint author), Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. EM yzhao@mathstat.gsu.edu NR 42 TC 3 Z9 3 U1 5 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0020-3157 J9 ANN I STAT MATH JI Ann. Inst. Stat. Math. PD JUN PY 2008 VL 60 IS 2 BP 441 EP 457 DI 10.1007/s10463-006-0110-4 PG 17 WC Statistics & Probability SC Mathematics GA 302VE UT WOS:000255997100010 ER PT J AU Louie, GH Chitkara, P Ward, MM AF Louie, G. H. Chitkara, P. Ward, M. M. TI Relapse of sarcoidosis upon treatment with etanercept SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Letter ID TUMOR-NECROSIS-FACTOR; PULMONARY SARCOIDOSIS; INFLIXIMAB THERAPY; FACTOR-ALPHA C1 [Louie, G. H.; Chitkara, P.; Ward, M. M.] NIAMSD, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural NIH HHS NR 11 TC 25 Z9 25 U1 0 U2 1 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 JUN PY 2008 VL 67 IS 6 BP 896 EP 898 DI 10.1136/ard.2007.078840 PG 5 WC Rheumatology SC Rheumatology GA 299SD UT WOS:000255774400032 PM 18474661 ER PT J AU Nakata, H Steinberg, SM Koh, Y Maeda, K Takaoka, Y Tarnarnura, H Fujii, N Mitsuya, H AF Nakata, Hirotorno Steinberg, Seth M. Koh, Yasuhiro Maeda, Kenji Takaoka, Yoshikazu Tarnarnura, Hirokazu Fujii, Nobutaka Mitsuya, Hiroaki TI Potent synergistic anti-human immunodeficiency virus (HIV) effects using combinations of the CCR5 inhibitor aplaviroc with other anti-HIV drugs SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CHEMOKINE RECEPTOR CCR5; SCH-C SCH-351125; IN-VITRO; SMALL-MOLECULE; HIGHLY POTENT; 3-DIMENSIONAL ANALYSIS; TYPE-1 INFECTION; CXCR4 INHIBITORS; MIP-1 ALPHA; ANTAGONIST AB Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents, including four U.S. Food and Drug Administration-approved drugs, two CCR5 inhibitors (TAK779 and SCH-C) and two CXCR4 inhibitors (AMD3100 and TE14011). Combination effects were defined as synergistic or antagonistic when the activity of drug A combined with B was statistically greater or less, respectively, than the additive effects of drugs A and A combined and drugs B and B combined by using the Combo method, described in this paper, which provides (i) a flexible choice of interaction models and (ii) the use of nonparametric statistical methods. Synergistic effects against R5-HIV-1(Ba-L), and a 50:50 mixture of R5-HIV-1(Ba-L) and X4-HIV-1(ERS104pre) (HIV-1(Ba-L/104pre)) were seen when AVC was combined with zidovudine, nevirapine, indinavir, or enfuvirtide. Mild synergism and additivity were observed when AVC was combined with TAK779 and SCH-C, respectively. We also observed more potent synergism against HIV-1(Ba-L/104pre) when AVC was combined with AMD3100 or TE14011. The data demonstrate a tendency toward greater synergism with AVC plus either of the two CXCR4 inhibitors compared to the synergism obtained with combinations of AVC and other drugs, suggesting that the development of effective CXCR4 inhibitors may be important for increasing the efficacies of CCR5 inhibitors. C1 [Nakata, Hirotorno; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan. [Nakata, Hirotorno; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan. [Nakata, Hirotorno; Maeda, Kenji; Mitsuya, Hiroaki] NCI, Ctr Canc Res, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch,NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Takaoka, Yoshikazu] Ono Pharmaceut Co Ltd, Osaka 6188585, Japan. [Tarnarnura, Hirokazu; Fujii, Nobutaka] Kyoto Univ, Sakyo Ku, Grad Sch Pharmaceut Sci, Kyoto 6068501, Japan. RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hm21q@nih.gov FU Intramural NIH HHS NR 42 TC 21 Z9 23 U1 0 U2 4 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 JUN PY 2008 VL 52 IS 6 BP 2111 EP 2119 DI 10.1128/AAC.01.299-07 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 306UG UT WOS:000256272700028 PM 18378711 ER PT J AU Stergiopoulou, T Meletiadis, J Sein, T Papaioannidou, P Tsiouris, I Roilides, E Walsh, TJ AF Stergiopoulou, Theodouli Meletiadis, Joseph Sein, Tin Papaioannidou, Paraskevi Tsiouris, Ioannis Roilides, Emmanuel Walsh, Thomas J. TI Isobolographic analysis of pharmacodynamic interactions between antifungal agents and ciprofloxacin against Candida albicans and Aspergillus fumigatus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B; IN-VITRO; ANTIEPILEPTIC DRUGS; PATHOGENIC FUNGI; COMBINATION; MODEL; MICE; QUINOLONES; SYNERGY AB Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 mu g/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis. C1 [Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Roilides, Emmanuel; Walsh, Thomas J.] NCI, Pediat Oncol Branch, NIH, Immunocompromised Host Sect, Bethesda, MD 20892 USA. [Sein, Tin] SAIC Frederick Inc, Frederick, MD 21702 USA. [Stergiopoulou, Theodouli; Papaioannidou, Paraskevi] Aristotle Univ Thessaloniki, Fac Med, Dept Pharmacol, GR-54006 Thessaloniki, Greece. [Tsiouris, Ioannis; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54006 Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, NIH, Immunocompromised Host Sect, 10 Ctr Dr,Bldg 10,Rm 1-5888, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Papaioannidou, Paraskevi/D-9864-2011; OI Papaioannidou, Paraskevi/0000-0001-8880-0288 FU Intramural NIH HHS NR 43 TC 20 Z9 20 U1 0 U2 2 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 JUN PY 2008 VL 52 IS 6 BP 2196 EP 2204 DI 10.1128/AAC.00735-07 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 306UG UT WOS:000256272700039 PM 18299413 ER PT J AU Moayeri, M Robinson, TA Leppla, SH Karginov, VA AF Moayeri, Mahtab Robinson, Tanisha A. Leppla, Stephen H. Karginov, Vladimir A. TI In vivo efficacy of beta-cyclodextrin derivatives against anthrax lethal toxin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODIES; GUINEA-PIGS; INFECTION; MICE; CIPROFLOXACIN; CHALLENGE; TOXICITY; IMMUNITY AB We evaluated the in vivo efficacy of three beta-cyclodextrin derivatives that block the anthrax protective antigen pore. These compounds were at least 15-fold more potent than previously described beta-cyclodextrins in protecting against anthrax lethal toxin in a rat model. One of the drugs was shown to protect mice from bacterial infection. C1 [Robinson, Tanisha A.; Karginov, Vladimir A.] Innovat Biol Inc, Herndon, VA 20171 USA. [Moayeri, Mahtab; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Karginov, VA (reprint author), Innovat Biol Inc, 13455 Sunrise Valley Dr,Suite 200, Herndon, VA 20171 USA. EM vak@innovbio.com FU Intramural NIH HHS; NIAID NIH HHS [R44 AI052894, 2R44AI052894-02] NR 16 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 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2008 VL 52 IS 6 BP 2239 EP 2241 DI 10.1128/AAC.00009-08 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 306UG UT WOS:000256272700047 PM 18378717 ER PT J AU Jonmarker, S Glaessgen, A Culp, WD Pisa, P Lewensohn, R Ekman, P Valdman, A Egevad, L AF Jonmarker, Sara Glaessgen, Axel Culp, W. David Pisa, Pavel Lewensohn, Rolf Ekman, Peter Valdman, Alexander Egevad, Lars TI Expression of PDX-1 in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic tissue SO APMIS LA English DT Article DE adenocarcinoma of the prostate; PDX-1; immunohistochemistry; tissue microarray ID PANCREATIC-ISLET CELLS; SOMATOSTATIN RECEPTORS; DIABETES-MELLITUS; TRANSCRIPTION; RISK; HOMEOBOX-1; DUODENUM; GENE AB Pancreatic duodenal homeobox 1 (PDX-1), a Hox type transcription factor, is necessary for differentiation of exocrine and endocrine pancreas, and regulates insulin gene transcription. PDX-1 expression was studied by immunohistochemistry on a tissue microarray (TMA) of 289 primary prostate cancers (PCa) from radical prostatectomy (RP) specimens with median follow-up of 48.9 months. We separately arrayed benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa from 40 men and also 17 lymph node metastases. Intensity and extent of immunoreactivity and their product (IRp) were evaluated by two independent observers. PDX-1 was overexpressed in cancer vs benign tissue (p<0.001), but also in atrophy and HGPIN vs cancer (p<0.001 and p=0.022, respectively). PDX-1 expression did not correlate with biochemical recurrence, but decreased with higher Gleason pattern (p<0.001) and in metastases vs primary PCa (p<0.001). Weighted kappa for interobserver agreement of intensity, extent and IRp was 0.65, 0.13 and 0.54, respectively. Presence of PDX-1 protein in benign and malignant prostatic tissue was confirmed by Western blot. In view of recent attention to the role of insulin systems in men with PCa, this protein is of interest in the pathogenesis of PCa. C1 [Jonmarker, Sara; Glaessgen, Axel; Culp, W. David; Pisa, Pavel; Lewensohn, Rolf; Valdman, Alexander] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Culp, W. David] NIH, Bethesda, MD 20892 USA. [Egevad, Lars] Int Agcy Res Canc, F-69372 Lyon, France. [Ekman, Peter] Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden. RP Jonmarker, S (reprint author), Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. NR 26 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0903-4641 EI 1600-0463 J9 APMIS JI APMIS PD JUN PY 2008 VL 116 IS 6 BP 491 EP 498 DI 10.1111/j.1600-0463.2008.01020.x PG 8 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 329IJ UT WOS:000257861000006 PM 18754323 ER PT J AU Hong, DS Reddy, SB Prieto, VG Wright, JJ Tannir, NM Cohen, PR Diwan, AH Evans, HL Kurzrock, R AF Hong, David S. Reddy, Srini B. Prieto, Victor G. Wright, John J. Tannir, Nizar M. Cohen, Philip R. Diwan, A. Hafeez Evans, Harry L. Kurzrock, Razelle TI Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MYELODYSPLASTIC SYNDROME; INHIBITOR; R115777; CANCER AB Background: Keratoacanthomas, as well as an actinic keratosis progressing to squamous cell cancer, have been reported in patients who were treated with sorafenib, a multikinase inhibitor known to suppress the actions of Raf kinase and vascular endothelial growth factor receptor. Observations: We describe a 70-year-old white woman with metastatic renal cell carcinoma who was treated with a combination of sorafenib and tipifarnib (a farnesyltransferase inhibitor). She had no history of skin cancer. However, within 3 months after starting this therapy, she developed 3 erythematous nodules on her legs. Pathologic examination showed deeply invasive, well-differentiated squamous cell carcinomas. The tumors were excised, and sorafenib-tipifarnib treatment was discontinued. No new lesions have developed to date. Conclusions: Targeted agents, such as sorafenib and tipifarnib, are increasingly being used in the management of visceral malignant neoplasms. A temporal relationship was observed between the initiation of the targeted treatments and the emergence of these cutaneous cancers. Further study of the mechanisms responsible for the rapid appearance of squamous cell cancers in this setting may provide insights into the pathogenesis of skin tumors. C1 [Hong, David S.] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Div Canc Med, Phase Program 1,Unit 455, Houston, TX 77030 USA. [Prieto, Victor G.; Diwan, A. Hafeez; Evans, Harry L.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Prieto, Victor G.; Diwan, A. Hafeez] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA. [Tannir, Nizar M.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Wright, John J.] NCI, Bethesda, MD 20892 USA. [Cohen, Philip R.] Univ Houston, Ctr Hlth, Dept Dermatol, Houston, TX 77004 USA. [Cohen, Philip R.] Univ Texas Houston, Sch Med, Dept Dermatol, Houston, TX USA. RP Hong, DS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Div Canc Med, Phase Program 1,Unit 455, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dshong@mdanderson.org FU NCI NIH HHS [5 UO1 CA062461]; PHS HHS [TRI 25XS068] NR 18 TC 37 Z9 38 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2008 VL 144 IS 6 BP 779 EP 782 DI 10.1001/archderm.144.6.779 PG 4 WC Dermatology SC Dermatology GA 314FZ UT WOS:000256796200011 PM 18559769 ER PT J AU Kong, HH Sibaud, V Turner, MLC Fojo, T Hornyak, TJ Chevreau, C AF Kong, Heidi H. Sibaud, Vincent Turner, Maria L. Chanco Fojo, Tito Hornyak, Thomas J. Chevreau, Christine TI Sorafenib-induced eruptive melanocytic lesions SO ARCHIVES OF DERMATOLOGY LA English DT Letter ID NEVI; THERAPY C1 [Kong, Heidi H.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Kong, HH (reprint author), NCI, Dermatol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 12N238,MSC 1908, Bethesda, MD 20892 USA. EM konghe@mail.nih.gov RI Sibaud, Vincent/P-6270-2014; Chevreau, Christine/A-5565-2015; OI Sibaud, Vincent/0000-0003-2585-6633; Kong, Heidi/0000-0003-4424-064X FU Intramural NIH HHS [Z99 CA999999] NR 7 TC 46 Z9 46 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2008 VL 144 IS 6 BP 820 EP 822 DI 10.1001/archderm.144.6.820 PG 4 WC Dermatology SC Dermatology GA 314FZ UT WOS:000256796200032 PM 18559790 ER PT J AU Uhl, GR Liu, QR Drgon, T Johnson, C Walther, D David, SP Niaura, R Lerman, C Rose, E AF Uhl, George R. Liu, Qing-Rong Drgon, Tomas Johnson, Catherine Walther, Donna David, Sean P. Niaura, Ray Lerman, Caryn Rose, E. TI Molecular genetics of successful smoking cessation - Convergent genome-wide association study results SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NICOTINE REPLACEMENT THERAPY; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-I; T-CADHERIN; ENVIRONMENTAL-INFLUENCES; VULNERABILITY LOCI; TOBACCO DEPENDENCE; CLINICAL-TRIAL; RECEPTOR DRD2; SUBSTANCE USE AB Context: Smoking remains a major public health problem. Twin studies indicate that the ability to quit smoking is substantially heritable, with genetics that overlap modestly with the genetics of vulnerability to dependence on addictive substances. Objectives: To identify replicated genes that facilitate smokers' abilities to achieve and sustain abstinence from smoking (hereinafter referred to as quit-success genes) found in more than 2 genome-wide association (GWA) studies of successful vs unsuccessful abstainers, and, secondarily, to nominate genes for selective involvement in smoking cessation success with bupropion hydrochloride vs nicotine replacement therapy (NRT). Design: The GWA results in subjects From 3 centers, with secondary analyses of NRT vs bupropion responders. Setting: Outpatient smoking cessation trial participants from 3 centers. Participants: European American smokers who successfully vs unsuccessfully abstain from smoking with biochemical confirmation in a smoking cessation trial using NRT, bupropion, or placebo (N = 550). Main Outcome Measures: Quit-success genes, reproducibly identified by clustered nominally positive single-nucleotide polymorphisms (SNPs) in more than 2 independent samples with significant P values based on Monte Carlo simulation trials. The NRT-selective genes were nominated by clustered SNPs that display much larger t values for NRT vs placebo comparisons. The bupropion-selective genes were nominated by bupropion-selective results. Results: Variants in quit-success genes are likely to alter cell adhesion, enzymatic, transcriptional, structural, and DNA, RNA, and/or protein-handling functions. Quit-success genes are identified by clustered nominally positive SNPs from more than 2 samples and are unlikely to represent chance observations (Monte Carlo P<.0003). These genes display modest overlap with genes identified in GWA studies of dependence on addictive substances and memory. Conclusions: These results support polygenic genetics for success in abstaining from smoking, overlap with genetics of substance dependence and memory, and nominate gene variants for selective influences on therapeutic responses to bupropion vs NRT. Molecular genetics should help match the types and/or intensity of anti-smoking treatments with the smokers most likely to benefit from them. C1 [Uhl, George R.; Liu, Qing-Rong; Drgon, Tomas; Johnson, Catherine; Walther, Donna] Natl Inst Drug Abuse, Mol Neurobiol Branch, Natl Inst Hlth, Intramural Res Program, Baltimore, MD 21224 USA. [Rose, E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [David, Sean P.] Brown Univ, Dept Family Med, Warren Alpert Med Sch, Pawtucket, RI USA. [Niaura, Ray] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Pawtucket, RI USA. [Niaura, Ray] Butler Hosp, Transdisciplinary Res Grp, Providence, RI 02906 USA. [Lerman, Caryn] Univ Penn, Dept Psychiat, Tobacco Use Res Ctr, Philadelphia, PA 19104 USA. [Lerman, Caryn] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Uhl, GR (reprint author), Natl Inst Drug Abuse, Mol Neurobiol Branch, Natl Inst Hlth, Intramural Res Program, 333 Cassell Dr,Str 3510, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012; OI Liu, Qing-Rong/0000-0001-8477-6452; David, Sean/0000-0002-4922-2603 FU Intramural NIH HHS; NCI NIH HHS [P50 CA084719, P50CA/DA84718, P50CA84719, R01 CA063562, R01CA 63562]; NHLBI NIH HHS [HL32318]; NIDA NIH HHS [K08 DA014276-01A2, 1K08 DA14276-05, DA08511, K08 DA014276, K08 DA014276-02, K08 DA014276-03, K08 DA014276-04, K08 DA014276-05] NR 59 TC 151 Z9 154 U1 2 U2 9 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 JUN PY 2008 VL 65 IS 6 BP 683 EP 693 DI 10.1001/archpsyc.65.6.683 PG 11 WC Psychiatry SC Psychiatry GA 308PX UT WOS:000256403600009 PM 18519826 ER PT J AU Gutti, U Fung, HC Hruska, KS LaMarca, ME Chen, CM Wu, YR Sidransky, E AF Gutti, Usha Fung, Hon-Chung Hruska, Kathleen S. LaMarca, Mary E. Chen, Chiung-Mei Wu, Yih-Ru Sidransky, Ellen TI The need for appropriate genotyping strategies for glucocerebrosidase mutations in cohorts with Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Letter ID EARLY-ONSET; TAIWAN; RISK; GENE C1 [Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov OI Gutti, Usha/0000-0003-0927-0923 FU Intramural NIH HHS [Z01 HG200336-02] NR 6 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2008 VL 65 IS 6 BP 850 EP 851 DI 10.1001/archneur.65.6.850 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 310RZ UT WOS:000256549100031 PM 18541817 ER PT J AU Rovner, AJ O'Brien, KO AF Rovner, Alisha J. O'Brien, Kimberly O. TI Hypovitaminosis D among healthy children in the United States - A review of the current evidence SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Review ID VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D CONCENTRATIONS; BREAST-FED INFANTS; NUTRITIONAL RICKETS; D INSUFFICIENCY; FORTIFIED MILK; PARATHYROID-HORMONE; D FORTIFICATION; ADOLESCENTS; RISK AB Objective: To review the published literature on serum 25-hydroxyvitamin D concentrations in US children. Data Sources: Articles were. identified by searching MEDLINE using 25-hydroxyvitamin D, vitamin D, hypovitaminosis D, vitamin D insufficiency, vitamin D deficiency, children, and adolescents as key words and by screening references from original studies. Study Selection: Studies were included if they fulfilled the following a priori criteria: contained a well-defined sample of children, included only healthy children, presented data on serum 25-hydroxyvitamin D concentrations, were published in the past 10 years, and were conducted in the United States. Data Extraction: Serum 25-hydroxyvitamin D concentrations and prevalence of low vitamin D status (hypovitaminosis D). Data Synthesis: Fourteen articles fulfilled the criteria. There were no consistent definitions of hypovitaminosis D; values corresponding to vitamin D deficiency ranged from less than 5 ng/mL to less than 12 ng/mL, and those for vitamin D insufficiency ranged from less than 10 ng/mL to less than 32 ng/mL (to convert 25-hydroxyvitamin D concentrations to nanomoles per liter, multiply by 2.496). The following assays were used: radioinummoassay (7 studies), competitive binding protein assay (3 studies), automated chemiluminescence protein-binding assay (3 studies), and enzyme-linked immunosorbent assay (1 study). Breastfed infants in winter who did not receive vitamin D supplementation were the most severely vitamin D deficient (78%). Estimates of the prevalence of hypovitaminosis D ranged, from 1% to 78%. Older age, winter season, higher body mass index, black race/ethnicity, and elevated parathyroid hormone concentrations were associated with lower 25-hydroxyvitamin D concentrations. Conclusion: Although overt vitamin D deficiency is no longer common in US children, lesser degrees of vitamin D insufficiency are widespread. C1 [Rovner, Alisha J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, Rockville, MD 20852 USA. [O'Brien, Kimberly O.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. RP Rovner, AJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, 610 Execut Blvd,Room 7B13A,MSC 7510, Rockville, MD 20852 USA. EM rovneral@mail.nih.gov NR 51 TC 95 Z9 98 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 2008 VL 162 IS 6 BP 513 EP 519 DI 10.1001/archpedi.162.6.513 PG 7 WC Pediatrics SC Pediatrics GA 311VB UT WOS:000256627400002 PM 18524740 ER PT J AU Chan, L Ciol, MA Shumway-Cook, A Yorkston, KM Dudgeon, BJ Asch, SM Hoffman, JM AF Chan, Leighton Ciol, Marcia A. Shumway-Cook, Anne Yorkston, Kathryn M. Dudgeon, Brian J. Asch, Steven M. Hoffman, Jeanne M. TI A longitudinal evaluation of persons with disabilities: Does a longitudinal definition help define who receives necessary care? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE disability evaluation; medicare; rehabilitation ID MEDICARE BENEFICIARIES; HEALTH-CARE; POPULATION; SERVICES; SATISFACTION; PEOPLE; COSTS AB Objective: To assess, using a longitudinal definition, the impact of disability on a broad range of objective health care quality indicators. Design: Longitudinal cohort study following up with patients over several years. The first 2 interviews, 1 year apart, were used to determine each patient's disability status in activities of daily living (ADLs). Assessment of the health care indicators commenced after the second interview and continued throughout the survey period (an additional 1-3y). Setting: National survey. Participants: Participants (N = 29,074) of the Medicare Current Beneficiary Survey (1992-2001) with no, increasing, decreasing, and stable ADL disability. Interventions: Not applicable. Main Outcome Measure: The incidence of 5 avoidable outcomes, receipt of 3 preventive care measures, and adherence to 32 diagnostically based indicators assessing the quality of treatment for acute myocardial infarction [AMI], angina, breast cancer, cerebrovascular accident, transient ischemic attack, cholelithiasis, chronic obstructive pulmonary disease [COPD], congestive heart failure, depression, gastrointestinal bleeding, diabetes, and hypertension. Results: For most indicators, less than 75% of eligible patients received necessary care, regardless of disability status. For 5 indicators, less than 50% of patients received appropriate treatment. In a logistic regression analysis that controlled for patient age, sex, race, and income, disability status was a significant factor in 7 quality measures (AMI, breast cancer, COPD, diabetes, angina, pneumonia, annual visits). Conclusions: Using a longitudinal definition of disability and objective health quality indicators, we found that disability status can be an important factor in determining receipt of quality health care in a broad range of diagnostic categories. However, the impact of disability status varies depending on the indicator measured. In this cohort of patients, the changing nature of a person's disability seems to have less impact than whether they ever have had any functional deficits. C1 [Chan, Leighton] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. [Ciol, Marcia A.; Shumway-Cook, Anne; Yorkston, Kathryn M.; Dudgeon, Brian J.; Asch, Steven M.] Univ Washington, Sch Med, Seattle, WA USA. [Hoffman, Jeanne M.] W Los Angeles Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Los Angeles, CA 90073 USA. RP Chan, L (reprint author), NIH, Dept Rehabil Med, Clin Res Ctr, Bldg 10,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM chanle@cc.nih.gov FU Intramural NIH HHS [ZIA CL060072-04]; PHS HHS [MM-0625-04/04] NR 20 TC 16 Z9 16 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2008 VL 89 IS 6 BP 1023 EP 1030 DI 10.1016/j.apmr.2007.10.045 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 310TN UT WOS:000256553400003 PM 18503795 ER PT J AU Chan, PC Sills, RC Kissling, GE Nyska, A Richter, W AF Chan, P. C. Sills, R. C. Kissling, G. E. Nyska, A. Richter, W. TI Induction of thyroid and liver tumors by chronic exposure to 2-methylimidazole in F344/N rats and B6C3F1 mice SO ARCHIVES OF TOXICOLOGY LA English DT Article DE 2-methylimidazole; thyroid; liver; tumors; granuloma; rats; mice ID ZERO-DOSE CONTROL; RETENTION MECHANISM; CONNECTIVE-TISSUE; GLAND NEOPLASIA; LONG-TERM; IMIDAZOLES; IDENTIFICATION; CATTLE; MILK AB 2-Methylimidazole (2MI) has been identified as a by-product of fermentation and is detected in foods and mainstream and side-stream tobacco smoke. It is used in the manufacture of pharmaceuticals, photographic chemicals, dyes and pigments, agricultural chemicals, and rubber. Carcinogenicity studies of 2MI were conducted because of its high potential for human exposure and a lack of carcinogenicity data. Groups of male and female Fischer 344/N rats were fed diets containing 0, 300, 1,000, or 3,000 ppm (males) or 0, 1,000, 2,500, or 5,000 ppm (females) 2MI for 106 weeks and groups of male and female B6C3F1 mice were fed 0, 625, 1,250, or 2,500 ppm 2MI for 105 weeks. Animals in each group were sacrificed at 8 days, 14 weeks, and 6 months for determinations of serum thyroid hormone and liver enzyme levels and histopathological examinations and at 2 years for evaluations of neoplastic lesions. In rats, 2MI administration reduced serum thyroxine and triiodothyronine and increased thyroid stimulating hormone levels. 2MI administration also increased total hepatic UDP-glucuronosyltransferase levels. At 2 years, the incidences of thyroid follicular cell hyperplasia, adenoma or carcinoma (combined), as well as follicular mineralization were increased. The incidences of hepatocellular adenoma or carcinoma (combined) in the two highest dose groups of males and females were also increased. The incidences of mixed cell focus in males and females were also significantly increased. In mice, the incidences of thyroid follicular cell hypertrophy and hyperplasia were significantly increased in the high dose males and females. The incidence of thyroid follicular cell adenoma in the 2,500 ppm males was significantly greater than that in the control group. The incidences of hepatocellular adenoma or carcinoma (combined) were significantly increased in all exposed groups of males and in the 2,500 ppm females. Significant increases in incidences were also observed in spleen hematopoietic cell proliferation in both sexes and bone marrow hyperplasia, chronic active inflammation of the epididymis, sperm granuloma, and germinal epithelial atrophy of the testis in males. Under these experimental conditions, carcinogenic activity of 2MI was demonstrated in male and female rats and mice. C1 [Chan, P. C.; Sills, R. C.; Kissling, G. E.; Nyska, A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Richter, W.] So Res Inst, Birmingham, AL 35255 USA. RP Chan, PC (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov NR 41 TC 16 Z9 17 U1 1 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JUN PY 2008 VL 82 IS 6 BP 399 EP 412 DI 10.1007/s00204-007-0249-7 PG 14 WC Toxicology SC Toxicology GA 306MH UT WOS:000256252000008 PM 17924096 ER PT J AU Amar, MJ Pryor, M Demosky, S Stonik, J Remaley, AT AF Amar, Marcelo J. Pryor, Milton Demosky, Steve Stonik, John Remaley, Alan T. TI Mechanism for hypertriglyceridemia caused by treatment with apoA-I or the 5a apoA-I mimetic peptide SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Amar, Marcelo J.; Pryor, Milton; Demosky, Steve; Stonik, John; Remaley, Alan T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P136 BP E58 EP E59 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400160 ER PT J AU Buono, C Amar, M Kruth, H AF Buono, Chiara Amar, Marcelo Kruth, Howard TI Fluid-phase pinocytosis mediates macrophage uptake of LDL-sized nanoparticles in mouse atherosclerotic lesions SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Buono, Chiara; Amar, Marcelo; Kruth, Howard] NHLBI, NIH, Bethesda, MD 20892 USA. [Buono, Chiara] VisEn Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P141 BP E59 EP E59 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400165 ER PT J AU Gupta, R Ma, MC Fang, F Mellad, JA Beltran, LE Ding, SL Kovacic, JC Boehm, M AF Gupta, Rohit Ma, Mingchao Fang, Fang Mellad, Jason A. Beltran, Leilani E. Ding, Shunli Kovacic, Jason C. Boehm, Manfred TI p21(cip1) inhibits NF-kappa B mediated transcriptional activation of RANTES expression in vascular smooth muscle cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Gupta, Rohit] NHLBI, NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P628 BP E148 EP E148 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400616 ER PT J AU Hossaine, MA Akita, N Tsujita, M Gonzalez, FJ Remaley, AT Yokoyama, S AF Hossaine, M. Anwar Akita, Nobukatsu Tsujita, Maki Gonzalez, Frank J. Remaley, Alan T. Yokoyama, Shinji TI Cholesterol homeostasis in LCAT, ABCA1, ABCG1, PPAR alpha, and SRB1-deficient mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Hossaine, M. Anwar; Akita, Nobukatsu; Tsujita, Maki; Yokoyama, Shinji] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi, Japan. [Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. [Remaley, Alan T.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P481 BP E120 EP E120 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400479 ER PT J AU O'Brien, K Walts, AD Stonik, JA Demosky, SJ Malide, D Combs, CA Remaley, AT Neufeld, EB AF O'Brien, Katherine Walts, Avram D. Stonik, John A. Demosky, Stephen J. Malide, Daniela Combs, Christian A. Remaley, Alan T. Neufeld, Edward B. TI ABCG1 mobilizes plasma membrane and endosomal nonsphingomyelin-associated cholesterol for efflux SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [O'Brien, Katherine; Walts, Avram D.; Stonik, John A.; Demosky, Stephen J.; Malide, Daniela; Combs, Christian A.; Remaley, Alan T.; Neufeld, Edward B.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA 4 BP E32 EP E32 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400032 ER PT J AU Perry, TE Song, MJ Despres, DJ Kim, SM San, H Yu, ZX Raghavachari, N Schnermann, J Cannon, RO Orlic, D AF Perry, Tashera E. Song, Minjung Despres, Daryl J. Kim, Soo Mi San, Hong Yu, Zu-Xi Raghavachari, Nalini Schnermann, Jurgen Cannon, Richard O. Orlic, Donald TI Bone marrow-derived cells do not replace endothelium in a murine model of chronic endothelial cell dysfunction SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Perry, Tashera E.; Song, Minjung; Yu, Zu-Xi; Raghavachari, Nalini; Cannon, Richard O.; Orlic, Donald] NHLBI, NIH, Bethesda, MD 20892 USA. [Despres, Daryl J.] NINDS, NIH, Bethesda, MD 20892 USA. [Kim, Soo Mi; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA. [San, Hong] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA 70 BP E45 EP E45 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400097 ER PT J AU Rutherford, S Goring, HH Laston, SL Haack, K Almasy, LA Comuzzle, AG Lee, ET Best, LG Fabsitz, RR Devereux, RB North, KE Franceschini, N Howard, BV MacCluer, JW Cole, SA AF Rutherford, Sue Goering, Harald H. Laston, Sandy L. Haack, Karin Almasy, Laura A. Comuzzle, Anthony G. Lee, Elisa T. Best, Lyle G. Fabsitz, Richard R. Devereux, Richard B. North, Kari E. Franceschini, Nora Howard, Barbara V. MacCluer, Jean W. Cole, Shelley A. TI A diastolic blood pressure quantitative trait locus on chromosome 10 may confer risk of atherosclerosis in the strong heart family study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Rutherford, Sue; Goering, Harald H.; Laston, Sandy L.; Haack, Karin; Almasy, Laura A.; Comuzzle, Anthony G.; MacCluer, Jean W.; Cole, Shelley A.] SW Fdn BioMed Rsch, San Antonio, TX USA. [Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Best, Lyle G.] Missouri Breaks Ind Rsch Inc, Timber Lake, SD USA. [Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA. [Devereux, Richard B.] Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY 10021 USA. [North, Kari E.; Franceschini, Nora] Univ N Carolina, Chapel Hill, NC USA. [Howard, Barbara V.] MedStar Rsch Inst, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P480 BP E120 EP E120 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400478 ER PT J AU Sviridov, D Murphy, A Woolard, K Hoang, A Mukhamedova, N Stizaker, R McCormick, S Remaley, A Chin-Dusting, J AF Sviridov, Dmitri Murphy, Andrew Woolard, Kevin Hoang, Anh Mukhamedova, Nigora Stizaker, Roslynn McCormick, Sally Remaley, Alan Chin-Dusting, Jaye TI High-density lipoprotein reduces the human monocyte inflammatory response through ATP-binding cassette transporter A1 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Sviridov, Dmitri; Murphy, Andrew; Woolard, Kevin; Hoang, Anh; Mukhamedova, Nigora; Chin-Dusting, Jaye] Baker Heart Res Inst, Melbourne, Vic, Australia. [Stizaker, Roslynn] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. [McCormick, Sally] Univ Otago, Dunedin, New Zealand. [Remaley, Alan] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 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 JUN PY 2008 VL 28 IS 6 MA P128 BP E57 EP E57 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400152 ER PT J AU Voogt, JN Turner, SM Chang, B Fessler, C Killion, S Amar, MJ Remaley, AT AF Voogt, Jason N. Turner, Scott M. Chang, Betty Fessler, Chancy Killion, Salena Amar, Marcelo J. Remaley, Alan T. TI Effect of the 5A bi-helical ApoA-I mimetic peptide on cholesterol efflux and global reverse cholesterol transport in vivo SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Amar, Marcelo J.; Remaley, Alan T.] NIH, Bethesda, MD 20892 USA. [Voogt, Jason N.; Turner, Scott M.; Chang, Betty; Fessler, Chancy; Killion, Salena] KineMed Inc, Emeryville, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P170 BP E65 EP E65 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400194 ER PT J AU Jacobi, AM Reiter, K Mackay, M Aranow, C Hiepe, F Radbruch, A Hansen, A Burmester, GR Diamond, B Lipsky, PE Dorner, T AF Jacobi, Annett M. Reiter, Karin Mackay, Meggan Aranow, Cynthia Hiepe, Falk Radbruch, Andreas Hansen, Arne Burmester, Gerd-R. Diamond, Betty Lipsky, Peter E. Doerner, Thomas TI Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus - Delineation by expression of CD27, IgD, and CD95 SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PERIPHERAL-BLOOD; LYMPHOCYTES; FAS; POPULATION; IDENTIFICATION; APOPTOSIS; GENES; IMMUNOGLOBULIN; PROTECTION; FREQUENCY AB Objective. Analysis of peripheral B cell subsets in patients with systemic lupus erythematosus (SLE) has provided evidence of specific alterations, such as an expansion of CD27++ plasma cells/blasts and transitional B cells. However, memory B cells in lupus have not been thoroughly investigated, and only recently a CD27- memory B cell subset was identified in the peripheral blood of lupus patients. Focusing on CD27-B cells, this study aimed to identify abnormalities in peripheral B cell subsets in patients with SLE., Methods. Three independent cohorts of lupus patients were used to characterize CD27- memory B cells, using multiparameter flow cytometry and single-cell reverse transcription-polymerase chain reaction of heavy-chain transcripts. Results. We identified a homogeneous subset of CD27-,IgD-,CD95+ memory B cells with an activated phenotype that was increased in patients with disease flares and that correlated with disease activity and serologic abnormalities. In contrast, the entire subset of CD27--,IgD- B cells was found to be heterogeneous, did not correlate significantly with lupus activity, and was also increased in patients with bacterial infections. Conclusion. We conclude that CD95 is a useful marker to identify CD27- memory B cells with an activated phenotype, which might serve as a biomarker for lupus activity and as a target of further investigations aiming to elucidate the pathogenic potential of these cells and the mechanisms involved in the generation as well as regulation of this CD27-,IgD-,CD95+ memory B cell subset. C1 [Jacobi, Annett M.; Reiter, Karin; Hiepe, Falk; Hansen, Arne; Doerner, Thomas] Charite Univ Med Berlin, D-10098 Berlin, Germany. [Jacobi, Annett M.; Mackay, Meggan; Aranow, Cynthia; Diamond, Betty] Feinstein Inst Med Res, Manhasset, NY USA. [Hiepe, Falk; Radbruch, Andreas; Doerner, Thomas] Deutsch Rheumaforschungszentrum, Berlin, Germany. [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Charite Univ Med Berlin, Charitepl 1, D-10098 Berlin, Germany. EM Thomas.doerner@charite.de RI Hiepe, Falk/A-9416-2013 NR 35 TC 99 Z9 106 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2008 VL 58 IS 6 BP 1762 EP 1773 DI 10.1002/art.23498 PG 12 WC Rheumatology SC Rheumatology GA 313EW UT WOS:000256724900024 PM 18512812 ER PT J AU Tao, X Fan, F Hoffmann, V Gao, CY Longo, NS Zerfas, P Lipsky, PE AF Tao, Xuelian Fan, Fred Hoffmann, Victoria Gao, Chun Y. Longo, Nancy S. Zerfas, Patricia Lipsky, Peter E. TI Effective therapy for nephritis in (NZB x NZW)F(1) mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; ETHYL-ACETATE EXTRACT; SYSTEMIC-LUPUS-ERYTHEMATOSUS; FACTOR-KAPPA-B; GENE-TRANSCRIPTION; RENAL-DISEASE; NITRIC-OXIDE; PLASMA-CELLS; NZB/W MICE; INHIBITION AB Objective. Triptolide and tripdiolide are thought to be active components of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown to be effective in treating murine lupus nephritis. This study was undertaken to examine the therapeutic effect of triptolide and tripdiolide on established lupus nephritis in (NZB X NZW)F(1) mice. Methods. (NZB x NZW)F(1) mice were treated with vehicle, triptolide, or tripdiolide for 15 weeks beginning at the age of 29 weeks (after the development of lupus nephritis). Body weight, proteinuria, and anti-double-stranded DNA (anti-dsDNA) antibodies were monitored, and the kidney and spleen were assessed histologically. Culture supernatants of spleen mononuclear cells were assayed for cytokines. Results. By 28 weeks, most (NZB X NZW)F(1) mice had developed lupus nephritis. Vehicle-treated mice exhibited progressive proteinuria, hypoalbuminemia, elevated blood urea nitrogen (BUN) levels, and evidence of severe nephritis. In contrast, proteinuria and BUN levels were significantly reduced in mice treated with either triptolide or tripdiolide as compared with those treated with vehicle. There was no hypoalbuminemia or apparent evidence of lupus nephritis in mice treated with either of the 2 diterpenoids. At 44 weeks of age, the survival rate in mice treated with vehicle (35.7%) was markedly lower than that in mice treated with either triptolide (87.5%) or tripdiolide (88.2%). The mean level of anti-dsDNA antibody in mice treated with tripdiolide was lower than that in the vehicle-treated mice upon completion of the treatment course. Production of tumor necrosis factor, interleukin-6, and monocyte chemoattractant protein 1 by spleen cells was also decreased after diterpenoid therapy. Conclusion. Therapy with triptolide or tripdiolide significantly ameliorated lupus nephritis in (NZB X NZW)F(1) mice, reduced cytokine and chemokine production, and prolonged survival. C1 [Tao, Xuelian; Fan, Fred; Longo, Nancy S.; Lipsky, Peter E.] NIAMSD, Natl Inst Hlth, Autoimmun Branch, Bethesda, MD 20892 USA. [Hoffmann, Victoria; Zerfas, Patricia] Off Res Serv, Div Vet Resources, NIH, Bethesda, MD USA. [Gao, Chun Y.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Natl Inst Hlth, Autoimmun Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [P01 AI031229-09, R01 AI039230-04, R13 AI045697-01]; NIAMS NIH HHS [T32 AR007055-25] NR 34 TC 16 Z9 21 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2008 VL 58 IS 6 BP 1774 EP 1783 DI 10.1002/art.23513 PG 10 WC Rheumatology SC Rheumatology GA 313EW UT WOS:000256724900025 PM 18512813 ER PT J AU Petri, M Kasitanon, N Lee, SS Link, K Magder, L Bae, SC Hanly, JG Isenberg, DA Nived, O Sturfelt, G van Vollenhoven, R Wallace, DJ Alarcon, GS Adu, D Avila-Casado, C Bernatsky, SR Bruce, IN Clarke, AE Contreras, G Fine, DM Gladman, DD Gordon, C Kalunian, KC Madaio, MP Rovin, BH Sanchez-Guerrero, J Steinsson, K Aranow, C Balow, JE Buyon, JP Ginzler, EM Khamashta, MA Urowitz, MB Dooley, MA Merrill, JT Ramsey-Goldman, R Font, J Tumlin, J Stoll, T Zoma, A AF Petri, Michelle Kasitanon, Nuntana Lee, Shin-Seok Link, Kimberly Magder, Laurence Bae, Sang-Cheol Hanly, John G. Isenberg, David A. Nived, Ola Sturfelt, Gunnar van Vollenhoven, Ronald Wallace, Daniel J. Alarcon, Graciela S. Adu, Dwomoa Avila-Casado, Carmen Bernatsky, Sasha R. Bruce, Ian N. Clarke, Ann E. Contreras, Gabriel Fine, Derek M. Gladman, Dafna D. Gordon, Caroline Kalunian, Kenneth C. Madaio, Michael P. Rovin, Brad H. Sanchez-Guerrero, Jorge Steinsson, Kristjan Aranow, Cynthia Balow, James E. Buyon, Jill P. Ginzler, Ellen M. Khamashta, Munther A. Urowitz, Murray B. Dooley, Mary Anne Merrill, Joan T. Ramsey-Goldman, Rosalind Font, Josef Tumlin, James Stoll, Thomas Zoma, Asad CA Systemic Lupus Int Collaborating C TI Systemic lupus international collaborating clinics renal activity/response exercise - Development of a renal activity score and renal response index SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MYCOPHENOLATE-MOFETIL; ERYTHEMATOSUS; NEPHRITIS; PROTEINURIA; CREATININE; DISEASE AB Objective. To develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index. Methods. Abstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index. Results. The renal activity score was computed as follows: proteinuria 0.5-1 gm/day (3 points), proteinuria >1-3 gm/day (5 points), proteinuria >3 gm/day (11 points), urine red blood cell count > 10/high-power field (3 points), and urine white blood cell count >10/high-power field (I point). The chance-adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59-0.79). Conclusion. Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings. C1 [Petri, Michelle; Kasitanon, Nuntana; Lee, Shin-Seok; Link, Kimberly; Fine, Derek M.] Johns Hopkins Univ, Dept Rheumatol, Baltimore, MD 21205 USA. [Magder, Laurence] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Bae, Sang-Cheol] Hanyang Univ, Med Ctr, Seoul 133791, South Korea. [Bae, Sang-Cheol] Hosp Rheumat Dis, Seoul, South Korea. [Hanly, John G.] Queen Elizabeth II Med Ctr, Halifax, NS, Canada. [Isenberg, David A.] UCL, London, England. [Sturfelt, Gunnar] Univ Lund Hosp, S-22185 Lund, Sweden. [van Vollenhoven, Ronald] Karolinska Univ Hosp, Stockholm, Sweden. [Wallace, Daniel J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Alarcon, Graciela S.] Univ Alabama, Birmingham, AL USA. [Adu, Dwomoa] Queen Elizabeth Hosp, Birmingham, W Midlands, England. [Avila-Casado, Carmen] Inst Nacl Cardiol Ignacio Chavez, Mexico City, DF, Mexico. [Bernatsky, Sasha R.; Clarke, Ann E.] Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. [Bernatsky, Sasha R.; Clarke, Ann E.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Bruce, Ian N.] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England. [Contreras, Gabriel] Univ Miami, Miami, FL USA. [Gladman, Dafna D.; Urowitz, Murray B.] Univ Toronto, Toronto, ON, Canada. [Gladman, Dafna D.; Urowitz, Murray B.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. [Gordon, Caroline] Univ Birmingham, Birmingham, W Midlands, England. [Kalunian, Kenneth C.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Madaio, Michael P.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Rovin, Brad H.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Sanchez-Guerrero, Jorge] Natl Inst Nutr, Mexico City, DF, Mexico. [Steinsson, Kristjan] Landspitali Univ Hosp, Reykjavik, Iceland. [Aranow, Cynthia] Columbia Univ, Med Ctr, New York, NY USA. [Balow, James E.] NIDDK, NIH, Bethesda, MD USA. [Buyon, Jill P.] Hosp Joint Dis & Med Ctr, New York, NY USA. [Ginzler, Ellen M.] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Khamashta, Munther A.] St Thomas Hosp, London, England. [Khamashta, Munther A.] Kings Coll London, London WC2R 2LS, England. [Dooley, Mary Anne] Univ N Carolina, Chapel Hill, NC USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Tumlin, James] Univ N Carolina, Charlotte, NC 28223 USA. [Stoll, Thomas] Kantonsspital, Schatthausen, Switzerland. [Zoma, Asad] Hairmyres Hosp, E Kilbride, Lanark, Scotland. RP Petri, M (reprint author), Johns Hopkins Univ, Dept Rheumatol, 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@jhmi.edu OI Isenberg, David/0000-0001-9514-2455; Bruce, Ian/0000-0003-3047-500X FU NCRR NIH HHS [M01-RR-00052]; NIAMS NIH HHS [AR-43727, K24 AR002138] NR 18 TC 31 Z9 33 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2008 VL 58 IS 6 BP 1784 EP 1788 DI 10.1002/art.23456 PG 5 WC Rheumatology SC Rheumatology GA 313EW UT WOS:000256724900026 PM 18512819 ER PT J AU Petri, M Kasitanon, N Singh, S Link, K Magder, L Bae, SC Hanly, JG Nived, O Sturfelt, G van Vollenhoven, R Wallace, DJ Alarcon, GS Adu, D Avila-Casado, C Bernatsky, SR Bruce, IN Clarke, AE Contreras, G Fine, DM Gladman, DD Gordon, C Kalunian, KC Madaio, MP Rovin, BH Sanchez-Guerrero, J Steinsson, K Aranow, C Balow, JE Buyon, JP Ginzler, EM Khamashta, MA Urowitz, MB Dooley, MA Merrill, JT Ramsey-Goldman, R Font, J Tumlin, J Stoll, T Zoma, A AF Petri, Michelle Kasitanon, Nuntana Singh, Sukminder Link, Kimberly Magder, Laurence Bae, Sang-Cheol Hanly, John G. Nived, Ola Sturfelt, Gunnar van Vollenhoven, Ronald Wallace, Daniel J. Alarcon, Graciela S. Adu, Dwomoa Avila-Casado, Carmen Bernatsky, Sasha R. Bruce, Ian N. Clarke, Ann E. Contreras, Gabriel Fine, Derek M. Gladman, Dafna D. Gordon, Caroline Kalunian, Kenneth C. Madaio, Michael P. Rovin, Brad H. Sanchez-Guerrero, Jorge Steinsson, Kristjan Aranow, Cynthia Balow, James E. Buyon, Jill P. Ginzler, Ellen M. Khamashta, Munther A. Urowitz, Murray B. Dooley, Mary Anne Merrill, Joan T. Ramsey-Goldman, Rosalind Font, Josef Tumlin, James Stoll, Thomas Zoma, Asad CA Systemic Lupus Int Collaborating C TI Systemic lupus international collaborating clinics renal activity/response exercise - Comparison of agreement in rating renal response SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DISEASE-ACTIVITY INDEX; MYCOPHENOLATE-MOFETIL; SERUM CREATININE; ERYTHEMATOSUS; NEPHRITIS; PREDICTION; VALIDATION; REMISSION AB Objective. To assess the degree to which physicians agree with each other and with ratings obtained with 3 existing responder indices, in rating the response to treatment of lupus nephritis. Methods. Lupus nephritis patient medical records from 125 pairs of visits (6 months apart) were used to create renal response scenarios. Seven nephrologists and 22 rheumatologists rated each scenario as demonstrating complete response, partial response, same, or worsening. The plurality (most frequent) rating of renal response by the physicians was compared with the calculated score from the renal component of the British Isles Lupus Assessment Group (BILAG) index (original and updated [2004] version) and of the Responder Index for Lupus Erythematosus (RIFLE). The degree of agreement among the physicians was assessed by calculating intraclass correlation coefficients (ICCs). The degree of agreement between the plurality physician rating and ratings obtained with the established response indices was assessed using the kappa statistic. Results. The ICC among all physicians was 0.64 (0.62 for nephrologists and 0.67 for rheumatologists). The chance-adjusted measure of agreement (kappa coefficient) between the plurality physician rating and the calculated score obtained using established indexes was 0.50 (95% confidence interval [95% CI] 0.38-0.61) for the RIFLE, 0.14 (95% CI 0.03-6.25) for the original BILAG, and 0.23 (95% CI 0.21-0.44) for the BILAG 2004. Conclusion. These findings indicate that rheumatologists as a group and nephrologists as a group have equal agreement in their rating of renal response. There was moderate agreement between plurality physician ratings and ratings obtained using the renal component of the RIFLE. Ratings of response using an index based on the original BILAG did not have good agreement with the plurality physician rating. C1 [Petri, Michelle; Kasitanon, Nuntana; Singh, Sukminder; Link, Kimberly; Fine, Derek M.] Johns Hopkins Univ, Dept Rheumatol, Baltimore, MD 21205 USA. [Magder, Laurence] Univ Maryland, Baltimore, MD 21201 USA. [Bae, Sang-Cheol] Hosp Rheumat Dis, Seoul, South Korea. [Bae, Sang-Cheol] Hanyang Univ, Med Ctr, Seoul 133791, South Korea. [Hanly, John G.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Nived, Ola; Sturfelt, Gunnar] Univ Lund Hosp, S-22185 Lund, Sweden. [van Vollenhoven, Ronald] Karolinska Univ Hosp, Stockholm, Sweden. [Wallace, Daniel J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Alarcon, Graciela S.] Univ Alabama, Birmingham, AL USA. [Adu, Dwomoa] Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England. [Avila-Casado, Carmen] Inst Nacl Cardiol Ignacio Chavez, Mexico City, DF, Mexico. [Bernatsky, Sasha R.; Clarke, Ann E.] Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. [Bernatsky, Sasha R.; Clarke, Ann E.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Bruce, Ian N.] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England. [Contreras, Gabriel] Univ Miami, Miami, FL USA. [Gladman, Dafna D.; Urowitz, Murray B.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. [Gladman, Dafna D.; Urowitz, Murray B.] Univ Toronto, Toronto, ON, Canada. [Gordon, Caroline] Univ Birmingham, Birmingham, W Midlands, England. [Kalunian, Kenneth C.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Madaio, Michael P.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Rovin, Brad H.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Sanchez-Guerrero, Jorge] Natl Inst Nutr, Mexico City, DF, Mexico. [Steinsson, Kristjan] Landspitali Univ HOsp, Reykjavik, Iceland. [Aranow, Cynthia] Columbia Univ, Med Ctr, New York, NY USA. [Balow, James E.] NIDDK, NIH, Bethesda, MD USA. [Buyon, Jill P.] NYU, Hosp Joint Dis, Sch Med, New York, NY 10003 USA. [Ginzler, Ellen M.] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Khamashta, Munther A.] St Thomas Hosp, London, England. [Khamashta, Munther A.] Kings Coll London, London WC2R 2LS, England. [Dooley, Mary Anne] Univ N Carolina, Chapel Hill, NC USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Tumlin, James] Univ N Carolina, Charlotte, NC 28223 USA. [Stoll, Thomas] Kantonsspital, Schatthausen, Switzerland. [Zoma, Asad] Hairmyres Hosp, E Kilbride, Lanark, Scotland. RP Petri, M (reprint author), Johns Hopkins Univ, Dept Rheumatol, 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@jhmi.edu OI Bruce, Ian/0000-0003-3047-500X FU NCRR NIH HHS [M01-RR-00052]; NIAMS NIH HHS [AR-43727, K24 AR002138] NR 18 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2008 VL 58 IS 6 BP 1789 EP 1795 DI 10.1002/art.23802 PG 7 WC Rheumatology SC Rheumatology GA 313EW UT WOS:000256724900027 PM 18512814 ER PT J AU Chang, M Saiki, RK Cantanese, JJ Lew, D van der Helm-van Mil, AHM Toes, REM Huizinga, TWJ Ardlie, KG Criswell, LA Seldin, MF Amos, CI Kastner, DL Gregersen, PK Schrodi, SJ Begovich, AB AF Chang, Monica Saiki, Randall K. Cantanese, Joseph J. Lew, David van der Helm-van Mil, Annette H. M. Toes, Rene E. M. Huizinga, Thomas W. J. Ardlie, Kristin G. Criswell, Lindsey A. Seldin, Michael F. Amos, Christopher I. Kastner, Daniel L. Gregersen, Peter K. Schrodi, Steven J. Begovich, Ann B. TI The inflammatory disease-associated variants in IL12B and IL23R are not associated with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; SEQUENCE VARIANTS; GENE; MULTIPLE; RISK; PSORIASIS C1 [Chang, Monica; Saiki, Randall K.; Cantanese, Joseph J.; Lew, David; Schrodi, Steven J.; Begovich, Ann B.] Celera, Alameda, CA USA. [van der Helm-van Mil, Annette H. M.; Toes, Rene E. M.; Huizinga, Thomas W. J.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Ardlie, Kristin G.] MIT, Board Inst, Cambridge, MA 02139 USA. [Ardlie, Kristin G.] Harvard Univ, Cambridge, MA 02138 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Seldin, Michael F.] Univ Calif Davis, Davis, CA 95616 USA. [Amos, Christopher I.] Univ Texas Houston, Houston, TX USA. [Kastner, Daniel L.] NIAMSD, Bethesda, MD 20892 USA. [Gregersen, Peter K.] Feinstein Inst Med Res N Shore Long Isl Jewish Hl, Manhasset, NY USA. RP Chang, M (reprint author), Celera, Alameda, CA USA. OI Schrodi, Steven/0000-0003-2304-8528 FU Intramural NIH HHS [ZIA AR041139-07] NR 23 TC 28 Z9 29 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2008 VL 58 IS 6 BP 1877 EP 1881 DI 10.1002/art.23492 PG 5 WC Rheumatology SC Rheumatology GA 313EW UT WOS:000256724900037 PM 18512797 ER PT J AU Demers, L Fuhrer, MJ Jutai, JW Scherer, MJ Pervieux, I DeRuyter, F AF Demers, Louise Fuhrer, Marcus J. Jutai, Jeffrey W. Scherer, Marcia J. Pervieux, Isabelle DeRuyter, Frank TI Tracking mobility-related assistive technology in an outcomes study SO ASSISTIVE TECHNOLOGY LA English DT Article DE Assistive technology; follow-up studies; outcomes; mobility; device utilization ID OLDER-ADULTS; DEVICE USE; REHABILITATION; PEOPLE; EQUIPMENT; CARE AB The objective of this follow-up study was to describe changes in the mobility-related assistive technology devices (ATDs) that are used from shortly after discharge from a hospital setting until 5-6 months later. One hundred and thirty-nine participants who had one or more mobility ATDs (canes, crutches, walkers, and wheelchairs) that had been recommended during hospitalization were interviewed an average of 5.5 weeks after discharge and an average of 23.2 weeks later. Information about mobility ATD usage was obtained by questionnaire during face-to-face interviews. The SF-36 was used to assess perceived health status, both physical and mental, as an additional outcome. Results show that at follow-up, only 23.3% of participants were using the ATD provided at baseline as their primary aid. Seven distinct groups of participants were noted based on individual experience with ATD use from the time of discharge to follow-up. Those groups varied according to continued versus discontinued use of an ATD, single versus multiple ATD use across time, and primary versus secondary importance attributed to the ATD. The groups also differed in terms of their differential association with rehabilitation diagnosis, age, as well as physical and mental perceived health status. The findings have implications for designing ATD outcome studies and for interpreting the relationship of ATD outcomes to other variables. The information about changes in mobility-related ATDs can also help rehabilitation specialists at the point of device referral target their patients for interventions that will either increase their adherence to device prescriptions or support nondevice strategies for managing disabilities. C1 [Pervieux, Isabelle] Inst Univ Geriatrie Montreal, Res Ctr, Montreal, PQ H3W 1W5, Canada. [Demers, Louise] Univ Montreal, Sch Rehabil, Montreal, PQ, Canada. [Fuhrer, Marcus J.] NICHHD, NIH, Columbia, MD USA. [Jutai, Jeffrey W.] Univ Western Ontario, Dept Phys Med & Rehabil, London, ON, Canada. [Scherer, Marcia J.] Inst Matching Person & Technol, Webster, NY USA. [DeRuyter, Frank] Duke Univ, Med Ctr, Div Speech Pathol & Audiol, Durham, NC 27710 USA. RP Demers, L (reprint author), Inst Univ Geriatrie Montreal, Res Ctr, 4565 Queen Mary Rd, Montreal, PQ H3W 1W5, Canada. OI Scherer, Marcia/0000-0001-8374-6526; Jutai, Jeffrey/0000-0002-7294-1323 NR 34 TC 12 Z9 12 U1 1 U2 6 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SUM PY 2008 VL 20 IS 2 BP 73 EP 83 PG 11 WC Rehabilitation SC Rehabilitation GA 318IC UT WOS:000257083800002 PM 18646430 ER PT J AU Chadman, KK Gong, SC Scattoni, ML Boltuck, SE Gandhy, SU Heintz, N Crawley, JN AF Chadman, Kathryn K. Gong, Shiaoching Scattoni, Maria L. Boltuck, Sarah E. Gandhy, Shruti U. Heintz, Nathaniel Crawley, Jacqueline N. TI Minimal Aberrant Behavioral Phenotypes of Neuroligin-3 R451C Knockin Mice SO AUTISM RESEARCH LA English DT Article DE autism; mouse model; neuroligin; behavior phenotyping; social behavior ID AUTISM SPECTRUM DISORDER; SOCIAL APPROACH BEHAVIORS; BTBR-T+TF/J MICE; INBRED STRAINS; GENES NLGN3; MUTATIONS; SYNAPSE; PROTEIN; PROBANDS; REVEALS AB Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NI,3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli. C1 [Chadman, Kathryn K.] NIMH, Lab Behav Neurosci, IRP, NIH, Bethesda, MD 20892 USA. [Gong, Shiaoching; Heintz, Nathaniel] Howard Hughes Med Inst, Mol Biol Lab, Chevy Chase, MD USA. [Gong, Shiaoching; Heintz, Nathaniel] Rockefeller Univ, GENSAT Project, New York, NY 10021 USA. [Scattoni, Maria L.] Ist Super Sanita, Behav Neurosci Sect, I-00161 Rome, Italy. RP Chadman, KK (reprint author), NIMH, Lab Behav Neurosci, IRP, NIH, Bldg 35 Room 1C-909,Mail Stop 3730, Bethesda, MD 20892 USA. EM kathryn.chadman@gmail.com FU National Institute of Mental Health Intramural Research Program, Simons Foundation [ISS-NIH 0F14] FX Grant sponsors: National Institute of Mental Health Intramural Research Program, Simons Foundation, ISS-NIH 0F14 NR 44 TC 134 Z9 137 U1 20 U2 34 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD JUN PY 2008 VL 1 IS 3 BP 147 EP 158 DI 10.1002/aur.22 PG 12 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 497CJ UT WOS:000270031700002 PM 19360662 ER PT J AU Pickens, CL AF Pickens, Charles L. TI A limited role for mediodorsal thalamus in devaluation tasks SO BEHAVIORAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-for-Neuroscience CY OCT 14-18, 2006 CL Atlanta, GA SP Soc Neurosci DE mediodorsal thalamus; devaluation; set-shifting; reward ID ORBITAL PREFRONTAL CORTEX; REINFORCER DEVALUATION; RHESUS-MONKEYS; ORBITOFRONTAL CORTEX; BASOLATERAL AMYGDALA; PRELIMBIC CORTEX; BEHAVIORAL FLEXIBILITY; DORSOMEDIAL STRIATUM; SPONTANEOUS-RECOVERY; NEUROTOXIC LESIONS AB Six experiments were performed to determine the role of mediodorsal thalamus (MD) in the devaluation task, varying the type of contingencies (Pavlovian or operant), the number of reinforcers (one vs. two), and the order of experiments (in naive or experimentally experienced rats). MD-lesioned rats were impaired in devaluation performance when switched between Pavlovian and operant devaluation tasks, but not when switched from one Pavlovian devaluation task to another Pavlovian devaluation task. MD lesions caused no devaluation impairment in a multiple-reinforcer Pavlovian devaluation task. These results suggest that MD lesions impair performance in devaluation tasks as a result of an inability to switch the form of associations made from one type of outcome-encoding association to another. This is in accord with previous literature suggesting that MD is needed for strategy set shifting. The results further suggest that MD is a necessary part of devaluation circuits only in cases in which previous associations need to be suppressed in order for new associations to be learned and control behavior, and otherwise the devaluation circuit does not require MD. C1 Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. RP Pickens, CL (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, Suite 200,251 Bayview Blvd, Baltimore, MD 21224 USA. EM pickensc@mail.nih.gov RI Pickens, Charles/E-8984-2010 FU NIMH NIH HHS [R37 MH053667-14, MH53667, R01 MH053667, R37 MH053667, R01 MH065879, MH65879] NR 55 TC 12 Z9 12 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 2008 VL 122 IS 3 BP 659 EP 676 DI 10.1037/0735-7044.122.1659 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 305XE UT WOS:000256210300018 PM 18513136 ER PT J AU Beaton, EA Schulkin, J Swinson, RP Schmidt, LA Antony, MM Hall, GB AF Beaton, Elliott A. Schulkin, Jay Swinson, Richard P. Schmidt, Louis A. Antony, Martin M. Hall, Geoffrey B. TI Different neural responses to stranger and personally familiar faces in shy and bold adults SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE shyness; boldness; fMRI; approach-withdrawal; antygdala ID GENERALIZED SOCIAL PHOBIA; AMYGDALA RESPONSE; AFFECTIVE STYLE; SHYNESS; SOCIABILITY; EXTROVERSION; INHIBITION; ACTIVATION; ASYMMETRY; DOPAMINE AB The shy-bold continuum is a fundamental behavioral trait conserved across human and nonhuman animals. Individual differences along the shy-bold continuum are presumed to arise from, and are maintained by, differences in the excitability of forebrain limbic areas involved in the evaluation of stimulus saliency. To test this hypothesis, the authors conducted an event-related functional MRI (fMRI) study in which brain scans were acquired on shy and bold adults during the presentation of neutral stranger and personally familiar faces. Shy adults exhibited greater bilateral amygdala activation during the presentation of stranger faces and greater left amygdala activation during personally familiar faces than their bold counterparts. Bold adults exhibited greater bilateral nucleus accumbens activation in response to stranger and personally familiar faces than shy adults. Findings suggest that there are distinct neural substrates underlying and maintaining individual differences along a shy-bold continuum in humans. C1 [Schmidt, Louis A.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada. [Beaton, Elliott A.; Swinson, Richard P.; Hall, Geoffrey B.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Beaton, Elliott A.; Swinson, Richard P.; Antony, Martin M.; Hall, Geoffrey B.] St Josephs Healthcare, Brain Body Inst, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Schulkin, Jay] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. [Schulkin, Jay] Georgetown Univ, Sch Med, Dept Neurosci, Washington, DC USA. [Schulkin, Jay] NIMH, Mol Neuroimaging Sect, Bethesda, MD 20892 USA. RP Schmidt, LA (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada. EM schmidtl@mcmaster.ca; hallg@mcmaster.ca RI Antony, Martin/K-1991-2012; OI Antony, Martin/0000-0002-3508-377X; Beaton, Elliott/0000-0001-7631-4637 NR 29 TC 34 Z9 36 U1 4 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 2008 VL 122 IS 3 BP 704 EP 709 DI 10.1037/0735-704.122.3.704 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 305XE UT WOS:000256210300022 PM 18513140 ER PT J AU Barrett, AJ Le Blanc, K AF Barrett, A. John Le Blanc, Katarina TI Prophylaxis of acute GVHD: manipulate the graft or the environment? SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE selective T-cell depletion; regulatory T cells; natural killer cells; mesenchymal stromal cells; calcineurin inhibitors; graft-versus-leukemia ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SUICIDE GENE-THERAPY; DOSE CYCLOSPORINE-A; REGULATORY T-CELLS; SELECTIVE DEPLETION; IMMUNE RECONSTITUTION; DONOR LYMPHOCYTES; UNRELATED DONOR AB Graft-versus-host disease (GVHD) is the immune response of donor T lymphocytes responding to the recipient's alloantigens. The cellular and cytokine mechanisms driving GVHD are now well defined and have led to several prophylactic approaches. Selective allodepletion techniques promise to prevent GVHD without causing immune deficiency provoked by global T-cell depletion. Targeted dosing of other (non-T-cells) cells in the graft - such as CD34(+) progenitors, regulatory T cells, natural killer cells and mesenchymal stromal cells - can also lead to transplants designed to retain immune capability without causing GVHD. Immunosuppressive drugs such as methotrexate, cyclosporine and anti-lymphocyte antibodies are the mainstay in the prevention of GVHD and can be used in conjunction with engineered grafts to eliminate GVHD. In future it is anticipated that further refinements in targeting the elimination or suppression of the GVHD reacting T cells should be selective enough to preserve the important graft-versus-leukemia effect which contributes to the cure of malignant diseases by allogeneic stem-cell transplantation. C1 [Le Blanc, Katarina] Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Clin Immunol & Transfus Med, SE-14186 Stockholm, Sweden. [Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Le Blanc, K (reprint author), Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Clin Immunol & Transfus Med, F79, SE-14186 Stockholm, Sweden. EM katarina.leblanc@ki.se FU Intramural NIH HHS [ZIA HL006105-01] NR 49 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD JUN PY 2008 VL 21 IS 2 BP 165 EP 176 DI 10.1016/j.beha.2008.02.004 PG 12 WC Hematology SC Hematology GA 317FN UT WOS:000257005500007 PM 18503984 ER PT J AU Li, LY Hailey, DW Soetandyo, N Li, W Lippincott-Schwartz, J Shu, HB Ye, YH AF Li, Lianyun Hailey, Dale W. Soetandyo, Nia Li, Wei Lippincott-Schwartz, Jennifer Shu, Hong-bing Ye, Yihong TI Localization of A20 to a lysosome-associated compartment and its role in NF kappa B signaling SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE A20; lysosomal degradation; ubiquitin; NF kappa B; deubiquitinating enzyme ID ZINC-FINGER PROTEIN; NECROSIS-FACTOR RECEPTOR; CELL-DEATH; TNF RECEPTOR-1; ACTIVATION; INHIBITOR; PATHWAYS; SURVIVAL; DOMAIN; TRADD AB A20 is a tumor necrosis factor (TNF)-inducible zinc finger protein that contains both ubiquitinating and deubiquitinating activities. A20 negatively regulates NF kappa B (nuclear factor kappa B) signaling induced by TNF receptor family and Toll-like receptors, but the mechanism of A20 action is poorly defined. Here we show that a fraction of endogenous and ectopically expressed A20 is localized to an endocytic membrane compartment that is in association with the lysosome. The lysosomal association of A20 requires its carboxy terminal zinc finger domains, but is independent of its ubiquitin-modifying activities. Interestingly, A20 mutants defective in membrane association also contain reduced NF kappa B inhibitory activity. These findings suggest the involvement of a lysosome-associated mechanism in A20-dependent termination of NF kappa B signaling. Published by Elsevier B.V. C1 [Li, Lianyun; Soetandyo, Nia; Li, Wei; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Hailey, Dale W.; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. [Shu, Hong-bing] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China. RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 433,5 Ctr Dr, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov FU Intramural NIH HHS [Z01 DK036135-01] NR 39 TC 28 Z9 29 U1 0 U2 7 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 JUN PY 2008 VL 1783 IS 6 BP 1140 EP 1149 DI 10.1016/j.bbamcr.2008.01.029 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312FX UT WOS:000256655600020 PM 18329387 ER PT J AU Kambe, A Iguchi, G Moon, Y Kamitani, H Watanabe, T Eling, TE AF Kambe, Atsushi Iguchi, Genzo Moon, Yuseok Kamitani, Hideki Watanabe, Takashi Eling, Thomas E. TI Regulation of EP4 expression via the Sp-1 transcription factor: Inhibition of expression by anti-cancer agents SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Sp-1 phosphorylation; PPAR; prostaglandin EP4 receptor; glioblastoma; Erks activation ID ACTIVATED PROTEIN-KINASE; HUMAN PANCREATIC-CANCER; CARCINOMA-CELL-GROWTH; PROSTAGLANDIN E-2; CYCLOOXYGENASE-2 EXPRESSION; GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE; PROSTANOID RECEPTORS; SP1 PHOSPHORYLATION; COLORECTAL-CANCER AB For glioblastomas, COX-2 expression is linked to poor survival. COX-2 effects are mediated by the receptors EP2 and EP4, whose regulation is poorly understood. The expression of EP4, and activation or inhibition of EP4 activity in human glioblastoma T98G cells, was found to correlate with growth on soft agar. Chemoprevention drugs, troglitazone (TGZ) and some COX inhibitors, significantly suppressed EP4 expression in T98G cells in a dose dependant manner. Specificity protein 1 (Sp-1) binding sites, located within region -197 to -160 of the human EP4 promoter, are important for the transcription initiation of the human EP4 gene and are responsible for the EP4 suppression by TGZ. Mutation in the Sp-1 sites altered the promoter activity of luciferase constructs and TGZ effects on the promoter. The inhibitory effect of TGZ on EP4 expression was reversed by PD98059, a MEK-1/Erk inhibitor. Immunoprecipitation-Western blot analysis detected Sp-1 phosphorylation that was dependent on TGZ-induced Erks activation. ChIP assay confirmed that Sp-1 phosphorylation decreases its binding to DNA and as a result, leads to the suppression of EP4 expression. Thus, we propose that the expression of EP4 is regulated by Sp-1, but phosphorylation of Sp-1 induced by TGZ suppresses this expression. This represents a new and unique mechanism for the regulation of the EP4 receptor expression. Published by Elsevier B.V. C1 [Kambe, Atsushi; Iguchi, Genzo; Eling, Thomas E.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kambe, Atsushi; Kamitani, Hideki; Watanabe, Takashi] Tottori Univ, Fac Med, Inst Neurol Sci, Div Neurosurg, Tottori 6838504, Japan. [Moon, Yuseok] Pusan Natl Univ, Sch Med, Dept Microbiol & Immunol, Pusan 602739, South Korea. RP Eling, TE (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Eling@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050144-13, Z01 ES010016-09] NR 41 TC 19 Z9 19 U1 0 U2 2 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 JUN PY 2008 VL 1783 IS 6 BP 1211 EP 1219 DI 10.1016/j.bbamcr.2008.01.032 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312FX UT WOS:000256655600026 PM 18346464 ER PT J AU Roy, SW Irimia, M AF Roy, Scott William Irimia, Manuel TI When good transcripts go bad: artifactual RT-PCR 'splicing' and genome analysis SO BIOESSAYS LA English DT Article ID CHORDATE OIKOPLEURA-DIOICA; INTRON LOSS; MESSENGER-RNA; REVERSE TRANSCRIPTION; GAIN; GENES; EVOLUTION; POSITIONS; PLANTS; CONSERVATION AB Gene and intron prediction are essential for accurate inferences about genome evolution. Recently, two genome-wide studies searched for recent intron gains in humans, reaching very different conclusions: either of a complete absence of intron gain since early mammalian evolution, or of creation of numerous introns by genomic duplication in repetitive regions. We discuss one possible explanation: the underappreciated phenomenon of "template switching", by which reverse transcriptase may create artifactual splicing-like events in the preparation of cDNA/EST libraries, may cause complications in searches for newly gained introns in repetitive regions. We report large numbers of apparent template switching in transcript sequences from the intron-poor protists Trichomonas vaginalis and Giardia lamblia. Supplementary material for this article can be found on the BioEssays website (http://www.mrw.interscience. wiley.com/jpages/0265-9247/suppmat/index.htmi). C1 [Roy, Scott William] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. [Irimia, Manuel] Univ Barcelona, Fac Biol, Dept Genet, E-08007 Barcelona, Spain. RP Roy, SW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bldg 38A, Bethesda, MD 20894 USA. EM scottwroy@gmail.com RI Irimia, Manuel/E-3040-2010; OI Irimia, Manuel/0000-0002-2179-2567 FU Intramural NIH HHS NR 29 TC 38 Z9 40 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUN PY 2008 VL 30 IS 6 BP 601 EP 605 DI 10.1002/bies.20749 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 311OE UT WOS:000256608700010 PM 18478540 ER PT J AU Chudasama, Y Wright, KS Murray, EA AF Chudasama, Yogita Wright, Katherine S. Murray, Elisabeth A. TI Hippocampal lesions in rhesus monkeys disrupt emotional responses but not reinforcer devaluation effects SO BIOLOGICAL PSYCHIATRY LA English DT Article DE devaluation; emotion; fear; hippocampus; monkey; perirhinal cortex; reward; snake ID FEAR-POTENTIATED STARTLE; NEUROTOXIC LESIONS; VENTRAL HIPPOCAMPUS; PERIRHINAL CORTEX; MACAQUE MONKEYS; CONTEXTUAL FEAR; PARAHIPPOCAMPAL CORTICES; TEMPORARY INACTIVATION; SELECTIVE LESIONS; AMYGDALA AB Background: Although the role of the hippocampus in emotional behavior has long been recognized, the extent to which the hippocampus plays a role in the regulation and expression of emotion in rhesus monkeys has not been systematically explored. Methods: Rhesus monkeys (Macaca mulatta) with excitotoxic lesions of the hippocampal formation and unoperated control animals were assessed on two different types of emotional processing: defensive reactions to a potential predator (experiment 1) and ability to update the value of positive reinforcers, in this case food (experiment 2). Monkeys with aspiration lesions of the perirhinal cortex were also included in this study as an operated control group. Results: In experiment 1, whereas both operated groups showed reduced latencies to retrieve food located near an innately fear-provoking stimulus, a fake snake, only monkeys with hippocampal lesions displayed reduced defensive reactions to the snake. In experiment 2, both operated groups performed as well as control animals when choosing objects flexibly based on the current value of a food. Conclusions: These findings dissociate the hippocampus and perirhinal cortex in fear expression and specifically implicate the hippocampal formation in generating responses to stimuli that are potentially threatening. C1 [Chudasama, Yogita; Wright, Katherine S.; Murray, Elisabeth A.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Chudasama, Y (reprint author), McGill Univ, Dept Psychol, 1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada. EM yogita.chudasama@mcgill.ca OI Murray, Elisabeth/0000-0003-1450-1642 FU Intramural NIH HHS NR 45 TC 34 Z9 34 U1 0 U2 2 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 JUN 1 PY 2008 VL 63 IS 11 BP 1084 EP 1091 DI 10.1016/j.biopsych.2007.11.012 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 302ML UT WOS:000255972300012 PM 18191111 ER PT J AU Orvis, GD Jamin, SP Kwan, KM Mishina, Y Kaartinen, VM Huang, S Roberts, AB Umans, L Huylebroeck, D Zwijsen, A Wang, D Martin, JF Behringer, RR AF Orvis, G. D. Jamin, S. P. Kwan, K. M. Mishina, Y. Kaartinen, V. M. Huang, S. Roberts, A. B. Umans, L. Huylebroeck, D. Zwijsen, A. Wang, D. Martin, J. F. Behringer, R. R. TI Functional redundancy of TGF-beta family type receptors and receptor-smads in mediating anti-Mullerian hormone-induced Mullerian duct regression in the mouse SO BIOLOGY OF REPRODUCTION LA English DT Article DE AMH; AMHR2; female reproductive tract; male reproductive tract; Mullerian ducts; signal transduction; Wolffian duct ID SEXUAL DEVELOPMENT; WOLFFIAN DUCT; CONDITIONAL KNOCKOUT; SIGNALING PATHWAY; II RECEPTOR; MICE; EXPRESSION; GENE; CELL; MECHANISMS AB Amniotes, regardless of genetic sex, develop two sets of genital ducts: the Wolffian and Mulerian ducts. For normal sexual development to occur, one duct must differentiate into its corresponding organs, and the other must regress. In mammals, the Wolffian duct differentiates into the male reproductive tract, mainly the vasa deferentia, epididymides, and seminal vesicles, whereas the Mullerian duct develops into the four components of the female reproductive tract, the oviducts, uterus, cervix, and upper third of the vagina. In males, the fetal Leydig cells produce testosterone, which stimulates the differentiation of the Wolffian duct, whereas the Sertoli cells of the fetal testes express anti-Mullerian hormone, which activates the regression of the Mullerian duct. Anti-Mullerian hormone is a member of the transforming growth factor-beta (TGF-beta) family of secreted signaling molecules and has been shown to signal through the BMP pathway. It binds to its type II receptor, anti-Mullerian hormone receptor 2 (AMHR2), in the Mullerian duct mesenchyme and through an unknown mechanism(s); the mesenchyme induces the regression of the Mullerian duct mesoepithelium. Using tissue-specific gene inactivation with an Amhr2-Cre allele, we have determined that two TGF-beta type 1 receptors (Acvr1 and Bmpr1a) and all three BMP receptor-Smads (Smad1, Smad5, and Smad8) function redundantly in transducing the anti-Mullerian hormone signal required for Mullerian duct regression. Loss of these genes in the Mullerian duct mesenchyme results in male infertility due to retention of Mullerian duct derivatives in an otherwise virilized male. C1 [Orvis, G. D.; Martin, J. F.; Behringer, R. R.] Univ Texas Houston, Grad Sch Biomed Sci, Program Genes & Dev, Houston, TX 77030 USA. [Jamin, S. P.] Univ Paris 11, INSERM, U782, F-92140 Clamart, France. [Orvis, G. D.; Jamin, S. P.; Kwan, K. M.; Behringer, R. R.] Univ Texas MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [Kwan, K. M.] Chinese Univ Hong Kong, Dept Biol, Shatin, Hong Kong, Peoples R China. [Mishina, Y.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kaartinen, V. M.] Univ So Calif, Sabin Res Inst, Los Angeles, CA 90027 USA. [Huang, S.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Huang, S.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Roberts, A. B.] NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Umans, L.; Huylebroeck, D.; Zwijsen, A.] Katholieke Univ Leuven, VIB, Dept Mol & Dev Genet, B-3000 Louvain, Belgium. [Umans, L.; Huylebroeck, D.; Zwijsen, A.] Katholieke Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium. [Wang, D.; Martin, J. F.] Texas A&M Univ, Inst Biosci & Technol, Houston, TX 77030 USA. RP Behringer, RR (reprint author), Univ Texas Houston, Grad Sch Biomed Sci, Program Genes & Dev, Houston, TX 77030 USA. EM rrb@mdanderson.org RI Jamin, Soazik/F-6796-2015 FU NCI NIH HHS [CA09299, T32 CA009299]; NICHD NIH HHS [HD30284, R01 HD030284, R37 HD030284]; NIDCR NIH HHS [DE/HD12324]; PHS HHS [DEO13085] NR 51 TC 42 Z9 46 U1 0 U2 8 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 2008 VL 78 IS 6 BP 994 EP 1001 DI 10.1095/biolreprod.107.066605 PG 8 WC Reproductive Biology SC Reproductive Biology GA 303QY UT WOS:000256056800005 PM 18322278 ER PT J AU Plonsky, I Kingsley, DH Rashtian, A Blank, PS Zimmerberg, J AF Plonsky, Ilya Kingsley, David H. Rashtian, Afshin Blank, Paul S. Zimmerberg, Joshua TI Initial size and dynamics of viral fusion pores are a function of the fusion protein mediating membrane fusion SO BIOLOGY OF THE CELL LA English DT Article DE baculovirus GP64; influenza haemagglutinin; time-resolved admittance measurement; viral fusion ID HEMAGGLUTININ SURFACE-DENSITY; PLANAR BILAYER-MEMBRANES; N-GLYCOSYLATION PATHWAY; CELL-CELL FUSION; INFLUENZA HEMAGGLUTININ; BACULOVIRUS GP64; CONFORMATIONAL-CHANGE; ENVELOPE PROTEIN; INSECT CELLS; MAST-CELLS AB Background information. Protein-mediated merger of biological membranes, membrane fusion, is an important process. To investigate the role of fusogenic proteins in the initial size and dynamics of the fusion pore (a narrow aqueous pathway, which widens to finalize membrane fusion), two different fusion proteins expressed in the same cell line were investigated: the major glycoprotein of baculovirus Autographa californica (GP64) and the HA (haemagglutinin) of influenza X31. Results. The host Sf9 cells expressing these viral proteins, irrespective of protein species, fused to human RBCs (red blood cells) upon acidification of the medium. A high-time-resolution electrophysiological study of fusion pore conductance revealed fundamental differences in (i) the initial pore conductance; pores created by HA were smaller than those created by GP64; (ii) the ability of pores to flicker; only HA-mediated pores flickered; and (iii) the time required for pore formation; HA-mediated pores took much longer to form after acidification. Conclusion. HA and GP64 have divergent electrophysiological phenotypes even when they fuse identical membranes, and fusion proteins play a crucial role in determining initial fusion pore characteristics. The structure of the initial fusion pore detected by electrical conductance measurements is sensitive to the nature of the fusion protein. C1 [Plonsky, Ilya; Kingsley, David H.; Rashtian, Afshin; Blank, Paul S.; Zimmerberg, Joshua] NIH, Lab Cellular & Mol Biophys, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NIH, Lab Cellular & Mol Biophys, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov FU Intramural NIH HHS [ZIA HD001409-24] NR 55 TC 6 Z9 6 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD JUN PY 2008 VL 100 IS 6 BP 377 EP 386 DI 10.1042/BC20070040 PG 10 WC Cell Biology SC Cell Biology GA 308QZ UT WOS:000256406400005 PM 18208404 ER PT J AU Yu, BB AF Yu, Binbing TI A frailty mixture cure model with application to hospital readmission cata SO BIOMETRICAL JOURNAL LA English DT Article DE frailty; mixture cure model; recurrent event ID MULTIVARIATE SURVIVAL-DATA; FRACTION; TIME; ESTIMATORS; JACKKNIFE; BOOTSTRAP AB Mixture cure models have been utilized to analyze survival data with possible cure. This paper considers the inclusion of frailty into the mixture cure model to model recurrent event data with a cure fraction. An attractive feature of the proposed model is the allowance for heterogeneity in risk among those individuals experiencing the event of interest in addition to the incorporation of a cured component. Maximum likelihood estimates can be obtained using the Expectation Maximization algorithm and standard errors are calculated from the Bootstrap method. The model is applied to hospital readmission data among colorectal cancer patients. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,Suite 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU Intramural NIH HHS NR 30 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD JUN PY 2008 VL 50 IS 3 BP 386 EP 394 DI 10.1002/bimj.200710399 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 320TC UT WOS:000257256900005 PM 18217699 ER PT J AU Ruopp, MD Perkins, NJ Whitcomb, BW Schisterman, EF AF Ruopp, Marcus D. Perkins, Neil J. Whitcomb, Brian W. Schisterman, Enrique F. TI Youden index and optimal cut-point estimated from observations affected by a lower limit of detection SO BIOMETRICAL JOURNAL LA English DT Article DE Youden Index; ROC curve; sensitivity and specificity; optimal cut-point ID MEASUREMENT ERROR; ROC CURVES; POPULATIONS; PARAMETERS AB The receiver operating characteristic (ROC) curve is used to evaluate a biomarker's ability for classifying disease status. The Youden Index (J), the maximum potential effectiveness of a biomarker, is a common summary measure of the ROC curve. In biomarker development, levels may be unquantifiable below a limit of detection (LOD) and missing from the overall dataset. Disregarding these observations may negatively bias the ROC curve and thus J. Several correction methods have been suggested for mean estimation and testing; however, little has been written about the ROC curve or its summary measures. We adapt non-parametric (empirical) and semi-parametric (ROC-GLM [generalized linear model]) methods and propose parametric methods (maximum likelihood (ML)) to estimate J and the optimal cut-point (c*) for a biomarker affected by a LOD. We develop unbiased estimators of J and c* via ML for normally and gamma distributed biomarkers. Alpha level confidence intervals are proposed using delta and bootstrap methods for the ML, semi-parametric, and non-parametric approaches respectively. Simulation studies are conducted over a range of distributional scenarios and sample sizes evaluating estimators' bias, root-mean square error, and coverage probability; the average bias was less than one percent for ML and GLM methods across scenarios and decreases with increased sample size. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods. We address the limitations and usefulness of each method in order to give researchers guidance in constructing appropriate estimates of biomarkers' true discriminating capabilities. C1 [Ruopp, Marcus D.; Perkins, Neil J.; Whitcomb, Brian W.; Schisterman, Enrique F.] NICHHD, Natl Inst Hlth, Div Epidemiol Stat & Prevent Res, DHHS, Bethesda, MD 20892 USA. RP Schisterman, EF (reprint author), NICHHD, Natl Inst Hlth, Div Epidemiol Stat & Prevent Res, DHHS, 6100 Execut Blvd,7B03, Bethesda, MD 20892 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008761-05] NR 18 TC 123 Z9 124 U1 0 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD JUN PY 2008 VL 50 IS 3 BP 419 EP 430 DI 10.1002/bimj.200710415 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 320TC UT WOS:000257256900009 PM 18435502 ER PT J AU Pennell, ML Dunson, DB AF Pennell, Michael L. Dunson, David B. TI Nonparametric bayes testing of changes in a response distribution with an ordinal predictor SO BIOMETRICS LA English DT Article DE Dirichlet process; dose response; nonparametric Bayes; toxicology; trend test ID DIRICHLET PROCESSES; KOLMOGOROV-SMIRNOV; DOSE LEVELS; MODELS; REGRESSION; ALTERNATIVES; ORDERINGS; INFERENCE; MIXTURES; PRIORS AB In certain biomedical studies, one may anticipate changes in the shape of a response distribution across the levels of an ordinal predictor. For instance, in toxicology studies, skewness and modality might change as dose increases. To address this issue, we propose a Bayesian nonparametric method for testing for distribution changes across an ordinal predictor. Using a dynamic mixture of Dirichlet processes, we allow the response distribution to change flexibly at each level of the predictor. In addition, by assigning mixture priors to the hyperparameters, we can obtain posterior probabilities of no effect of the predictor and identify the lowest dose level for which there is an appreciable change in distribution. The method also provides a natural framework for performing tests across multiple outcomes. We apply our method to data from a genotoxicity experiment. C1 [Pennell, Michael L.] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA. [Dunson, David B.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Pennell, ML (reprint author), Ohio State Univ, Coll Publ Hlth, Div Biostat, B-115 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM mpennell@cph.osu.edu FU Intramural NIH HHS [Z01 ES040009-10]; NIEHS NIH HHS [R01 ES017240, R01 ES017436] NR 54 TC 9 Z9 9 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2008 VL 64 IS 2 BP 413 EP 423 DI 10.1111/j.1541-0420.2007.00885.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 302HN UT WOS:000255959500011 PM 17764484 ER PT J AU Albert, PS AF Albert, Paul S. TI Modeling longitudinal biomarker data from multiple assays that have different known detection limits SO BIOMETRICS LA English DT Article DE below the level of detection; linear mixed models; measurement error; random effects models; repeated measures data; simian immunodeficiency virus AB Assays to measure biomarkers are commonly subject to large amounts of measurement error and known detection limits. Studies with longitudinal biomarker measurements may use multiple assays in assessing outcome. I propose an approach for jointly modeling repeated measures of multiple assays when these assays are subject to measurement error and known lower detection limits. A commonly used approach is to perform an initial assay with a larger lower detection limit on all repeated samples, followed by only performing a second more expensive assay with a lower minimum level of detection when the initial assay value is below its lower limit of detection. I show how simply replacing the initial assay measurement with the second assay measurement may be a biased approach and investigate the performance of the proposed joint model in this situation. Additionally, I compare the performance of the joint model with an approach that only uses the initial assay measurements in analysis. Further, I consider alternative designs to only performing the second assay when the initial assay measurement is below its lower detection limit. Specifically, I show that one only needs to perform the second assay on a fraction of assays that are above the lower detection limit on the first assay to substantially increase the efficiency. Further, I show the efficiency advantages of performing the second assay at random without regard to the initial assay measurement over a design in which the second assay is only performed when the initial assay is below its lower limit of detection. The methodology is illustrated with a recent study examining the use of a vaccine in treating macaques with simian immunodeficiency virus. C1 NCI, Biomet Res Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Biomet Res Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov NR 10 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2008 VL 64 IS 2 BP 527 EP 537 DI 10.1111/j.1541-0420.2007.00886.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 302HN UT WOS:000255959500023 PM 17764483 ER PT J AU Simon, R AF Simon, Richard TI Simple, defensible sample sizes based on cost efficiency - Discussions SO BIOMETRICS LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIALS; PHASE-II TRIALS; SCREENING TRIALS; PILOT TRIALS; DESIGN; AGENTS; SERIES C1 NCI, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 22 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2008 VL 64 IS 2 BP 589 EP 591 DI 10.1111/j.1541-0420.2008.01004_4.x PG 3 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 302HN UT WOS:000255959500031 ER PT J AU Dunson, DB Park, JH AF Dunson, David B. Park, Ju-Hyun TI Kernel stick-breaking processes SO BIOMETRIKA LA English DT Article DE conditional density estimation; dependent Dirichlet process; kernel methods; nonparametric Bayes; mixture model; prediction rule; random partition ID PROCESS HIERARCHICAL-MODELS; PRODUCT PARTITION MODELS; CHAIN MONTE-CARLO; MIXTURE-MODELS; DIRICHLET; DISTRIBUTIONS; PRIORS AB We propose a class of kernel stick-breaking processes for uncountable collections of dependent random probability measures. The process is constructed by first introducing an infinite sequence of random locations. Independent random probability measures and beta-distributed random weights are assigned to each location. Predictor-dependent random probability measures are then constructed by mixing over the locations, with stick-breaking probabilities expressed as a kernel multiplied by the beta weights. Some theoretical properties of the process are described, including a covariate-dependent prediction rule. A retrospective Markov chain Monte Carlo algorithm is developed for posterior computation, and the methods are illustrated using a simulated example and an epidemiological application. C1 [Dunson, David B.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Park, Ju-Hyun] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Dunson, DB (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov; parkj3@niehs.nih.gov FU Intramural NIH HHS [Z01 ES040013-07] NR 29 TC 92 Z9 93 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 2008 VL 95 IS 2 BP 307 EP 323 DI 10.1093/biomet/asn012 PG 17 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 306SW UT WOS:000256269100004 PM 18800173 ER PT J AU Heredia-Moya, J Kirk, KL AF Heredia-Moya, Jorge Kirk, Kenneth L. TI Synthesis of beta-(S-methyl)thioaspartic acid and derivatives SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE unnatural amino acids; ribosomal protein; posttranslational modification; sufenylationl; selective deprotection ID STREPTOMYCIN-RESISTANT MUTANTS; RIBOSOMAL-PROTEIN S12; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; 70S RIBOSOME; POSTTRANSLATIONAL MODIFICATION; SUBUNIT; ANTIBIOTICS; ALDEHYDES; GENE AB beta-(S-Methyl)thioaspartic acid occurs as a posttranslational modi. cation at position 88 in Escherichia coli ribosomal protein S12, a position that is a mutational hotspot resulting in both antibiotic-resistant and antibiotic-sensitive phenotypes. Critical to research designed to determine the biological function of beta-(S-methyl) thioaspartic acid will be the availability of synthetic beta-(S-methyl) thioaspartic acid as well as derivatives designed for peptide incorporation. We report here the synthesis of beta-(S-methyl) thioaspartic acid and derivatives. The installation of the beta-methylthio moiety into the aspartic acid structure was accomplished by electrophilic sulfenylation of N-protected-L-aspartic acid derivatives with 2,4-dinitrophenyl methyl disulfide. Following this key transformation, we were able to prepare protected beta-(S-methyl) thioaspartic acid derivative suitable for peptide coupling. Published by Elsevier Ltd. C1 [Heredia-Moya, Jorge; Kirk, Kenneth L.] NIDDKD, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov FU Intramural NIH HHS [Z01 DK031134-01] NR 26 TC 2 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2008 VL 16 IS 11 BP 5908 EP 5913 DI 10.1016/j.bmc.2008.04.069 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 308HD UT WOS:000256378200008 PM 18468905 ER PT J AU Uto, Y Nagasawa, H Jin, CZ Nakayama, S Tanaka, A Kiyoi, S Nakashima, H Shimamura, M Inayama, S Fujiwara, T Takeuchi, Y Uehara, Y Kirk, KL Nakata, E Hori, H AF Uto, Yoshihiro Nagasawa, Hideko Jin, Cheng-Zhe Nakayama, Shinichi Tanaka, Ayako Kiyoi, Saori Nakashima, Hitomi Shimamura, Mariko Inayama, Seiichi Fujiwara, Tomoya Takeuchi, Yoshio Uehara, Yoshimasa Kirk, Kenneth L. Nakata, Eiji Hori, Hitoshi TI Design of antiangiogenic hypoxic cell radiosensitizers: 2-Nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE hypoxic cell radiosensitizers; antiangiogenic agents; 2-aminomethylene-4-cyclopentene-1,3-dione; protein tyrosine kinase ID KINASE INHIBITOR; ANGIOGENESIS; GROWTH; SYSTEM AB We designed chiral 2-nitroimidazole derivatives containing a 2-aminomethylene- 4-cyclopentene-1,3-dione moiety as antiangiogenic hypoxic cell radiosensitizers. Based on results of molecular orbital calculations, the 2-aminomethylene-4-cyclopentene1,3-dione moiety is expected to show high electrophilicity comparable to that of the 2-methylene-4-cyclopentene-1,3-dione moiety included in TX-1123 and tyrphostin AG17. We evaluated the antiangiogenic and radiosensitizing effects of the new compounds, along with other biological properties including their activities as hypoxic cytotoxicities and protein tyrosine kinase (PTK) inhibitory activities. Among the compounds tested, 5 (TX-2036) proved to be the strongest antiangiogenic hypoxic cell radiosensitizer. All the other chiral 2-nitroimidazole derivatives having 2-aminomethylene-4-cyclopentene-1,3-dione moiety tested were also antiangiogenic hypoxic cell radiosensitizers. The PTK inhibitory activity of 5 (TX-2036) showed this to be a promising and potent EGFR kinase inhibitor, having an IC(50) value of lower than 2 mu M. This compound also was an Flt-1 kinase inhibitor having an IC(50) value of lower than 20 mu M. Our results show that these chiral 2- nitroimidazole derivatives that contain the 2- aminomethylene-4- cyclopentene1,3-dione moiety as a potent antiangiogenic pharmacophoric descriptor are promising lead candidates for the development of antiangiogenic hypoxic cell radiosensitizers. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Uto, Yoshihiro; Nagasawa, Hideko; Jin, Cheng-Zhe; Nakayama, Shinichi; Tanaka, Ayako; Kiyoi, Saori; Nakashima, Hitomi; Nakata, Eiji; Hori, Hitoshi] Univ Tokushima, Dept Life Syst, Inst Sci & Technol, Grad Sch, Tokushima 7708506, Japan. [Nagasawa, Hideko] Gifu Pharmaceut Univ, Lab Pharmaceut Chem, Gifu 5028585, Japan. [Shimamura, Mariko] Tokyo Metropolitan Inst Med Sci, Med Res & Dev Ctr, Bunkyo Ku, Tokyo 1138613, Japan. [Inayama, Seiichi] Inst Oriental Med Sci, Shibuya Ku, Tokyo 1550021, Japan. [Fujiwara, Tomoya; Takeuchi, Yoshio] Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan. [Uehara, Yoshimasa] Natl Inst Hlth, Dept Bioact Mol, Shinjuku Ku, Tokyo 1628640, Japan. [Kirk, Kenneth L.] NIDDKD, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. RP Hori, H (reprint author), Univ Tokushima, Dept Life Syst, Inst Sci & Technol, Grad Sch, Minamijasanjimacho 2, Tokushima 7708506, Japan. EM hori@bio.tokushima-u.ac.jp RI Nakata, Eiji/G-5523-2013 OI Nakata, Eiji/0000-0001-9564-6805 FU Intramural NIH HHS [Z01 DK031134-01] NR 18 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2008 VL 16 IS 11 BP 6042 EP 6053 DI 10.1016/j.bmc.2008.04.041 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 308HD UT WOS:000256378200022 PM 18474428 ER PT J AU Koda, Y Del Borgo, M Wessling, ST Lazarus, LH Okada, Y Toth, I Blanchfield, JT AF Koda, Yasuko Del Borgo, Mark Wessling, Susanne T. Lazarus, Lawrence H. Okada, Yoshio Toth, Istvan Blanchfield, Joanne T. TI Synthesis and in vitro evaluation of a library of modified endomorphin 1 peptides SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE endomorphin 1; opioid peptides; lipoamino acids; liposaccharides; drug delivery; oral peptide delivery ID BLOOD-BRAIN-BARRIER; MU-OPIOID RECEPTOR; NEUROBLASTOMA SH-SY5Y CELLS; EPITHELIAL CACO-2 CELLS; AMINE PROTECTING GROUP; SOLID-PHASE; NEUROPATHIC PAIN; ENKEPHALIN ANALOGS; DELIVERY-SYSTEMS; ORAL ABSORPTION AB Endomorphin 1 (Endo-1 = Tyr-Pro-Trp-Phe-NH(2)), an endogenous opioid with high affinity and selectivity for mu-opioid receptors, mediates acute and neuropathic pain in rodents. To overcome metabolic instability and poor membrane permeability, the N- and C-termini of Endo-1 were modified by lipoamino acids (Laa) and/or sugars, and 2',6'-dimethyltyrosine (Dmt) replacement of Tyr. Analogues were assessed for mu-opioid receptor affinity, inhibition of cAMP accumulation, enzymatic stability, and permeability across Caco-2 cell monolayers. C-Terminus modi. cation decreased receptor affinity, while N-terminus C8-Laa improved stability and permeability with slight change in receptor affinity. Dmt provided a promising lead compound: [C8Laa-Dmt[1]]-Endo-1 is nine times more stable (t(1/2) = 43.5 min), >8- fold more permeable in Caco-2 cell monolayers, and exhibits 140-fold greater mu-opioid receptor affinity (K(i mu) = 0.08 nM). (C) 2008 Elsevier Ltd. All rights reserved. C1 [Del Borgo, Mark; Wessling, Susanne T.; Toth, Istvan; Blanchfield, Joanne T.] Univ Queensland, Sch Mol & Microbial Sci, St Lucia, Qld 4072, Australia. [Koda, Yasuko; Toth, Istvan] Univ Queensland, Sch Pharm, St Lucia, Qld 4072, Australia. [Lazarus, Lawrence H.] NIEHS, Lab Parmacol & Chem, Res Triangle Pk, NC 27709 USA. [Okada, Yoshio] Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan. RP Blanchfield, JT (reprint author), Univ Queensland, Sch Mol & Microbial Sci, St Lucia, Qld 4072, Australia. EM j.blanchfield@uq.edu.au RI Toth, Istvan/C-1965-2013; Blanchfield, Joanne/C-1725-2014 OI Blanchfield, Joanne/0000-0003-1338-7446 FU Intramural NIH HHS [Z01 ES090053-20, Z01 ES100472-06, Z99 ES999999] NR 72 TC 38 Z9 38 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2008 VL 16 IS 11 BP 6286 EP 6296 DI 10.1016/j.bmc.2008.04.020 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 308HD UT WOS:000256378200045 PM 18468445 ER PT J AU Savitz, JB van der Merwe, L Stein, DJ Solms, M Ramesar, RS AF Savitz, Jonathan B. van der Merwe, Lize Stein, Dan J. Solms, Mark Ramesar, Rajkumar S. TI Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma SO BIPOLAR DISORDERS LA English DT Article DE alcohol abuse; bipolar disorder; childhood trauma; cognition; genetics; major depression; medication; memory; neuropsychology ID POSTTRAUMATIC-STRESS-DISORDER; DECLARATIVE MEMORY IMPAIRMENT; SEXUAL-ABUSE; HIPPOCAMPAL VOLUME; NEUROCOGNITIVE FUNCTION; COGNITIVE FUNCTION; EUTHYMIC PATIENTS; I DISORDER; UNIPOLAR DEPRESSION; MAJOR DEPRESSION AB Introduction: Impaired executive and memory function is a putative genetic trait marker of bipolar I disorder (BPD I). Although executive/memory function has been posited to be an endophenotype of BPD I, it is unclear whether this extends to bipolar spectrum illness. It is also unclear to what extent non-genetic factors such as childhood abuse, alcoholism and medication influence neurocognitive function. We assessed the neuropsychological performance of a large cohort of bipolar disorder probands and their affectively ill and healthy family members, while controlling for self-reported childhood sexual and emotional abuse, emotional neglect, alcohol abuse and medication. Methods: A total of 230 largely euthymic participants from 47 families, comprising 49 subjects with BPD I, 19 with bipolar II disorder (BPD II), 44 with recurrent major depression (MDE-R), 33 with a single lifetime episode of depression (MDE-S), 20 with other DSM-IV diagnoses and 65 unaffected relatives, were assessed with a battery of neuropsychological tasks. Results: Sexual abuse, emotional abuse and emotional neglect scores were associated with poorer cognitive performance. After controlling for childhood trauma, the BPD I group performed worse than unaffected relatives on tests of visual recall memory as well as verbal recall and recognition memory. In contrast, individuals with BPD II and bipolar spectrum illness did not differ significantly from unaffected relatives. Treatment with lithium and antipsychotic medication was associated with reduced executive and verbal recognition memory function. After controlling for medication and other covariates, only verbal recall memory was significantly impaired in the BPD I cohort. Conclusions: Verbal recall deficits may be one manifestation of a genetically driven dysfunction of frontal-striatal cortical networks in BPD I. C1 [Savitz, Jonathan B.; Ramesar, Rajkumar S.] Univ Cape Town, Inst Infect Dis & Mol Med, Div Human Genet, ZA-7700 Rondebosch, South Africa. [van der Merwe, Lize] Univ Cape Town, Biostat Unit, Med Res Council S Africa, ZA-7925 Cape Town, South Africa. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. [Solms, Mark] Univ Cape Town, Dept Psychol, ZA-7925 Cape Town, South Africa. [Solms, Mark] Univ Cape Town, Dept Neurol, ZA-7925 Cape Town, South Africa. RP Savitz, JB (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Rm 200,B15K,N Dr, Bethesda, MD 20892 USA. EM savitzj@mail.nih.gov RI Savitz, Jonathan/C-3088-2009; Ramesar, Raj/I-6941-2015; Stein, Dan/A-1752-2008 OI Savitz, Jonathan/0000-0001-8143-182X; Ramesar, Raj/0000-0001-5688-1634; Stein, Dan/0000-0001-7218-7810 NR 67 TC 50 Z9 51 U1 2 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2008 VL 10 IS 4 BP 479 EP 494 DI 10.1111/j.1399-5618.2008.00591.x PG 16 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 295LL UT WOS:000255475900004 PM 18452444 ER PT J AU Chapin, RE Adams, J Boekelheide, K Gray, LE Hayward, SW Lees, PSJ McIntyre, BS Portier, KM Schnorr, TM Selevan, SG Vandenbergh, JG Woskie, SR AF Chapin, Robert E. Adams, Jane Boekelheide, Kim Gray, L. Earl, Jr. Hayward, Simon W. Lees, Peter S. J. McIntyre, Barry S. Portier, Kenneth M. Schnorr, Teresa M. Selevan, Sherry G. Vandenbergh, John G. Woskie, Susan R. TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID ESTROGEN-RECEPTOR-ALPHA; PERFORMANCE LIQUID-CHROMATOGRAPHY; BREAST-CANCER CELLS; SPRAGUE-DAWLEY RATS; MEDAKA ORYZIAS-LATIPES; IN-UTERO EXPOSURE; ENDOCRINE-DISRUPTING COMPOUNDS; CARP CYPRINUS-CARPIO; CALBINDIN-D-9K MESSENGER-RNA; POLYCARBONATE BABY BOTTLES C1 [Chapin, Robert E.] Pfizer Inc, Groton, CT 06340 USA. [Adams, Jane] Univ Massachusetts, Boston, MA 02125 USA. [Boekelheide, Kim] Brown Univ, Providence, RI 02912 USA. [Gray, L. Earl, Jr.] US EPA, Res Triangle Pk, NC 27711 USA. [Hayward, Simon W.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Lees, Peter S. J.] Johns Hopkins Univ, Baltimore, MD USA. [McIntyre, Barry S.] Schering Plough Corp, Res Inst, Summit, NJ USA. [Portier, Kenneth M.] Amer Canc Soc, Atlanta, GA 30329 USA. [Schnorr, Teresa M.] NIOSH, Cincinnati, OH 45226 USA. [Selevan, Sherry G.] US Publ Hlth Serv Ret, Silver Spring, MD USA. [Vandenbergh, John G.] N Carolina State Univ, Raleigh, NC 27695 USA. [Woskie, Susan R.] Univ Massachusetts, Lowell, MA USA. RP Chapin, RE (reprint author), Care Of Shelby MD, NIEHS, EC-32,POB 12233, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 533 TC 209 Z9 221 U1 5 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-9733 EI 1542-9741 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2008 VL 83 IS 3 BP 157 EP 395 DI 10.1002/bdrb.20147 PG 239 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 323MC UT WOS:000257449200005 PM 18613034 ER PT J AU Hinrichs, CS Spolski, R Paulos, CM Gattinoni, L Kerstann, KW Palmer, DC Klebanoff, CA Rosenberg, SA Leonard, WJ Restifo, TP AF Hinrichs, Christian S. Spolski, Rosanne Paulos, Chrystal M. Gattinoni, Luca Kerstann, Keith W. Palmer, Douglas C. Klebanoff, Christopher A. Rosenberg, Steven A. Leonard, Warren J. Restifo, Nicholas P. TI IL-2 and IL-21 confer opposing differentiation programs to CD8(+) T cells for adoptive immunotherapy SO BLOOD LA English DT Article ID IN-VIVO; TUMOR-REGRESSION; TRANSFER THERAPY; HUMAN NAIVE; CANCER REGRESSION; TELOMERE LENGTH; STEM-CELLS; TH1 CELLS; B-CELLS; MEMORY AB IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8(+) T cells, but their distinct effects on antigen-driven differentiation of naive CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of Eomesodermin (Eomes) and maturation of naive CD8+ T cells into granzyme B- and CD44-expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8(+) T-cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2 impaired the subsequent antitumor function of transferred cells. Gene expression studies revealed a distinct IL-21 program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced antitumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8(+) T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies. C1 [Hinrichs, Christian S.; Paulos, Chrystal M.; Gattinoni, Luca; Kerstann, Keith W.; Palmer, Douglas C.; Klebanoff, Christopher A.; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Hinrichs, CS (reprint author), NCI, Surg Branch, NIH, Clin Res Ctr, Rm 3-5816, Bethesda, MD 20892 USA. EM christian_hinrichs@nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; Klebanoff, Christopher/D-9581-2011; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS NR 65 TC 196 Z9 206 U1 2 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 JUN 1 PY 2008 VL 111 IS 11 BP 5326 EP 5333 DI 10.1182/blood-2007-09-113050 PG 8 WC Hematology SC Hematology GA 307RR UT WOS:000256336500014 PM 18276844 ER PT J AU Cella, D Land, SR Chang, CH Day, R Costantino, JP Wolmark, N Ganz, PA AF Cella, David Land, Stephanie R. Chang, Chih-Hung Day, Richard Costantino, Joseph P. Wolmark, Norman Ganz, Patricia A. TI Symptom measurement in the Breast Cancer Prevention Trial (BCPT) (P-1): psychometric properties of a new measure of symptoms for midlife women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; breast cancer prevention; symptoms; scale; eight; menopausal; endocrine; NSABP; NHLBI (PEPI); BCPT; P-1 ID QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; TAMOXIFEN; NSABP AB Purpose: To evaluate scalability of a symptom scale administered to women enrolled in the Breast Cancer Prevention Trial (BCPT) (P-1) conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP).Patients and methods: Responses of 11,064 women recruited into a study of 20 mg daily tamoxifen versus placebo to prevent breast cancer in high-risk women were analyzed. Exploratory factor analyses of the 12 month data were conducted on a random subset of 4,000 women to estimate the factor structure. Baseline data on these same 4,000 women were analyzed to confirm the structure. The remaining sample was divided randomly into two data sets. Data on each set were then grouped by age (35-49, 50-59, or >= 60 years) and treatment (tamoxifen or placebo) to corroborate these analyses. Correlations between the obtained symptom clusters and two standard instruments (SF-36 and CES-D) were examined. Content analysis of open-ended responses was also conducted.Results: Eight clinically-interpretable clusters of symptoms were identified and confirmed: Cognitive symptoms, musculoskeletal pain, vasomotor symptoms, nausea, sexual problems, bladder problems, body image, and vaginal symptoms. Scoring for each scale represented by these eight clusters is provided. Content analysis of open-ended responses suggested four items that are additional candidates: fatigue, back problems, abdominal pain, and leg/foot cramps or pain. Conclusions: Symptoms associated with hormone therapy for breast cancer can vary. Nevertheless, the BCPT Eight Symptom Scale (BESS) can be clustered into clinically relevant and reproducible factors that may be useful in future outcomes research. C1 [Cella, David] Evanston Northwestern Healthcare, Ctr Outcomes Res & Educ, Evanston, IL 60201 USA. [Cella, David; Land, Stephanie R.; Chang, Chih-Hung; Day, Richard; Costantino, Joseph P.; Wolmark, Norman; Ganz, Patricia A.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Northwestern Univ, Inst Healthcare Studies, Evanston, IL USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. [Land, Stephanie R.; Costantino, Joseph P.] NSABP Biostat Ctr, Pittsburgh, PA USA. [Land, Stephanie R.; Day, Richard; Costantino, Joseph P.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Chang, Chih-Hung] Northwestern Univ, Buehler Ctr Aging Hlth & Soc, Feinberg Sch Med, Chicago, IL 60611 USA. [Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med & Publ Hlth, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Cella, D (reprint author), Evanston Northwestern Healthcare, Ctr Outcomes Res & Educ, 1001 Univ Pl,Suite 101, Evanston, IL 60201 USA. EM d-cella@northwestern.edu FU NCI NIH HHS [U10 CA069974, U10CA-69974, U10CA-37377, U10 CA037377] NR 25 TC 27 Z9 29 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2008 VL 109 IS 3 BP 515 EP 526 DI 10.1007/s10549-007-9682-9 PG 12 WC Oncology SC Oncology GA 300UY UT WOS:000255851900012 PM 17851765 ER PT J AU Hirt, C Schuler, F Kiefer, T Schwenke, C Haas, A Niederwieser, D Neser, S Assmann, M Srock, S Rohrberg, R Dachselt, K Leithauser, M Rabkin, CS Herold, M Dolken, G AF Hirt, Carsten Schueler, Frank Kiefer, Thomas Schwenke, Cornelia Haas, Antje Niederwieser, Dietger Neser, Sabine Assmann, Michael Srock, Stefanie Rohrberg, Robert Dachselt, Klaus Leithaeuser, Malte Rabkin, Charles S. Herold, Michael Doelken, Gottfried TI Rapid and sustained clearance of circulating lymphoma cells after chemotherapy plus rituximab: clinical significance of quantitative t(14;18) PCR monitoring in advanced stage follicular lymphoma patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE follicular lymphoma; rituximab; minimal residual disease; t(14;18); molecular remission ID POLYMERASE-CHAIN-REACTION; ANTI-CD20 MONOCLONAL-ANTIBODY; BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; NON-HODGKINS-LYMPHOMAS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HIGH-DOSE CHEMOTHERAPY; MULTICENTER PHASE-II; TERM-FOLLOW-UP; LOW-GRADE AB This study of first-line treatment in advanced-stage follicular lymphoma patients analysed the effects of MCP (mitoxantrone, chlorambucil and prednisolone) chemotherapy alone or in combination with rituximab (R-MCP) on circulating lymphoma cells (CLC) and assessed the prognostic value of a quantitative monitoring of CLC. CLC numbers were determined by quantitative polymerase chain reaction (PCR) for the t(14;18)-translocation or by allele-specific PCR for rearranged immunoglobulin heavy chain genes. We analysed blood samples from 43 patients treated in a randomized trial comparing eight cycles of MCP versus R-MCP. Clearance of CLC at the end of therapy was achieved in 21/25 patients (84%) treated with R-MCP compared with 0/18 after MCP alone (P < 0.0001). A >= 2 log CLC reduction was associated with a favourable clinical response (P = 0.0004) and prolonged event-free survival (P = 0.02). In R-MCP patients, stable CLC numbers or consistently PCR-negative blood samples were associated with a continuing clinical remission whereas in two patients a relapse was preceded by a >= 2 log CLC increase. This study demonstrated that R-MCP led to a rapid and sustained eradication of CLC and a >= 2 log CLC reduction was associated with a superior quality and duration of the clinical response. C1 [Hirt, Carsten; Schueler, Frank; Kiefer, Thomas; Schwenke, Cornelia; Doelken, Gottfried] Univ Klinikum Greifswald, Klin & Poliklin Innnere Med C, Hamatol & Onkol Transplatat Zentrum, D-17487 Greifswald, Germany. [Hirt, Carsten; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schwenke, Cornelia] Klinikum Ernst Von Bergmann, Potsdam, Germany. [Niederwieser, Dietger] Klinikum Univ Leipzig, Leipzig, Germany. [Neser, Sabine] Klinikium Chemnitz, Chemnitz, Germany. [Assmann, Michael] Krankenhaus Riesa, Berlin, Germany. [Srock, Stefanie] Charite Campus Virchow Klinikium, Berlin, Germany. [Rohrberg, Robert] Onkol Praxis, Halle, Germany. [Dachselt, Klaus] Sudharzkrankenhaus Nordhausen, Nordhausen, Germany. [Leithaeuser, Malte] Univ Rostock, Erfurt, Germany. [Herold, Michael] HELIOS Klin, Erfurt, Germany. RP Dolken, G (reprint author), Univ Klinikum Greifswald, Klin & Poliklin Innnere Med C, Hamatol & Onkol Transplatat Zentrum, D-17487 Greifswald, Germany. EM doelken@uni-greifswald.de FU Intramural NIH HHS NR 41 TC 22 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2008 VL 141 IS 5 BP 631 EP 640 DI 10.1111/j.1365-2141.2008.07101.x PG 10 WC Hematology SC Hematology GA 297UU UT WOS:000255643700008 PM 18422779 ER PT J AU Bagby, RM Quilty, LC Segal, ZV McBride, CC Kennedy, SH Costa, PT AF Bagby, R. Michael Quilty, Lena C. Segal, Zindel V. McBride, Carolina C. Kennedy, Sidney H. Costa, Paul T., Jr. TI Personality and differential treatment response in major depression: A randomized controlled trial comparing cognitive-behavioural therapy and pharmacotherapy SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE depression; psychotherapy; pharmacotherapy; personality; treatment selection ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; 5-FACTOR MODEL; NATIONAL-INSTITUTE; INTERPERSONAL PSYCHOTHERAPY; SELECTIVE ALTERATION; SELF-REPORTS; DISORDERS; METAANALYSIS; TRAITS AB Objective: Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method: Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result: Four personality traits-the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness-were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion: The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. C1 [Bagby, R. Michael; Segal, Zindel V.] Ctr Addict & Mental Hlth, Cognit Bahaviour Therapy Clin, Toronto, ON M5T 1R8, Canada. [Bagby, R. Michael; Segal, Zindel V.; Kennedy, Sidney H.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [McBride, Carolina C.] Ctr Addict & Mental Hlth, Interpersonal Therapy Clin, Toronto, ON M5T 1R8, Canada. [Kennedy, Sidney H.] Univ Hlth Network, Toronto, ON, Canada. [Costa, Paul T., Jr.] NIA, Chief Personal Stress & Coping Sect, Baltimore, MD 21224 USA. [Costa, Paul T., Jr.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Bagby, RM (reprint author), Ctr Addict & Mental Hlth, Cognit Bahaviour Therapy Clin, 250 Coll St, Toronto, ON M5T 1R8, Canada. EM michael_bagby@camh.net RI Segal, Zindel/F-8008-2014; OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [Z01 AG000184-19] NR 64 TC 63 Z9 64 U1 3 U2 22 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD JUN PY 2008 VL 53 IS 6 BP 361 EP 370 PG 10 WC Psychiatry SC Psychiatry GA 318ZG UT WOS:000257130700005 PM 18616856 ER PT J AU Rowland, JH Stefanek, M AF Rowland, Julia H. Stefanek, Michael TI Introduction: Partnering to embrace the future of cancer survivorship research and care SO CANCER LA English DT Editorial Material ID PHYSICAL-ACTIVITY; DIAGNOSIS; SURVIVAL; INTERVENTION; PROSTATE; OUTCOMES; HEALTH C1 [Rowland, Julia H.] NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Bethesda, MD 20892 USA. [Stefanek, Michael] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30329 USA. RP Rowland, JH (reprint author), NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, 6116 Execut Blvd,Ste 404, Bethesda, MD 20892 USA. EM rowlandj@mail.nih.gov NR 50 TC 4 Z9 4 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 JUN 1 PY 2008 VL 112 IS 11 SU S BP 2523 EP 2528 DI 10.1002/cncr.23451 PG 6 WC Oncology SC Oncology GA 304TT UT WOS:000256132700001 PM 18428200 ER PT J AU Hesse, BK Arora, NK Beckjord, EB Rutten, LJF AF Hesse, Bradford K. Arora, Neeraj K. Beckjord, Ellen Burke Rutten, Lila J. Finney TI Information support for cancer survivors SO CANCER LA English DT Article DE cancer survivors; consumer health information; national survey; information seeking ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION; UNITED-STATES; SERVICE; SEEKING; CARE; BEHAVIOR; INTERNET; SCIENCE; ACCESS AB Survivors' information-seeking behavior has traditionally been documented through analysis of inquiries to hotlines and cancer information services. Data from these self-selected inquiries tend to be restricted to a time around diagnosis, and to those populations possessing the wherewithal and motivation to seek information actively. The current study used data from a general population survey to assess 1) the prevalence of information-seeking behavior among survivors in the general population, 2) characteristics of seekers versus non-seekers, 3) ratings of information-seeking experience, and 4) actual versus preferred sources of information. Data were analyzed from the 2005 administration of the Health Information National Trends Survey (HINTS). HINTS is a cross-sectional, random digit dial telephone survey, weighted to provide estimates for the general population. Nearly half of all Americans (48.7%) indicated that they have looked for cancer information from 1 source or another. Percentages were highest for those who have been touched by cancer (63.1% of cancer survivors and 54.6% of those with family histories) and lowest for those with no cancer history (27.6% of those with no history). Quality concerns topped the list of information-seeking experiences for those recalling the last time they looked. Patterns of information-seeking revealed a discrepancy between preferred and actual source when tracked over years since diagnosis. Information-seeking is prevalent among cancer survivors and does not diminish over time. Prescriptions are given for reengineering the information environment to improve long-term outcomes for survivors. C1 [Hesse, Bradford K.; Arora, Neeraj K.; Rutten, Lila J. Finney] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Beckjord, Ellen Burke] RAND Corp, Pittsburgh, PA USA. RP Hesse, BK (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7365,EPN 4068, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 FU NCI NIH HHS [N02-PC-15003] NR 50 TC 50 Z9 52 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 SU S BP 2529 EP 2540 DI 10.1002/cncr.23445 PG 12 WC Oncology SC Oncology GA 304TT UT WOS:000256132700002 PM 18428201 ER PT J AU Blank, TO Bellizzi, KM AF Blank, Thomas O. Bellizzi, Keith M. TI A gerontologic perspective on cancer and aging SO CANCER LA English DT Article DE aging; gerontology; oncology; quality of life; psychology; psychosocial aspects; survivors; prostate cancer ID QUALITY-OF-LIFE; STRESS-RELATED GROWTH; LONG-TERM; BREAST-CANCER; POSTTRAUMATIC GROWTH; PROSTATE-CANCER; SOCIOEMOTIONAL SELECTIVITY; PSYCHOLOGICAL ADJUSTMENT; MENTAL-HEALTH; SURVIVORS AB Most people diagnosed with cancer are aged > 65 years, and many diagnosed younger live to become older survivors. Geriatric oncology is becoming recognized as a specialty area within oncology. It focuses specifically on the functional impacts of the interplay of aging and cancer, including the role of comorbidities. Nevertheless, to the authors' knowledge, little attention has been given to cancer from a gerontologic and lifespan perspective, especially quality of life and psychologic impact. Research has shown that the amount and type of psychologic impact of cancer is highly variable and that part of that variation is related to age, in that older persons are often less affected in both negative and positive ways. Gerontologic concepts and empiric findings related to physical, psychologic, and social aging processes may serve as partial explanations for that age-related pattern. Important potential contributors include psychologic factors, such as changes in future time perspective and goals, as well as social ones, such as roles and previous experience. The result is a complex interplay of factors that vary across persons but are covaried with age. Empiric findings regarding 1-year to 8-year prostate cancer survivors illustrate the age differences and the differential impacts of age itself and comorbidity. The use of gerontologic concepts to explain the age-related impact of cancer will benefit both research and clinical practice by providing a means to target interventions more effectively by taking into account the psychologic and social changes that often accompany aging. C1 [Blank, Thomas O.] Univ Connecticut, Unit 2058, Storrs, CT 06269 USA. [Bellizzi, Keith M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. RP Blank, TO (reprint author), Univ Connecticut, Unit 2058, Storrs, CT 06269 USA. EM thomas.blank@uconn.edu NR 73 TC 50 Z9 50 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 SU S BP 2569 EP 2576 DI 10.1002/cncr23444 PG 8 WC Oncology SC Oncology GA 304TT UT WOS:000256132700005 PM 18428204 ER PT J AU Monti, DA Sufian, M Peterson, C AF Monti, Daniel A. Sufian, Meryl Peterson, Caroline TI Potential role of mind-body therapies in cancer Survivorship SO CANCER LA English DT Review DE cancer; complementary and alternative medicine; mind-body therapy ID QUALITY-OF-LIFE; METASTATIC BREAST-CANCER; STRESS REDUCTION PROGRAM; RANDOMIZED CONTROLLED-TRIAL; GROUP PSYCHOSOCIAL SUPPORT; ALTERNATIVE MEDICINE CAM; PROSTATE-CANCER; PSYCHOLOGICAL DISTRESS; TAI-CHI; SOCIAL SUPPORT AB The use of complementary and alternative medicine (CAM) by cancer survivors is high, particularly among those with psychosocial distress, poor quality of life, culturally based health beliefs, and those who experience health disparities in the mainstream healthcare system. As the number of cancer survivors continues to increase, so does the diversity of the survivorship population, making it increasingly important to understand and address the CAM culture in different survivor groups. Given the known communication barriers between cancer patients and their physicians regarding CAM, it would be useful for oncology providers to have a platform from which to discuss CAM-related issues. It is proposed that mind-body therapies with some basis in evidence could provide such a platform and also serve as a possible means of connecting cancer survivors to psychosocial supportive services. This article reviews a few mind-body therapies that may have particular relevance to cancer survivors, such as hypnosis and meditation practices. A theoretical foundation by which such therapies provide benefit is presented, with particular emphasis on self-regulation. C1 [Monti, Daniel A.; Peterson, Caroline] Thomas Jefferson Univ & Hosp, Myrna Brind Ctr Integrat Med, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Sufian, Meryl] NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Bethesda, MD 20892 USA. RP Monti, DA (reprint author), Thomas Jefferson Univ & Hosp, Myrna Brind Ctr Integrat Med, Kimmel Canc Ctr, 111 S 11th St,Suite 6215 Gibbon Bldg, Philadelphia, PA 19107 USA. EM daniel.monti@jefferson.edu NR 128 TC 19 Z9 19 U1 3 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 SU S BP 2607 EP 2616 DI 10.1002/cncr23443 PG 10 WC Oncology SC Oncology GA 304TT UT WOS:000256132700008 PM 18428193 ER PT J AU Freedman, ND Subar, AF Hollenbeck, AR Leitzmann, MF Schatzkin, A Abnet, CC AF Freedman, Neal D. Subar, Amy F. Hollenbeck, Albert R. Leitzmann, Michael F. Schatzkin, Arthur Abnet, Christian C. TI Fruit and vegetable intake and gastric cancer risk in a large United States prospective cohort study SO CANCER CAUSES & CONTROL LA English DT Article DE gastric cancer; fruits; vegetables; cohort ID ESOPHAGEAL; DIET; CONSUMPTION; CLASSIFICATION; METAANALYSIS; NUTRITION; JAPANESE; STOMACH; CARDIA; HAWAII AB Objective Fruit and vegetable intake may protect against gastric cancer incidence. Results from case-control studies have indicated an inverse association, but results from cohort studies are inconsistent. Methods We prospectively investigated the association in 490,802 participants of the NIH-AARP Diet and Health Study using Cox proportional hazards models adjusted for gastric cancer risk factors. We present hazard ratios (HR) and 95% confidence intervals (CI) per increase of one daily serving per 1,000 calories. Results During 2,193,751 person years, 394 participants were diagnosed with incident gastric cancer. We observed no significant associations between total fruit and vegetable intake (1.01, 0.95-1.08), fruit intake (1.04, 0.95-1.14), or vegetable intake (0.98, 0.88-1.08) and gastric cancer risk. Results did not vary by sex or anatomic subsite (cardia versus non-cardia). All 13 botanical subgroups examined had no significant associations with either anatomic sub-site. Conclusion We did not observe significant associations between overall fruit and vegetable intake and gastric cancer risk in this large prospective cohort study. C1 [Freedman, Neal D.; Leitzmann, Michael F.; Schatzkin, Arthur; Abnet, Christian C.] NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Rockville, MD 20852 USA. [Freedman, Neal D.] Natl Canc Inst, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD USA. [Subar, Amy F.] Natl Canc Inst, Div Canc Control & Populat Sci, NIH, DHHS, Rockville, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Freedman, ND (reprint author), NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015 OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098 FU Intramural NIH HHS NR 30 TC 22 Z9 22 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2008 VL 19 IS 5 BP 459 EP 467 DI 10.1007/s10552-007-9107-4 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 301CX UT WOS:000255875100004 PM 18166992 ER PT J AU Kelemen, LE Wang, SS Lim, UH Cozen, W Schenk, M Hartge, P Li, Y Rothman, N Davis, S Chanock, SJ Ward, MH Cerhan, JR AF Kelemen, Linda E. Wang, Sophia S. Lim, Unhee Cozen, Wendy Schenk, Maryjean Hartge, Patricia Li, Yan Rothman, Nathaniel Davis, Scott Chanock, Stephen J. Ward, Mary H. Cerhan, James R. TI Vegetables- and antioxidant-related nutrients, genetic susceptibility, and non-Hodgkin lymphoma risk SO CANCER CAUSES & CONTROL LA English DT Article DE brassicaceae; zinc; GST; OGG1; XRCC ID DNA-REPAIR GENES; LUNG-CANCER RISK; SUPEROXIDE-DISMUTASE POLYMORPHISM; OXIDE SYNTHASE GENE; BREAST-CANCER; CRUCIFEROUS VEGETABLES; HISTORY QUESTIONNAIRE; COLORECTAL-CANCER; UNITED-STATES; DIET AB Genetic susceptibility to DNA oxidation, carcinogen metabolism, and altered DNA repair may increase non-Hodgkin lymphoma (NHL) risk, whereas vegetables- and antioxidant-related nutrients may decrease risk. We evaluated the interaction of a priori-defined dietary factors with 28 polymorphisms in these metabolic pathways. Incident cases (n = 1,141) were identified during 1998-2000 from four cancer registries and frequency-matched to population-based controls (n = 949). We estimated diet-gene joint effects using two-phase semi-parametric maximum-likelihood methods, which utilized genotype data from all subjects as well as 371 cases and 311 controls with available diet information. Adjusted odds ratios (95% confidence intervals) were lower among common allele carriers with higher dietary intakes. For the GSTM3 3-base insertion and higher total vegetable intake, the risk was 0.56 (0.35-0.92, p interaction = 0.03); for GSTP1 A114V and higher cruciferous vegetable intake, the risk was 0.52 (0.34-0.81, p interaction = 0.02); for OGG1 S326C and higher daily zinc intake, the risk was 0.71 (0.47-1.08, p interaction = 0.04) and for XRCC3 T241M and higher green leafy vegetable intake, the risk was 0.63 (0.41-0.97, p interaction = 0.03). Calculation of the false positive report probability determined a high likelihood of falsely positive associations. Although most associations have not been examined previously with NHL, our results suggest the examined polymorphisms are not modifiers of the association between vegetable and zinc intakes and NHL risk. C1 [Kelemen, Linda E.; Cerhan, James R.] Mayo Clin & Mayo Fdn, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Wang, Sophia S.; Lim, Unhee; Hartge, Patricia; Li, Yan; Rothman, Nathaniel; Chanock, Stephen J.; Ward, Mary H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Cozen, Wendy] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Schenk, Maryjean] Karmanos Canc Inst, Epidemiol Sect, Detroit, MI USA. [Davis, Scott] Univ Washington, Sch Publ Hlth & Community Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Cerhan, JR (reprint author), Mayo Clin & Mayo Fdn, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM cerhan.james@mayo.edu OI Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS [Z01 CP010136-12]; NCI NIH HHS [N01 PC067009, N01-CP-67010, N02-PC-71105, R25 CA092049, R25 CA92049-03, N01 PC065064, N01 PC067008, N01-PC-67009] NR 53 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2008 VL 19 IS 5 BP 491 EP 503 DI 10.1007/s10552-008-9111-3 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 301CX UT WOS:000255875100007 PM 18204928 ER PT J AU Lee, WJ Son, M Chun, BC Park, ES Lee, HK Coble, J Dosemeci, M AF Lee, Won Jin Son, Mia Chun, Byung Chul Park, Eun Sook Lee, Ha Kyung Coble, Joseph Dosemeci, Mustafa TI Cancer mortality and farming in South Korea: an ecologic study SO CANCER CAUSES & CONTROL LA English DT Article DE agriculture; cancer; farmers; mortality; regional difference; South Korea ID OCCUPATIONAL RISK-FACTORS; NON-HODGKINS-LYMPHOMA; WHEAT-PRODUCING STATES; HAIRY-CELL LEUKEMIA; AGRICULTURAL HEALTH; PROSTATE-CANCER; PESTICIDE APPLICATORS; GASTRIC-CANCER; BRAIN CANCER; FARMERS AB Objective The aim of this study was to examine the geographical difference of cancer mortality to determine any potential associations between cancer mortality and farming in South Korea. Methods We calculated standardized mortality ratios (SMRs) based on age- and gender-specific cancer mortality rates for 245 geographic areas, using the registered death data from 2000 to 2004 that were obtained from the Korea National Statistical Office. Using the data from the Agriculture Census in 1995, we obtained the farming index. Poisson regression analysis was used to evaluate the associations between cancer mortality and farming after adjustment for socioeconomic factors. Results The SMR analyses based on 62,403 annual average cancer deaths yielded regional variations for all cancers combined in men (SMR = 70-192) and women (SMR = 80-132). With increasing farming index we found significantly elevated cancer mortality of esophagus, stomach, brain, and leukemia for men, and of esophagus and stomach for women, whereas the SMR for colorectal and gall bladder cancers were inversely associated with farming. The results were similar when the analyses were repeated after the exclusion of metropolitan areas. Conclusions Our findings suggest a possible association between farming and mortality from a few cancer sites in South Korea. C1 [Lee, Won Jin; Chun, Byung Chul; Park, Eun Sook; Lee, Ha Kyung] Korea Univ, Dept Prevent Med, Coll Med, Seoul 136705, South Korea. [Son, Mia] Kangwon Univ, Dept Prevent Med, Coll Med, Chunchon, South Korea. [Coble, Joseph; Dosemeci, Mustafa] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Lee, WJ (reprint author), Korea Univ, Dept Prevent Med, Coll Med, Seoul 136705, South Korea. EM leewj@korea.ac.kr OI Chun, Byung Chul/0000-0001-6576-8916 NR 62 TC 9 Z9 9 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2008 VL 19 IS 5 BP 505 EP 513 DI 10.1007/s10552-008-9112-2 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 301CX UT WOS:000255875100008 PM 18197459 ER PT J AU Das, B Clegg, LX Feuer, EJ Pickle, LW AF Das, Barnali Clegg, Limin X. Feuer, Eric J. Pickle, Linda W. TI A new method to evaluate the completeness of case ascertainment by a cancer registry SO CANCER CAUSES & CONTROL LA English DT Article DE data quality; cancer; population registers; estimation techniques ID UNITED-STATES; SURVEILLANCE AB Background Epidemiologic research into cancer and subsequent decision making to reduce the cancer burden in the population are dependent on the quality of available data. The more reliable the data, the more confident we can be that the decisions made would have the desired effect in the population. The North American Association of Central Cancer Registries (NAACCR) certifies population-based cancer registries, ensuring uniformity of data quality. An important assessment of registry quality is provided by the index of completeness of cancer case ascertainment. NAACCR currently computes this index assuming that the ratio of cancer incidence rates to cancer mortality rates is constant across geographic areas within cancer site, gender, and race groups. NAACCR does not incorporate the variability of this index into the certification process. Methods We propose an improved method for calculating this index based on a statistical model developed at the National Cancer Institute to predict expected incidence using demographic and lifestyle data. We calculate the variance of our index using statistical approximation. Results We use the incidence model to predict the number of new incident cases in each registry area, based on all available registry data. Then we adjust the registry-specific expected numbers for reporting delay and data corrections. The proposed completeness index is the ratio of the observed number to the adjusted prediction for each registry. We calculate the variance of the new index and propose a simple method of incorporating this variability into the certification process. Conclusions Better modeling reduces the number of registries with unrealistically high completeness indices. We provide a fuller picture of registry performance by incorporating variability into the certification process. C1 [Das, Barnali] WESTAT Corp, Rockville, MD 20850 USA. [Clegg, Limin X.] Veterans Adm, Off Inspector Gen, Washington, DC USA. [Feuer, Eric J.] NCI, Stat Res & Appl Branch, Bethesda, MD 20892 USA. [Pickle, Linda W.] LLC, StarNet Consulting, Gaithersburg, MD USA. RP Das, B (reprint author), WESTAT Corp, 1650 Res Blvd, Rockville, MD 20850 USA. EM barnalidas@westat.com NR 18 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2008 VL 19 IS 5 BP 515 EP 525 DI 10.1007/s10552-008-9114-0 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 301CX UT WOS:000255875100009 PM 18270798 ER PT J AU Karagas, MR Villanueva, CM Nieuwenhuijsen, M Weisel, CP Cantor, KP Kogevinas, M AF Karagas, Margaret R. Villanueva, Cristina M. Nieuwenhuijsen, Mark Weisel, Cliff P. Cantor, Kenneth P. Kogevinas, Manolis TI Disinfection byproducts in drinking water and skin cancer? A hypothesis SO CANCER CAUSES & CONTROL LA English DT Letter C1 [Karagas, Margaret R.] Dartmouth Med Sch, Epidemiol & Biostat Sect, Dept Community & Family Med, Lebanon, NH 03756 USA. [Villanueva, Cristina M.; Nieuwenhuijsen, Mark; Kogevinas, Manolis] Inst Municipal Invest Med, Municipal Inst Med Res, Ctr Res Environm Epidemiol CREAL, E-08003 Barcelona, Spain. [Weisel, Cliff P.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Exposure Sci Div, Environm & Occupat Hlth Sci Inst, New Brunswick, NJ USA. [Cantor, Kenneth P.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Karagas, MR (reprint author), Dartmouth Med Sch, Epidemiol & Biostat Sect, Dept Community & Family Med, 1 Med Ctr Dr,7927 Rubin Bldg, Lebanon, NH 03756 USA. EM Margaret.R.Karagas@Dartmouth.Edu RI Villanueva, Cristina/N-1942-2014; Nieuwenhuijsen, Mark/C-3914-2017; Kogevinas, Manolis/C-3918-2017 OI Villanueva, Cristina/0000-0002-0783-1259; Nieuwenhuijsen, Mark/0000-0001-9461-7981; FU Intramural NIH HHS; NCI NIH HHS [R01 CA057494, R01CA57494]; NIEHS NIH HHS [P42 ES007373, P42 ES007373-140015, P42ES07373] NR 5 TC 7 Z9 7 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2008 VL 19 IS 5 BP 547 EP 548 DI 10.1007/s10552-008-9116-y PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 301CX UT WOS:000255875100012 PM 18219581 ER PT J AU Werner, S Mendoza, A Hilger, RA Erlacher, M Reichardt, W Lissat, A Konanz, C Uhl, M Niemeyer, CM Khanna, C Kontny, U AF Werner, Sebastian Mendoza, Arnulfo Hilger, Ralf A. Erlacher, Miriam Reichardt, Wilfried Lissat, Andrej Konanz, Claudia Uhl, Marcus Niemeyer, Charlotte M. Khanna, Chand Kontny, Udo TI Preclinical studies of treosulfan demonstrate potent activity in Ewing's sarcoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Ewing's sarcoma; treosulfan; busulfan; chemosensitivity; apoptosis; mouse; xenograft; pharmacokinetics ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; PREPARATIVE REGIMEN; INDUCED APOPTOSIS; OVARIAN-CANCER; TUMORS; BUSULFAN; BLOOD; RISK; CYTOTOXICITY AB Objectives High-dose chemotherapy with the alkylating agent busulfan has been widely used in the treatment of patients with high-risk Ewing's sarcoma. Because of risks for toxicity, busulfan and radiotherapy can not be applied together, leading to the omission of one effective therapy component. Treosulfan is a derivative of busulfan which has a lower side effect profile than busulfan and which can be used together with radiotherapy. We investigated the effect of treosulfan in a panel of Ewing's sarcoma cell lines on cell survival, cell cycle and apoptosis in vitro and compared it to busulfan. Furthermore, the anti-tumor effect of treosulfan was studied in an orthotopic Ewing's sarcoma mouse xenograft model. Methods Cell survival was measured by MTT assay and cell cycle analysis by flow cytometry. Apoptosis was analyzed via detection of DNA fragmentation, Hoechst 33258 staining, Annexin V, and cleavage of caspases-3 and 9. The effect of treosulfan and busulfan on primary tumor growth was assessed in Ewing's sarcoma xenografts in NOD/SCID mice (10 mice per group), pharmacokinetics of treosulfan were analyzed in nude mice. Results Treosulfan inhibited cell growth to at least 70% in all cell lines at concentrations achievable in vivo. Treosulfan had a greater effect on the inhibition of cell growth at equivalent concentrations compared to busulfan. The growth inhibitory effect of treosulfan at low concentrations was mainly due to a G2 cell cycle arrest, whereas at higher concentrations it was due to apoptosis. Apoptosis was induced at lower concentrations compared to busulfan. In contrast to busulfan, treosulfan induced cell death in an apoptosis-deficient cell line at concentrations achievable in vivo. In mice, treosulfan suppressed tumor growth at dosages of 2,500 and 3,000 mg/kg. Pharmacokinetic exposures of treosulfan in mice were similar to previous reports in human patients. At maximal tolerated dosages treosulfan had a higher anti-tumor activity than busulfan. Conclusions Our results suggest that treosulfan has efficacy against Ewing's sarcoma cells in vitro and in mice. Therefore, controlled trials examining the role of treosulfan in patients with Ewing's sarcoma are warranted. C1 [Werner, Sebastian; Erlacher, Miriam; Lissat, Andrej; Konanz, Claudia; Niemeyer, Charlotte M.; Kontny, Udo] Univ Freiburg, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, D-79106 Freiburg, Germany. [Mendoza, Arnulfo; Khanna, Chand] Natl Inst Hlth, Natl Canc Inst, Pedtai Oncol Branch, Bethesda, MD USA. [Hilger, Ralf A.] Univ Hosp Essen, Dept Internal Med, West German Canc Ctr, Essen, Germany. [Reichardt, Wilfried; Uhl, Marcus] Univ Freiburg, Dept Radiol, Freiburg, Germany. RP Kontny, U (reprint author), Univ Freiburg, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, Mathildenstr 1, D-79106 Freiburg, Germany. EM udo.kontny@uniklinik-freiburg.de RI Reichardt, Wilfried/K-6727-2013 NR 46 TC 19 Z9 19 U1 2 U2 4 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 JUN PY 2008 VL 62 IS 1 BP 19 EP 31 DI 10.1007/s00280-007-0566-9 PG 13 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 287ZP UT WOS:000254956300003 PM 17823799 ER PT J AU Safaeian, M Kiddugavu, M Gravitt, PE Gange, SJ Ssekasanvu, J Murokora, D Sklar, M Serwadda, D Wawer, MJ Shah, KV Gray, R AF Safaeian, Mahboobeh Kiddugavu, Mohammad Gravitt, Patti E. Gange, Stephen J. Ssekasanvu, Joseph Murokora, Dan Sklar, Marc Serwadda, David Wawer, Maria J. Shah, Keerti V. Gray, Ron TI Determinants of incidence and clearance of high-risk human papillomavirus infections in rural Rakai, Uganda SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT 23rd International Papillomavirus Conference and Clinical Workshop CY SEP 01-07, 2006 CL Prague, CZECH REPUBLIC ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE UNIVERSITY-STUDENTS; POLYMERASE-CHAIN-REACTION; CERVICAL-CANCER; NATURAL-HISTORY; SEROPOSITIVE WOMEN; COLLECTED SAMPLES; COLOMBIAN WOMEN; VAGINAL SWABS; YOUNG-WOMEN AB Background: We used self-administered vaginal swabs to assess the incidence and clearance of carcinogenic human papillomavirus (HPV) infections in rural Rakai, Uganda. Methods: Women provided self-administered vaginal swab at annual home-based visits. Type-specific carcinogenic HPV incidence and clearance and risk factors were assessed. Results: Carcinogenic HPV incidence was 17.3 per 100 person-years among HIV-positive women compared with 7.0 per 100 person-years among HIV-negative women (P < 0.001). HPV-51 had the highest incidence followed by HPV-16 (1.8 per 100 and 1.5 per 100 person-years, respectively). In multivariate model, HIV-positive women were twice as likely to have incident infection compared with HIV-negative women. Younger women were at higher risk for incident infection, as were women with higher lifetime and recent sexual partners, and high perception of AIDS. Married women were less likely to have incident infection. Approximately half of all carcinogenic HPV infections cleared over the study follow-up of 3 years. HPV-31, HPV-35, and HPV-16 had the lowest clearance (16.7%, 27.9%, and 38.3%, respectively). In multivariate model, HIV-positive, women over 30 years with higher HPV viral, burden and more lifetime sex partners were less likely to clear infections. Conclusions: Self-collected vaginal swabs provide accurate HPV exposure assessment for studying HPV exposure and epidemiology and can be an important tool for research in populations unwilling to undergo pelvic exam. C1 [Safaeian, Mahboobeh; Gravitt, Patti E.; Gange, Stephen J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Wawer, Maria J.; Gray, Ron] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat & Family Hlth Studies, Baltimore, MD USA. [Shah, Keerti V.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Kiddugavu, Mohammad; Ssekasanvu, Joseph; Murokora, Dan; Serwadda, David] Rakai Hlth Sci Program, Entebbe, Uganda. [Kiddugavu, Mohammad; Ssekasanvu, Joseph; Murokora, Dan; Serwadda, David] Uganda Virus Res Inst, Entebbe, Uganda. [Sklar, Marc] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Serwadda, David] Makerere Univ, Inst Publ Hlth, Kampala, Uganda. RP Safaeian, M (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Executive Blvd,Suite 550, Rockville, MD 20852 USA. EM safaeianm@mail.nih.gov OI Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [T32 AI050056, T32AI50056]; NICHD NIH HHS [R01 HD038883, R01 HD038883-02S1] NR 40 TC 25 Z9 25 U1 0 U2 0 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 JUN PY 2008 VL 17 IS 6 BP 1300 EP 1307 DI 10.1158/1055-9965.EPI-07-2678 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 315PC UT WOS:000256890900002 PM 18559545 ER PT J AU Bobe, G Sansbury, LB Albert, PS Cross, AJ Kahle, L Ashby, J Slattery, ML Caan, B Paskett, E Iber, F Kikendall, JW Lance, P Daston, C Marshall, JR Schatzkin, A Lanza, E AF Bobe, Gerd Sansbury, Leah B. Albert, Paul S. Cross, Amanda J. Kahle, Lisa Ashby, Jason Slattery, Martha L. Caan, Bette Paskett, Electra Iber, Frank Kikendall, James Walter Lance, Peter Daston, Cassandra Marshall, James R. Schatzkin, Arthur Lanza, Elaine TI Dietary flavonoids and colorectal adenoma recurrence in the polyp prevention trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ACTIVATOR PROTEIN-1; CANCER CELLS; QUERCETIN; RISK; INTERVENTION; HEALTH; FIBER; TUMORIGENESIS; MODULATION; MECHANISMS AB Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non-steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; P-trend = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. C1 [Bobe, Gerd; Lanza, Elaine] NCI, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. [Bobe, Gerd] NCI, Canc Prevent Fellowship Program, Off Prevent, Bethesda, MD 20892 USA. [Sansbury, Leah B.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Cross, Amanda J.] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kahle, Lisa; Ashby, Jason] Informat Management Serv Inc, Rockville, MD USA. [Slattery, Martha L.] Univ Utah, Salt Lake City, UT USA. [Caan, Bette] Kaiser Fdn Res Inst, Oakland, CA 94609 USA. [Paskett, Electra] Ohio State Canc Ctr, Columbus, OH USA. [Iber, Frank] Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. [Kikendall, James Walter] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Lance, Peter] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Daston, Cassandra] Daston Commun, Chapel Hill, NC USA. [Marshall, James R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Bobe, G (reprint author), NCI, Lab Canc Prevent, Room 110,Bldg 576, Frederick, MD 21702 USA. EM gb246f@nih.gov RI Lance, Peter/I-2196-2014 OI Lance, Peter/0000-0003-2944-1881 FU Intramural NIH HHS [Z01 BC010025-12] NR 56 TC 54 Z9 60 U1 2 U2 14 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 JUN PY 2008 VL 17 IS 6 BP 1344 EP 1353 DI 10.1158/1055-9965.EPI-07-0747 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 315PC UT WOS:000256890900008 PM 18559549 ER PT J AU Vareed, SK Kakarala, M Ruffin, MT Crowell, JA Normolle, DP Djuric, Z Brenner, DE AF Vareed, Shaiju K. Kakarala, Madhuri Ruffin, Mack T. Crowell, James A. Normolle, Daniel P. Djuric, Zora Brenner, Dean E. TI Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NF-KAPPA-B; CHEMOPREVENTIVE AGENT CURCUMIN; GLUTATHIONE-S-TRANSFERASE; I CLINICAL-TRIAL; DIETARY CURCUMIN; COLON CARCINOGENESIS; CELL-PROLIFERATION; NATURAL-PRODUCTS; MOUSE EPIDERMIS; DRUG DISCOVERY AB Background: Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited. . Methods: This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a one-compartment absorption and elimination model. Results: Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only one subject had detectable free curcumin at any of the 14 time points assayed, but curcumin glucuronides and sulfates were detected in all subjects. Based on the pharmacokinetic model, the area under the curve for the 10 and 12 g doses was estimated (mean +/- SE) to be 35.33 +/- 3.78 and 26.57 +/- 2.97 mu g/mL x h, respectively, whereas C-max was 2.30 +/- 0.26 and 1.73 +/- 0.19 mu g/mL. The T-max and t(1/2) were estimated to be 3.29 +/- 0.43 and 6.77 +/- 0.83 h. The ratio of glucuronide to sulfate was 1.92:1. The curcumin conjugates were present as either glucuronide or sulfate, not mixed conjugates. Conclusion: Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma. C1 [Brenner, Dean E.] Univ Michigan, Sch Med, Dept Internal Med, Med Ctr,Canc Ctr 2150, Ann Arbor, MI 48109 USA. [Ruffin, Mack T.; Djuric, Zora] Univ Michigan, Sch Med, Dept Family Med, Ann Arbor, MI 48109 USA. [Normolle, Daniel P.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Normolle, Daniel P.] Vet Affairs Med Ctr, Ann Arbor, MI USA. [Crowell, James A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Brenner, DE (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Med Ctr,Canc Ctr 2150, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM dbrenner@med.umich.edu RI Djuric, Zora/H-5147-2013; OI Djuric, Zora/0000-0002-8886-8853; Normolle, Daniel/0000-0001-8675-5014; Ruffin, Mack/0000-0001-8336-478X FU NCI NIH HHS [CN-55124, N01CN35110]; NCRR NIH HHS [M01 RR000042, M01-RR00024] NR 50 TC 144 Z9 144 U1 4 U2 28 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 JUN PY 2008 VL 17 IS 6 BP 1411 EP 1417 DI 10.1158/1055-9965.EPI-07-2693 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 315PC UT WOS:000256890900017 PM 18559556 ER PT J AU Shou, JZ Hu, N Takikita, M Roth, MJ Johnson, LL Giffen, C Wang, QH Wang, CY Wang, Y Su, H Kong, LH Emmert-Buck, MR Goldstein, AM Hewitt, SM Taylor, PR AF Shou, Jian-Zhong Hu, Nan Takikita, Mikiko Roth, Mark J. Johnson, Laura Lee Giffen, Carol Wang, Quan-Hong Wang, Chaoyu Wang, Yuan Su, Hua Kong, Li-Hui Emmert-Buck, Michael R. Goldstein, Alisa M. Hewitt, Stephen M. Taylor, Philip R. TI Overexpression of CDC25B and LAMC2 mRNA and protein in esophageal squamous cell carcinomas and premalignant lesions in subjects from a high-risk population in China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN COLORECTAL-CARCINOMA; OVARIAN-CANCER PATIENTS; LAMININ GAMMA-2 CHAIN; TIME QUANTITATIVE PCR; POOR-PROGNOSIS; PROSTATE-CANCER; DNA-DAMAGE; N-MYC; EXPRESSION; PHOSPHATASES AB Molecular events associated with the initiation and progression of esophageal squamous cell carcinoma (ESCC) remain poorly understood but likely hold the key to effective early detection approaches for this almost invariably fatal cancer. CDC25B and LAMC2 are two promising early detection candidates emerging from new molecular studies of ESCC. To further elucidate the role of these two genes in esophageal carcinogenesis, we did a series of studies to (a) confirm RNA overexpression, (b) establish the prevalence of protein overexpression, (c) relate protein overexpression to survival, and (d) explore their potential as early detection biomarkers. Results of these studies indicated that CDC25B mRNA was overexpressed (>= 2-fold overexpression in tumor compared with normal) in 64% of the 73 ESCC cases evaluated, whereas LAMC2 mRNA was overexpressed in 89% of cases. CDC25B protein expression was categorized as positive in 59% (144 of 243) of ESCC cases on a tumor tissue microarray, and nonnegative LAMC2 patterns of protein expression were observed in 82% (225 of 275) of cases. Multivariate-adjusted proportional hazard regression models showed no association between CDC25B protein expression score and risk of death [hazard ratio (HR) for each unit increase in expression score, 1.00; P = 0.90]; however, several of the LAMC2 protein expression patterns strongly predicted survival. Using the cytoplasmic pattern as the reference (the pattern with the lowest mortality), cases with a diffuse pattern had a 254% increased risk of death (HR, 3.52; P = 0.007), cases with no LAMC2 expression had a 169% increased risk of death (HR, 2.69; P = 0.009), and cases with a peripheral pattern had a 130% greater risk of death (HR, 2.30; P = 0.02). CDC25B protein expression scores in subjects with esophageal biopsies diagnosed as normal (n = 35), dysplastic (n = 23), or ESCC (n = 32) increased significantly with morphologic progression. For LAMC2, all normal and dysplastic patients had a continuous pattern of protein expression, whereas all ESCCs showed alternative, noncontinuous patterns. This series of studies showed that both CDC25B and LAMC2 overexpress RNA and protein in a significant majority of ESCC cases. The strong relation of LAMC2 pattern of protein expression to survival suggests a role in prognosis, whereas the association of CDC25B with morphologic progression indicates a potential role as an early detection marker. C1 [Shou, Jian-Zhong] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100037, Peoples R China. [Hu, Nan; Wang, Chaoyu; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Takikita, Mikiko; Emmert-Buck, Michael R.; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Roth, Mark J.] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Johnson, Laura Lee] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA. [Wang, Quan-Hong; Wang, Yuan; Kong, Li-Hui] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. RP Hewitt, SM (reprint author), NCI, Pathol Lab, Adv Technol Ctr, Bldg 10, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov; ptaylor@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS [Z01 CP000150-03] NR 48 TC 18 Z9 18 U1 0 U2 1 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 JUN PY 2008 VL 17 IS 6 BP 1424 EP 1435 DI 10.1158/1055-9965.EPI-06-0666 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 315PC UT WOS:000256890900019 PM 18559558 ER PT J AU Flood, A Mai, V Pfeiffer, R Kahle, L Rosen, CJ Lanza, E Schatzkin, A AF Flood, Andrew Mai, Volker Pfeiffer, Ruth Kahle, Lisa Rosen, Clifford J. Lanza, Elaine Schatzkin, Arthur TI Serum concentrations of insulin-like growth factor and insulin-like growth factor binding protein 3 and recurrent colorectal adenomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IGF-BINDING PROTEIN-3; FACTOR-I; CANCER-RISK; PLASMA-INSULIN; FACTOR (IGF)-I; C-PEPTIDE; WOMEN; MEN AB Insulin-like growth factor I (IGF-I) and its primary binding protein, IGFBP-3, have been associated with colorectal cancer incidence in prior epidemiologic studies. High concentrations of IGF-I generally result in increasing risk and high concentrations of IGFBP-3 in decreasing risk. Only one prior study of IGF-I and IGFBP-3 and adenoma recurrence has been reported. We assayed fasting serum from 375 subjects with and 375 subjects without a recurrent adenoma during the course of the Polyp Prevention Trial to determine baseline concentrations of IGF-I and IGFBP-3. To estimate relative risk of adenoma recurrence over the course of 4 years of follow-up for each of these serum measures, we calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression models adjusting for age, gender, body mass index, intervention group, aspirin, smoking, ethnicity, and education. For both IGF-I and IGFBP-3, we found trends indicating decreased risk for subjects in the high compared with the low quartile (for IGF-I: OR, 0.65; 95% CI 0.41-1.01; for IGFBP-3: OR, 0.66; 95% CI, 0.42-1.05). The associations were even greater for advanced adenomas (for IGF-I: OR, 0.51; 95% CI, 0.21-1.29; for IGFBP-3: OR, 0.32; 95% CI, 0.13-0.82). These results showed an unexpected null association, or even the suggestion of a reduction in risk for recurrent adenoma, with not just high IGFBP-3 concentration but also with high levels of IGF-I. Why IGF-I would decrease risk of recurrent adenoma (as distinct from incident adenoma or colorectal cancer) is not clear. C1 [Flood, Andrew] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Flood, Andrew] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55454 USA. [Mai, Volker] Univ Florida, Gainesville, FL USA. [Pfeiffer, Ruth] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lanza, Elaine] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Kahle, Lisa] Informat Management Serv Inc, Silver Spring, MD USA. [Rosen, Clifford J.] Maine Ctr Osteoporosis Res & Educ, Bangor, ME USA. RP Flood, A (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM flood009@umn.edu RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS; NCI NIH HHS [K07 CA108910-01A1, K07 CA108910] NR 19 TC 7 Z9 7 U1 0 U2 0 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 JUN PY 2008 VL 17 IS 6 BP 1493 EP 1498 DI 10.1158/1055-9965.EPI-08-0048 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 315PC UT WOS:000256890900027 PM 18559566 ER PT J AU Shamimi-Noori, S Yeow, WS Ziauddin, MF Xin, H Tran, TLN Xie, J Loehfelm, A Patel, P Yang, J Schrump, DS Fang, BL Nguyen, DM AF Shamimi-Noori, S. Yeow, W-S Ziauddin, M. F. Xin, H. Tran, T. L. N. Xie, J. Loehfelm, A. Patel, P. Yang, J. Schrump, D. S. Fang, B. L. Nguyen, D. M. TI Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway SO CANCER GENE THERAPY LA English DT Article DE adenovirus; lung cancer; mesothelioma; esophageal cancer; TRAIL; mitochondria ID TRAIL-INDUCED APOPTOSIS; REVERSE-TRANSCRIPTASE PROMOTER; THORACIC CANCER-CELLS; CASPASE ACTIVATION; CYTOCHROME-C; APO2L/TRAIL-MEDIATED CYTOTOXICITY; MEDIATED SENSITIZATION; BCL-2 OVEREXPRESSION; DECOY RECEPTORS; HTERT PROMOTER AB Despite adequately expressing tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL) receptors DR4/ DR5, malignant cells are frequently refractory to the cytotoxic effect of this apoptosis-inducing ligand. The susceptibility of cancer cells to TRAIL can be potentiated by cisplatin ( CDDP). This study was designed to evaluate the ability of cisplatin to enhance the cytotoxic effect of TRAIL gene therapy using the recombinant adenovirus-mediated tumor-selective expression of membrane-bound green fluorescence protein ( GFP)-TRAIL fusion protein ( AdVgTRAIL) on thoracic cancer cells and to elucidate the putative mechanisms responsible for this synergistic combination effect. While causing little death of cultured thoracic cancer cells by itself, AdVgTRAIL in combination with CDDP, on the other hand, mediated profound supra-additive cytotoxicity and apoptosis via a strong bystander effect. CDDP/ AdVgTRAIL-induced cytotoxicity was completely abrogated either by the pancaspase inhibitor zVAD-fmk or by the selective caspase 9 inhibitor or by transient knockdown of caspase 9 by siRNA, indicating that this process was caspase-mediated and mitochondria-dependent. This was confirmed by the observation that Bcl2 overexpression protected the cells from combination-induced cytotoxicity. Robust activation of caspase 8 activity in combination-treated cells was blocked by overexpression of Bcl2, indicating that caspase 8 activation was secondary to the mitochondria-mediated amplification feedback loop. Combining CDDP with AdVgTRAIL greatly enhances its tumoricidal efficacy in cultured thoracic cancer cells in vitro. The two agents interact to mediate profound activation of caspase cascade via recruitment of the mitochondria and positive feedback loop. The CDDP/ AdVgTRAIL combination also exhibits a strong antitumor effect in in vivo animal model of human cancer xenografts. C1 [Shamimi-Noori, S.; Yeow, W-S; Ziauddin, M. F.; Xin, H.; Tran, T. L. N.; Loehfelm, A.; Yang, J.; Schrump, D. S.] NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. [Xie, J.; Patel, P.] Natl Inst Hlth, Mol Imaging Lab, Bethesda, MD USA. [Fang, B. L.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Cardiovasc & Thorac Surg, Houston, TX 77030 USA. [Nguyen, D. M.] Univ Miami, Thorac Surg Sect, Div Cardiothorac Surg, DeWitt Daughtry Family Dept Surg,Jackson Mem Hosp, Miami, FL 33134 USA. RP Nguyen, DM (reprint author), Univ Miami, Thorac Surg Sect, Div Cardiothorac Surg, DeWitt Daughtry Family Dept Surg,Jackson Mem Hosp, ET 3072,1161 NW 12th St, Miami, FL 33134 USA. EM dnguyen4@med.miami.edu FU Intramural NIH HHS NR 52 TC 28 Z9 29 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUN PY 2008 VL 15 IS 6 BP 356 EP 370 DI 10.1038/sj.cgt.7701120 PG 15 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 300BQ UT WOS:000255799700002 PM 18309355 ER PT J AU Guan, M Tripathi, V Zhou, X Popescu, NC AF Guan, M. Tripathi, V. Zhou, X. Popescu, N. C. TI Adenovirus-mediated restoration of expression of the tumor suppressor gene DLC1 inhibits the proliferation and tumorigenicity of aggressive, androgen-independent human prostate cancer cell lines: prospects for gene therapy SO CANCER GENE THERAPY LA English DT Article DE deleted in liver cancer; prostate cancer; tumor suppressor gene; suppression of tumor cell proliferation; apoptosis; gene therapy ID HUMAN HEPATOCELLULAR-CARCINOMA; GTPASE-ACTIVATING PROTEIN; SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; CHROMOSOME 8P DELETION; BREAST-CANCER; IN-VIVO; METASTASIS; APOPTOSIS; RHO AB Our recent study showing highly recurrent loss of function of DLC1 ( deleted in liver cancer 1), a tumor suppressor gene in primary prostate carcinoma ( PCA), implicates this gene in the pathogenesis of this disease. To evaluate the response of PCA to oncosuppressive activity of DLC1, we examined now the effects of adenoviral vector for human DLC1 transduction into the DLC1-deficient, androgen-independent ( AI) and aggressive human PCA cell lines PC-3 and C4-2-B2. Adenovirus-mediated restoration of DLC1 expression inhibited the proliferation, invasiveness and anchorage-independent growth of PC-3 and C4-2-B2 cells in vitro as well as the tumorigenicity of PC-3 cells in nude mice. It also induced cell-cycle arrest, inhibited the activation of RhoA and the formation of actin stress fibers. DLC1 induced apoptosis in C4-2-B2 cells, whereas it did not elicit such an effect in PC-3 cells. The abundance of the antiapoptotic protein Bcl-2 was greater in PC-3 cells than in C4-2-B2 cells, and PC-3 cells were rendered sensitive to DLC1-induced apoptosis by treatment with the Bcl-2 inhibitor HA14-1. These results suggest that adenovirus-mediated DLC1 transfer, alone or together with other agents, such as inhibitors of Bcl-2 or histone deacetylase, might prove effective in the treatment of aggressive, AI-PCA. C1 [Guan, M.; Tripathi, V.; Zhou, X.; Popescu, N. C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 4128,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov FU Intramural NIH HHS NR 41 TC 22 Z9 22 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUN PY 2008 VL 15 IS 6 BP 371 EP 381 DI 10.1038/cgt.2008.13 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 300BQ UT WOS:000255799700003 PM 18369381 ER PT J AU Park, JM Terabe, M Donaldson, DD Forni, G Berzofsky, JA AF Park, Jong Myun Terabe, Masaki Donaldson, Debra D. Forni, Guido Berzofsky, Jay A. TI Natural immunosurveillance against spontaneous, autochthonous breast cancers revealed and enhanced by blockade of IL-13-mediated negative regulation SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE IL-13; breast cancer; immunosurveillance ID ALPHA-GALACTOSYLCERAMIDE KRN7000; HER-2/NEU TRANSGENIC MICE; T-CELLS; TUMOR IMMUNOSURVEILLANCE; NKT CELLS; ANTITUMOR IMMUNITY; MAMMARY-CARCINOMA; DENDRITIC CELLS; IFN-GAMMA; PHASE-I AB We and others previously observed immunosurveillance against transplantable tumors in mice, and enhancement thereof by blockade of negative regulation by T reg cells or the NKT-IL-13-myeloid cell-TGF-beta regulatory circuit. However, it was unknown whether natural immunosurveillance inhibits growth of completely spontaneous autochthonous tumors, and whether it can be improved by inhibition of negative regulation. To examine the existence of T cell-mediated immunosurveillance against spontaneous tumors, BALB-neuT mice were treated with anti-CD4 and/or anti-CD8. A role for IL-13 in the suppression of immunosurveillance was investigated by treating mice with IL-13 inhibitor. We show that even spontaneous autochthonous breast carcinomas arising in Her-2/neu transgenic mice appear more quickly when the mice are depleted of T cells, evidence for T-cell mediated immunosurveillance slowing tumor growth. This immunosurveillance could be further enhanced by blockade of IL-13 (but not IL-4) which slowed the appearance of these autologous tumors compared to control antibody-treated mice. Thus, even completely spontaneous, autochthonous breast cancers can be controlled in part by natural immunosurveillance, and blockade of negative regulation can improve this control. C1 [Park, Jong Myun; Terabe, Masaki; Berzofsky, Jay A.] NIH, Vaccine Branch, Ctr Canc Res, Natl Canc Inst, Bethesda, MD 20892 USA. [Donaldson, Debra D.] Wyeth Res, Cambridge, MA USA. [Forni, Guido] Univ Turin, Ctr Mol Biotechnol, Dept Clin & Biol Sci, Turin, Italy. RP Terabe, M (reprint author), NIH, Vaccine Branch, Ctr Canc Res, Natl Canc Inst, Bldg 10-Room 6B-12,9000 Rockville Pk, Bethesda, MD 20892 USA. EM terabe@mail.nih.gov FU Intramural NIH HHS NR 34 TC 22 Z9 22 U1 0 U2 2 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 JUN PY 2008 VL 57 IS 6 BP 907 EP 912 DI 10.1007/s00262-007-0414-0 PG 6 WC Oncology; Immunology SC Oncology; Immunology GA 280BY UT WOS:000254401100013 PM 18004566 ER PT J AU Cho, NL Redston, M Zauber, AG Carothers, AM Hornick, J Wilton, A Sontag, S Nishioka, N Giardiello, FM Saltzman, JR Gostout, C Eagle, CJ Hawk, ET Bertagnolli, MM AF Cho, Nancy L. Redston, Mark Zauber, Ann G. Carothers, Adelaide M. Hornick, Jason Wilton, Andrew Sontag, Stephen Nishioka, Norman Giardiello, Francis M. Saltzman, John R. Gostout, Chris Eagle, Craig J. Hawk, Ernest T. Bertagnolli, Monica M. TI Aberrant Crypt Foci in the Adenoma Prevention with Celecoxib Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER; RAT COLON; CYCLOOXYGENASE-2 INHIBITOR; MURINE COLON; ASPIRIN; QUANTIFICATION; EXPRESSION; POLYPOSIS; FEATURES; LESIONS AB Aberrant crypt foci (ACF) are the earliest visible neoplastic lesions in the colorectum. The natural history of these lesions and their role in the adenoma-carcinoma sequence are unknown. We studied ACF in a subset of patients randomized to placebo (n = 17), celecoxib (200 mg twice daily; n = 15), or celecoxib (400 mg twice daily; n = 13) in the Adenoma Prevention with Celecoxib (APC) trial. Magnification chromoendoscopy was done to identify, count, and biopsy ACF within the rectum at baseline and after 8 to 12 months of treatment. A total of 655 ACF were identified in 45 patients. We examined 70 of these ACF histologically, and all 70 were nondysplastic. Cohort characteristics and APC trial treatment results for substudy patients were similar to those of the overall APC trial. There was no significant modulation of ACF by celecoxib (versus placebo; P = 0.77). Immunohistochemical comparison of ACF with adjacent normal mucosa showed that ACF had an increased proliferative index as determined by Ki-67 (P < 0.0001), but lacked other features of neoplasia such as increased cyclooxygenase-2 expression and microvessel density, nuclear localization of beta-catenin, or decreased expression of the tumor suppressors SMAD4, Estrogen Receptor alpha, or MGMT. Only baseline SMAD4 expression in ACF correlated with posttreatment adenoma recurrence (independent of treatment arm; P = 0.01). The presence or number of nondysplastic ACF did not correlate with a higher risk of synchronous advanced or recurrent adenomas. Our overall results indicated that nondysplastic ACF were not accurate surrogate endpoint biomarkers of recurrent colorectal adenomas in the APC trial. C1 [Cho, Nancy L.; Carothers, Adelaide M.; Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Redston, Mark; Hornick, Jason] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Saltzman, John R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hawk, Ernest T.] NCI, Bethesda, MD 20892 USA. [Gostout, Chris] Mayo Clin, Dept Med, Rochester, MN USA. [Giardiello, Francis M.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Sontag, Stephen] Edward Hines Vet Adm Med Ctr, Hines, IL 60141 USA. [Wilton, Andrew] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Eagle, Craig J.] Pfizer Inc, New York, NY USA. [Nishioka, Norman] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 31 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2008 VL 1 IS 1 BP 21 EP 31 DI 10.1158/1940-6207.CAPR-07-0011 PG 11 WC Oncology SC Oncology GA 417UQ UT WOS:000264104400006 PM 19138933 ER PT J AU Meyskens, FL McLaren, CE Pelot, D Fujikawa-Brooks, S Carpenter, PM Hawk, E Kelloff, G Lawson, MJ Kidao, J McCracken, J Albers, CG Ahnen, DJ Turgeon, DK Goldschmid, S Lance, P Hagedorn, CH Gillen, DL Gerner, EW AF Meyskens, Frank L., Jr. McLaren, Christine E. Pelot, Daniel Fujikawa-Brooks, Sharon Carpenter, Philip M. Hawk, Ernest Kelloff, Gary Lawson, Michael J. Kidao, Jayashri McCracken, John Albers, C. Gregory Ahnen, Dennis J. Turgeon, D. Kim Goldschmid, Steven Lance, Peter Hagedorn, Curt H. Gillen, Daniel L. Gerner, Eugene W. TI Difluoromethylornithine Plus Sulindac for the Prevention of Sporadic Colorectal Adenomas: A Randomized Placebo-Controlled, Double-Blind Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID COLON-CANCER; ALPHA-DIFLUOROMETHYLORNITHINE; CHEMOPREVENTION; POLYAMINES; CELECOXIB; ASPIRIN; POLYPS AB Preclinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities, suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas. Three hundred seventy-five patients with history of resected (>= 3 mm) adenomas were randomly assigned to receive oral difluoromethylornithine (DFMO) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months, stratified by use of low-dose aspirin (81 mg) at baseline and clinical site. Follow-up colonoscopy was done 3 years after randomization or off-study. Colorectal adenoma recurrence was compared among the groups with log-binomial regression. Comparing the outcome in patients receiving placebos to those receiving active intervention, (a) the recurrence of one or more adenomas was 41.1% and 12.3% (risk ratio, 0.30; 95% confidence interval, 0.18-0.49; P < 0.001); (b) 8.5% had one or more advanced adenomas, compared with 0.7% of patients (risk ratio, 0.085; 95% confidence interval, 0.011-0.65; P < 0.001); and (c) 17 (13.2%) patients had multiple adenomas (>1) at the final colonoscopy, compared with 1 (0.7%; risk ratio, 0.055; 0.0074-0.41; P < 0.001). Serious adverse events (grade >= 3) occurred in 8.2% of patients in the placebo group, compared with 11% in the active intervention group (P = 0.35). There was no significant difference in the proportion of patients reporting hearing changes from baseline. Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects. C1 [Meyskens, Frank L., Jr.; McLaren, Christine E.; Pelot, Daniel; Fujikawa-Brooks, Sharon; Carpenter, Philip M.; Albers, C. Gregory; Gillen, Daniel L.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA. [Hawk, Ernest; Kelloff, Gary] NCI, Bethesda, MD 20892 USA. [Hagedorn, Curt H.] Univ Kansas, Kansas City, KS USA. [Kidao, Jayashri] Dept Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Lawson, Michael J.] Kaiser Permanente, Sacramento, CA USA. [Ahnen, Dennis J.] Univ Colorado, Denver, CO 80202 USA. [Ahnen, Dennis J.] Denver Dept Veteran Affairs Med Ctr, Denver, CO USA. [Turgeon, D. Kim] Univ Michigan, Ann Arbor, MI 48109 USA. [Goldschmid, Steven; Lance, Peter; Gerner, Eugene W.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [McCracken, John] Loma Linda Univ, Loma Linda, CA 92350 USA. RP Meyskens, FL (reprint author), UCI Canc Ctr, Bldg 44,Route 81,101 City Dr Canc Ctr, Orange, CA 92668 USA. EM flmeyske@uci.edu RI Lance, Peter/I-2196-2014 OI Lance, Peter/0000-0003-2944-1881 FU National Cancer Institute [NO1-CN75019, CA59024, CA88078, CA47396, CA72008, CA95060, CA63640] FX National Cancer Institute contract no. NO1-CN75019 (F. L. Meyskens, Jr. and C. E. McLaren) and grants CA59024 (F. L. Meyskens, Jr.); CA88078 (F. L. Meyskens, Jr. and C. E. McLaren); CA47396, CA72008, and CA95060 (E. W. Gerner); and CA63640 (C. H. Hagedorn). NR 33 TC 241 Z9 242 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2008 VL 1 IS 1 BP 32 EP 38 DI 10.1158/1940-6207.CAPR-08-0042 PG 7 WC Oncology SC Oncology GA 417UQ UT WOS:000264104400007 PM 18841250 ER PT J AU Shen, Q Uray, IP Li, YX Zhang, Y Hill, J Xu, XC Young, MR Gunther, EJ Hilsenbeck, SG Colburn, NH Chodosh, LA Brown, PH AF Shen, Qiang Uray, Ivan P. Li, Yuxin Zhang, Yun Hill, Jamal Xu, Xiao-Chun Young, Matthew R. Gunther, Edward J. Hilsenbeck, Susan G. Colburn, Nancy H. Chodosh, Lewis A. Brown, Powel H. TI Targeting the Activator Protein 1 Transcription Factor for the Prevention of Estrogen Receptor-Negative Mammary Tumors SO CANCER PREVENTION RESEARCH LA English DT Article ID BREAST-CANCER CELLS; C-JUN; AP-1 ACTIVITY; INDUCED TRANSFORMATION; GENE-EXPRESSION; TRANSGENIC MICE; RETINOIC ACID; GROWTH; BLOCKADE; TRANSACTIVATION AB The oncogene erbB2 is overexpressed in 20% to 30% human breast cancers and is most commonly overexpressed in estrogen receptor (ER)-negative breast cancers. Transgenic mice expressing erbB2 develop ER-negative mammary tumors, mimicking human breast carcinogenesis. Previously, we have shown that activator protein 1 (AP-1) regulates proliferation of ER-negative breast cancer cells. We hypothesized that blockade of AP-1 in mouse mammary epithelial cells will suppress ER-negative tumorigenesis induced by erbB2. Trigenic erbB2 mice were generated by crossing a bigenic pUHD-Tam67/MMTV-rtTA mouse to a MMTV-erbB2 mouse. The resulting trigenic mice develop tumors and express a doxy-cycline-inducible c-Jun dominant negative mutant (Tam67) in the mammary glands. In vivo AP-1 blockade by Tam67 expression started delayed mammary tumor formation in MMTV-erbB2 mice by more than 11 weeks. By 52 weeks of age, 100% (18 of 18) of the untreated animals had developed mammary tumors, whereas 56% (9 of 16) of the doxycycline-treated trigenic mice developed tumors. In addition, the tumors that arose in the AP-1-blocked erbB2 mice failed to express Tam67. Twenty-five percent of the doxycycline-treated MMTV-erbB2 mice survived more than 72 weeks of age without developing mammary tumors. Examination of normal-appearing mammary glands from these mice showed that AP-1 blockade by Tam67 also significantly prevents the development of premalignant lesions in these glands. The expression of erbB2 either in normal mammary tissue or in mammary tumors was not altered. Our results show that blocking the AP-1 signaling in mammary cells suppresses erbB2-induced transformation, and show that the AP-1 transcription factor is a critical transducer of erbB2. These results provide a scientific rationale to develop targeted drugs that inhibit AP-1 to prevent the development of ER-negative breast cancer. C1 [Shen, Qiang; Uray, Ivan P.; Li, Yuxin; Zhang, Yun; Hill, Jamal; Hilsenbeck, Susan G.; Brown, Powel H.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Gunther, Edward J.; Chodosh, Lewis A.] Univ Penn, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. [Young, Matthew R.; Colburn, Nancy H.] Natl Canc Inst Frederick, Lab Canc Prevent, Frederick, MD USA. [Xu, Xiao-Chun] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. RP Brown, PH (reprint author), Baylor Coll Med, Lester & Sue Smith Breast Ctr, Dan L Duncan Canc Ctr, 1 Baylor Plaza,MS600, Houston, TX 77030 USA. EM pbrown@breastcenter.tmc.edu OI Shen, Qiang/0000-0002-1491-5434 FU NIH [CA123246] FX Dan L. Duncan Cancer Center at Baylor College of Medicine and NIH R01 grant CA123246 ( P. H. Brown). NR 37 TC 11 Z9 11 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2008 VL 1 IS 1 BP 45 EP 55 DI 10.1158/1940-6207.CAPR-08-0034 PG 11 WC Oncology SC Oncology GA 417UQ UT WOS:000264104400009 PM 19138935 ER PT J AU Yan, J Yang, XP Kim, YS Jetten, AM AF Yan, Jun Yang, Xiao-Ping Kim, Yong-Sik Jetten, Anton M. TI RAP80 responds to DNA damage induced by both ionizing radiation and UV irradiation and is phosphorylated at Ser(205) SO CANCER RESEARCH LA English DT Article ID ATM-DEPENDENT PHOSPHORYLATION; DOUBLE-STRAND BREAKS; BRCA1 BRCT-DOMAIN; H2AX PHOSPHORYLATION; TARGETS BRCA1; PROTEIN; REPAIR; ACTIVATION; CHECKPOINT; INTERACTS AB Receptor-associated protein (RAP80), a nuclear protein containing two ubiquitin-interacting motifs (UIM), was recently found to be associated with breast cancer-1 (BRCA1) and to translocate to ionizing radiation-induced foci (IRIF). In this study, we show that the BRCT mutant of BRCA1, R1699W, which is associated with increased risk of breast cancer, is unable to interact with RAP80. Previously, we showed that ataxia-telangiectasia mutated protein kinase (ATM) can phosphorylate RAP80 in vitro at Ser(205), but whether this site is a target of ATM in whole cells was not established. To address this question, we generated an anti-RAP80Ser205(P) antibody that specifically recognizes RAP80 phosphorylated at Ser(205). Our data show that RAP80 becomes phosphorylated at Ser(205) in cells exposed to ionizing irradiation and that RAP80Ser205(P) translocates to IRIF. We show that this phosphorylation is mediated by ATM and does not require a functional BRCA1. The phosphorylation occurs within 5 minutes after irradiation, long before the translocation of RAP80 to IRIF. In addition, we show that UV irradiation induces translocation of RAP80 to DNA damage foci that colocalize with gamma-H2AX. We further show that this translocation is also dependent on the UIMs of RAP80 and that the UV-induced phosphorylation of RAP80 at Ser(205) is mediated by ATM- and RAD3-related kinase, not ATM. These findings suggest that RAP80 has a more general role in different types of DNA damage responses. C1 [Yan, Jun; Yang, Xiao-Ping; Kim, Yong-Sik; Jetten, Anton M.] NIEHS, Cell Biol Sect, Lab Resp Biol, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Lab Resp Biol, Div Intramural Res,NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS [Z01 ES101586-05] NR 41 TC 14 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2008 VL 68 IS 11 BP 4269 EP 4276 DI 10.1158/0008-5472.CAN-07-5950 PG 8 WC Oncology SC Oncology GA 309TV UT WOS:000256484000031 PM 18519686 ER PT J AU Suzuki, H Morris, JS Li, YN Doll, MA Hein, DW Liu, J Jiao, L Hassan, MM Day, RS Bondy, ML Abbruzzese, JL Li, DH AF Suzuki, Hideo Morris, Jeffrey S. Li, Yanan Doll, Mark A. Hein, David W. Liu, Jun Jiao, Li Hassan, Manal M. Day, Rena S. Bondy, Melissa L. Abbruzzese, James L. Li, Donghui TI Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer SO CARCINOGENESIS LA English DT Article ID ARYLAMINE N-ACETYLTRANSFERASE; HETEROCYCLIC AMINES; CHEMICAL CARCINOGENESIS; METABOLIC-ACTIVATION; SULFOTRANSFERASE 1A1; MOLECULAR-GENETICS; FLUOROGENIC PROBES; COLORECTAL-CANCER; AROMATIC-AMINES; GENOTYPE METHOD AB Aromatic amines, N-nitroso compounds and heterocyclic amines are suspected human pancreatic carcinogens. Cytochrome P450 (CYP) 1A2, N-acetyltransferase (NAT) 1, NAT2 and sulfotransferase (SULT) are enzymes involved in the metabolism of these carcinogens. To test the hypothesis that genetic variations in carcinogen metabolism modify the risk of pancreatic cancer (PC), we investigated the effect of single-nucleotide polymorphisms (SNPs) of the CYP1A2, NAT1, NAT2 and SULT1A1 gene on modification of the risk of PC in a hospital-based study of 755 patients with pancreatic adenocarcinoma and 636 healthy frequency-matched controls. Smoking and dietary mutagen exposure information was collected by personal interviews. Genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism and Taqman methods. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multivariate logistic regression analysis. We observed no significant main effects of any of these genes on the risk of PC. The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men. In contrast, a significant interaction between NAT1 genotype and dietary mutagen intake on modifying the risk of PC were observed among men but not women. The OR (95% CI) of PC was 2.23 (1.33-3.72) and 2.54 (1.51-4.25) for men having the NAT1*10 and a higher intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine and benzo[ a] pyrene, respectively, compared with individuals having no NAT1*10 or a lower intake of these dietary mutagens. These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC. C1 [Suzuki, Hideo; Li, Yanan; Hassan, Manal M.; Abbruzzese, James L.; Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Morris, Jeffrey S.; Liu, Jun] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Bondy, Melissa L.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Jiao, Li] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Doll, Mark A.; Hein, David W.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Doll, Mark A.; Hein, David W.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Day, Rena S.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77025 USA. RP Li, DH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dli@mdanderson.org RI Hein, David/A-9707-2008 FU NCI NIH HHS [R01 CA034627-20, CA034627, CA16672, CA98380, R01 CA034627, R01 CA034627-21, R01 CA034627-22, R01 CA098380, R01 CA098380-01A2, R01 CA098380-02, R01 CA098380-03, R01 CA098380-04, R01 CA098380-05]; NIEHS NIH HHS [P30 ES007784, P30 ES007784-04, P30 ES07784] NR 59 TC 40 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2008 VL 29 IS 6 BP 1184 EP 1191 DI 10.1093/carcin/bgn085 PG 8 WC Oncology SC Oncology GA 322TL UT WOS:000257398100014 PM 18499698 ER PT J AU Kandalaft, LE Zudaire, E Portal-Nunez, S Cuttitta, F Jakowlew, SB AF Kandalaft, Lana E. Zudaire, Enrique Portal-Nunez, Sergio Cuttitta, Frank Jakowlew, Sonia B. TI Differentially expressed nucleolar transforming growth factor-beta 1 target (DENTT) exhibits an inhibitory role on tumorigenesis SO CARCINOGENESIS LA English DT Article ID HUMAN LUNG-CANCER; DNA METHYLATION; GROWTH-FACTOR; CELL-LINES; MICE; PROTEIN AB Differentially expressed nucleolar transforming growth factor-beta 1 target (DENTT), also known as testis-specific protein Y-encoded-like (TSPYL-2) and cell division autoantigen-1, is a member of the testis-specific protein Y-encoded (TSPY)/TSPY-L/SET/nucleosome assembly protein-1 superfamily. DENTT is expressed in various tissues including normal human lung. Here, we investigate the involvement of DENTT in cancer promotion and progression. DENTT messenger RNA (mRNA) and protein levels were shown to be markedly downregulated in human and mouse primary tumors and in human tumor cell lines. Overexpression of DENTT in human lung (A549-DENTT) and breast (MCF-7-DENTT) cancer cells resulted in diminished growth potential in anchorage-dependent growth assays and reduced capacity to form colonies under anchorage-independent culture conditions. The migratory potential of A549-DENTT and MCF-7-DENTT cells was reduced when compared with empty vector control cells. Treating human lung cell lines with demethylating agents increased DENTT expression significantly. DENTT expression pattern paralleled that of transforming growth factor-beta 1 (TGF-beta 1) in normal and malignant tissue and ectopic expression or treatment with TGF-beta 1 in lung cancer cells was followed by increased DENTT mRNA and protein levels. Collectively, our results suggest a role for DENTT as a suppressor of the tumorigenic phenotype. C1 [Kandalaft, Lana E.] Adv Technol Ctr, Natl Canc Inst, Cell & Canc Biol Branch, Gaithersburg, MD 20877 USA. [Zudaire, Enrique; Portal-Nunez, Sergio; Cuttitta, Frank] Adv Technol Ctr, Natl Canc Inst, Natl Canc Inst Angiogenesis Core Facil, Gaithersburg, MD 20877 USA. [Jakowlew, Sonia B.] Natl Canc Inst, Cell & Canc Biol Branch, Rockville, MD 20850 USA. RP Kandalaft, LE (reprint author), Adv Technol Ctr, Natl Canc Inst, Cell & Canc Biol Branch, Gaithersburg, MD 20877 USA. EM kandalal@mail.nih.gov RI Portal-Nunez, Sergio/L-7391-2014; Cuttitta, Frank/B-4758-2016 OI Portal-Nunez, Sergio/0000-0003-0659-1545; FU Intramural NIH HHS NR 21 TC 19 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2008 VL 29 IS 6 BP 1282 EP 1289 DI 10.1093/carcin/bgn087 PG 8 WC Oncology SC Oncology GA 322TL UT WOS:000257398100028 PM 18381359 ER PT J AU Nechaev, S Adelman, K AF Nechaev, Sergei Adelman, Karen TI Promoter-proximal pol II: When stalling speeds things up SO CELL CYCLE LA English DT Article DE RNA polymerase II; transcription elongation; gene regulation; development ID RNA-POLYMERASE-II; HEAT-SHOCK GENES; DROSOPHILA-MELANOGASTER; IN-VIVO; P-TEFB; TRANSCRIPTION ELONGATION; HSP70 PROMOTER; CHROMATIN-STRUCTURE; GAGA FACTOR; ARCHITECTURE AB Expression of genes was long thought to be regulated primarily at the level of RNA polymerase II (Pol II) recruitment to a gene promoter, and the dozen genes that did not fit this paradigm were regarded as exceptions. However, recent analyses of genome-wide Pol II distribution in Drosophila and mammalian systems have indicated that a large number of genes might be regulated at a step subsequent to Pol II recruitment, during early transcription elongation. At these genes, Pol II begins transcription but stalls after synthesizing a short RNA, and it is the release of this engaged Pol II from the promoter-proximal region that is rate limiting for transcription. Notably, promoter-proximal Pol II stalling is prevalent at genes involved in development and response to stimuli, suggesting that Pol II stalling during early elongation plays important roles in rapid and precise control of gene expression. Here we briefly summarize the current data on promoter-proximal Pol II stalling and discuss implications of this newly appreciated regulatory strategy. C1 [Nechaev, Sergei; Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Nechaev, S (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM nechaevs@niehs.nih.gov; adelmank@niehs.nih.gov FU Intramural NIH HHS NR 47 TC 55 Z9 57 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2008 VL 7 IS 11 BP 1539 EP 1544 DI 10.4161/cc.7.11.6006 PG 6 WC Cell Biology SC Cell Biology GA 312US UT WOS:000256697100007 PM 18469524 ER PT J AU Belkaid, Y AF Belkaid, Yasmine TI Paradoxical roles of Foxp3(+) T cells during infection: From regulators to regulators SO CELL HOST & MICROBE LA English DT Editorial Material ID PLASMACYTOID DENDRITIC CELLS; AUTOIMMUNITY AB T cells expressing the transcription factor Foxp3 have been shown to limit immune responses against microbes. In a recent issue of Science, Lund et al. support the idea that these cells can also coordinate the early entrance of innate cells at the effector site and therefore positively contribute to protective immunity. C1 NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM ybelkaid@mail.nih.gov FU Intramural NIH HHS [Z01 AI000955-04] NR 12 TC 3 Z9 3 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD JUN PY 2008 VL 3 IS 6 BP 341 EP 343 DI 10.1016/j.chom.2008.05.011 PG 3 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 316GE UT WOS:000256936600003 PM 18541209 ER PT J AU Ikonomou, L Geras-Raaka, E Raaka, BM Gershengorn, MC AF Ikonomou, L. Geras-Raaka, E. Raaka, B. M. Gershengorn, M. C. TI beta-catenin signalling in mesenchymal islet-derived precursor cells SO CELL PROLIFERATION LA English DT Article ID SUPPRESSES OSTEOGENIC DIFFERENTIATION; INTEGRIN-LINKED KINASE; IN-VITRO; STEM-CELLS; CYCLIN D1; TRANSCRIPTIONAL ACTIVITY; PROMOTES PROLIFERATION; STROMAL CELLS; COLON-CANCER; E-CADHERIN AB Objectives: Previously, we characterized human islet-derived precursor cells (hIPCs) as mesenchymal stem cells that migrate out from islets in vitro and can differentiate into functional islet-like structures following proliferative expansion. Here, we investigate the role of beta-catenin signalling in derivation and proliferation of hIPCs. Materials and methods: Localization of beta-catenin was performed using confocal microscopy. Expression levels of beta-catenin target genes were measured by quantitative real-time polymerase chain reaction. Loss-of-function studies were performed using specific short interfering RNAs. Results: Immunostaining of islet outgrowths revealed translocation of beta-catenin from plasma membranes in intact islets to the nucleus in cells migrating out. There were no nuclear beta-catenin-positive cells in intact islets whereas between 35% and 70% of cells in established hIPC cultures exhibited nuclear beta-catenin. Transcripts for beta-catenin target genes were increased in hIPCs compared to those in islets. beta-Catenin translocated to the cell membrane when hIPCs formed epithelial cell clusters. In proliferating hIPCs, there was a strong correlation between markers of proliferation and nuclear beta-catenin. Treatment of hIPCs with the glycogen synthase kinase-3 beta inhibitor (2'Z,3'E)-6-Bromoindirubin-3'-oxime increased intracellular beta-catenin but reduced nuclear beta-catenin, and was associated with reduced cell proliferation. Finally, knockdown of beta-catenin decreased beta-catenin target gene expression and hIPC proliferation. Conclusions: These results support a functional role for beta-catenin during proliferation of hIPCs and suggest that activated beta-catenin signalling may also be important during hIPC derivation from islets. C1 [Ikonomou, L.; Geras-Raaka, E.; Raaka, B. M.; Gershengorn, M. C.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, 50 S Dr,Rm 4134, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Ikonomou, Laertis/D-4579-2009 OI Ikonomou, Laertis/0000-0003-0993-6713 FU Intramural NIH HHS [Z01 DK011007-06, Z01 DK047046-01] NR 62 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD JUN PY 2008 VL 41 IS 3 BP 474 EP 491 DI 10.1111/j.1365-2184.2008.00527.x PG 18 WC Cell Biology SC Cell Biology GA 301SV UT WOS:000255916800007 PM 18422699 ER PT J AU Stangl, S Gross, C Pockley, AG Asea, AA Multhoff, G AF Stangl, Stefan Gross, Catharina Pockley, Alan G. Asea, Alexzander A. Multhoff, Gabriele TI Influence of Hsp70 and HLA-E on the killing of leukemic blasts by cytokine/Hsp70 peptide-activated human natural killer (NK) cells SO CELL STRESS & CHAPERONES LA English DT Article DE human; natural killer cells; cell surface molecules; cytotoxicity; tumor immunity ID HEAT-SHOCK-PROTEIN; SEVERE COMBINED IMMUNODEFICIENCY; CYTOLYTIC ACTIVITY; TUMOR-CELLS; SURFACE; RECEPTORS; BIOLOGY; MICE; RECOGNITION; MOLECULES AB This study compared the effects of the human 70-kDa stress protein (Hsp70) peptide, TKDNNLLGRFELSG (TKD), proinflammatory cytokines, or a combination of both on the repertoire of receptors expressed by human natural killer (NK) cells and their capacity to kill human CX colon carcinoma cells, K562 erythroleukemic cells, and leukemic blasts from two patients with acute myelogenous leukemia. Low-dose interleukin (IL) 2/IL-15 and TKD increase the expression density of activatory (NKG2D, NKp30, NKp44, NKp46, CD94/NKG2C) and inhibitory (CD94/NKG2A) receptors on NK cells. Concomitantly, IL-2/TKD treatment enhances the cytotoxicity of NK cells (as reflected by their secretion of granzyme B) against Hsp70 membrane-positive and human leukocyte antigen (HLA)-E membrane-negative (Hsp70(+)/HLA-E-) CX+ and K562 cells. However, it had no effect on the responsiveness to Hsp70(-)/HLA-E- CX- cells over that induced by IL-2 alone. The cytotoxicity of IL-2/TKD-activated, purified NK cells and peripheral blood mononuclear cells against Hsp70(+)/HLA-E+ leukemic blasts was weaker than that against Hsp70(+)/HLA-E- K562 cells. Hsp70-blocking and HLA-E transfection experiments confirmed membrane-bound Hsp70 as being a recognition/activatory ligand for NK cells, as cytotoxicity was reduced by the presence of the anti-Hsp70 monoclonal antibody cmHsp70.2 and by inhibiting Hsp70 synthesis using short interference ribonucleic acid. HLA-E was confirmed as an inhibitory ligand, as the extent of NK cell-mediated lysis of K562 cell populations that had been transfected with HLA-ER or HLA-EG alleles was dependent on the proportion of HLA-E-expressing cells. These findings indicate that Hsp70 (as an activatory molecule) and HLA-E (as an inhibitory ligand) expression influence the susceptibility of leukemic cells to the cytolytic activities of cytokine/TKD-activated NK cells. C1 [Stangl, Stefan; Pockley, Alan G.; Multhoff, Gabriele] Tech Univ Munich, Dept Radiotherapy & Radiooncol, Klinikum Rechts Isar, D-81675 Munich, Germany. [Gross, Catharina] NIAID, NIH, Rockville, MD USA. [Pockley, Alan G.] Univ Sheffield, Sch Med & Biomed Sci, Sheffield, S Yorkshire, England. [Asea, Alexzander A.] Texas A&M Univ, Coll Med, Syst Hlth Sci Ctr, Scott & White Clin, Temple, TX 76508 USA. [Multhoff, Gabriele] German Res Ctr Environm & Hlth GmbH, Inst Pathol, Helmholtz Ctr Munich, KKG Innate Immun Tumor Biol, Munich, Germany. RP Multhoff, G (reprint author), Tech Univ Munich, Dept Radiotherapy & Radiooncol, Klinikum Rechts Isar, Ismaningerstr 22, D-81675 Munich, Germany. EM gabriele.multhoff@lrz.tu-muenchen.de RI Asea, Alexzander/I-4112-2013; OI Asea, Alexzander/0000-0003-3592-3481; Pockley, Alan/0000-0001-9593-6431 NR 29 TC 14 Z9 17 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD JUN PY 2008 VL 13 IS 2 BP 221 EP 230 DI 10.1007/s12192-007-0008-y PG 10 WC Cell Biology SC Cell Biology GA 294HV UT WOS:000255398000009 PM 18759005 ER PT J AU Crawley, JN AF Crawley, J. N. TI Galanin impairs cognitive abilities in rodents: relevance to Alzheimer's Disease SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Alzheimer's; fear conditioning; learning and memory; Morris water maze; receptor knockout mice; social transmission of food preference; transgenic mice ID OVEREXPRESSING TRANSGENIC MICE; RAT VENTRAL HIPPOCAMPUS; NONMATCHING-TO-SAMPLE; ELEVATED PLUS-MAZE; SPONTANEOUS-ALTERNATION PERFORMANCE; VITRO AUTORADIOGRAPHIC ANALYSIS; CHOLINERGIC BASAL FOREBRAIN; AMYLOID PRECURSOR PROTEIN; RELEASE IN-VIVO; ACETYLCHOLINE-RELEASE AB The neuropeptide galanin and its receptors are localized in brain pathways mediating learning and memory. Central microinjection of galanin impairs performance of a variety of cognitive tasks in rats. Transgenic mice overexpressing galanin display deficits in some learning and memory tests. The inhibitory role of galanin in cognitive processes, taken together with the overexpression of galanin in Alzheimer's disease, suggests that galanin antagonists may offer a novel therapeutic approach to treat memory loss in Alzheimer's patients. C1 NIMH, Lab Behav Neurosci, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Crawley, JN (reprint author), NIMH, Lab Behav Neurosci, Porter Neurosci Res Ctr, Bldg 35,Room 1C-903,Mail Code 3730, Bethesda, MD 20892 USA. EM crawleyj@intra.nimh.nih.gov FU Intramural NIH HHS [Z01 MH002177-22] NR 78 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUN PY 2008 VL 65 IS 12 BP 1836 EP 1841 DI 10.1007/s00018-008-8158-3 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 316CV UT WOS:000256927400007 PM 18500642 ER PT J AU Lu, L Fang, YX Wang, X AF Lu, Lin Fang, Yuxia Wang, Xi TI Drug abuse in China: Past, present and future SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE drug abuse; history; drug trafficking; Chinese medicine; methadone maintenance treatment; harm reduction ID SUBSTANCE-ABUSE; HIV-INFECTION; ACUPUNCTURE; USERS; ADDICTION; DETOXIFICATION; TRANSMISSION; ATTITUDES; PATTERNS; PROGRAM AB Following British importation of opium to China in 1760s, the use and production of the drug in China increased dramatically. This situation was aggravated after the failure of Opium Wars that occurred between the United Kingdom and the Qing Empire in China with the aim of forcing China to import British Opium; this war made China open the door to a free flowing opium trade, with disastrous social and public health consequences. The subsequent rise of the new China created drug-free atmosphere by strict legislation and punishment, in which drug use greatly decreased. However, in the context of governmental reform and the open-door policies of the 1980s, drug abuse has re-emerged as a major public health problem. Today, drug abuse is highly linked to the spread of HIV/AIDS and to drug-related crimes in China. To combat the severe drug problem facing the nation, the Chinese government has adopted the Methadone Maintenance Treatment program, a multi-faceted therapeutic approach that aims to reduce the health and social problem induced by drug epidemics. In addition, traditional Chinese medicine, including herbal therapy and acupuncture, both found to be effective in the prevention of relapse and causes few side effects, making them useful for the treatment of opiate addiction. With continuous application of these therapies and managements that have been proved to be effective in harm reduction in the western countries, we believe that drug abuse and its related problems in China will be brought under control. C1 [Lu, Lin; Wang, Xi] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. [Fang, Yuxia] Natl Inst Drug Abuse, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn NR 52 TC 54 Z9 61 U1 4 U2 44 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 2008 VL 28 IS 4 BP 479 EP 490 DI 10.1007/s10571-007-9225-2 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 296IC UT WOS:000255535700002 PM 17990098 ER PT J AU Jong, A Wu, CH Shackleford, GM Kwon-Chung, KJ Chang, YC Chen, HM Ouyang, Y Huang, SH AF Jong, Ambrose Wu, Chun-Hua Shackleford, Gregory M. Kwon-Chung, Kyung J. Chang, Yun C. Chen, Han-Min Ouyang, Yannan Huang, Sheng-He TI Involvement of human CD44 during Cryptococcus neoformans infection of brain microvascular endothelial cells SO CELLULAR MICROBIOLOGY LA English DT Article ID CAPSULE-ASSOCIATED GENE; SIGNAL-TRANSDUCTION; ACTIN CYTOSKELETON; LIPID RAFTS; ASSOCIATION; VIRULENCE; INVASION; RECEPTOR; SHIGELLA; BARRIER AB Pathogenic yeast Cryptococcus neoformans causes devastating cryptococcal meningoencephalitis. Our previous studies demonstrated that C. neoformans hyaluronic acid was required for invasion into human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. In this report, we demonstrate that C. neoformans hyaluronic acid interacts with CD44 on HBMEC. Our results suggest that HBMEC CD44 is a primary receptor during C. neoformans infection, based on the following observations. First, anti-CD44 neutralizing antibody treatment was able to significantly reduce C. neoformans association with HBMEC. Second, C. neoformans association was considerably impaired using either CD44-knock-down HBMEC or C. neoformans hyaluronic acid-deficient strains. Third, overexpression of CD44 in HBMEC increased their association activity towards C. neoformans. Fourth, confocal microscopic images showed that CD44 was enriched at and around the C. neoformans association sites. Fifth, upon C. neoformans and HBMEC engagement, a subpopulation of CD44 and actin translocated to the host membrane rafts. Our results highlight the interactions between C. neoformans hyaluronic acid and host CD44 and the dynamic results of these interactions, which may represent events during the adhesion and entry of C. neoformans at HBMEC membrane rafts. C1 [Jong, Ambrose; Wu, Chun-Hua; Shackleford, Gregory M.; Ouyang, Yannan] Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med,Div Hematol Oncol, Dept Pediat,Saban Res Inst, Los Angeles, CA 90027 USA. [Huang, Sheng-He] Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med,Div Infect Dis, Dept Pediat,Saban Res Inst, Los Angeles, CA 90027 USA. [Kwon-Chung, Kyung J.; Chang, Yun C.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Chen, Han-Min] Fu Jen Catholic Univ, Dept Life Sci, Taipei, Taiwan. RP Jong, A (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med,Div Hematol Oncol, Dept Pediat,Saban Res Inst, Los Angeles, CA 90027 USA. EM ajong@chla.usc.edu FU Intramural NIH HHS; NIAID NIH HHS [R01-AI40635]; NINDS NIH HHS [R01-NS047599] NR 46 TC 48 Z9 56 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JUN PY 2008 VL 10 IS 6 BP 1313 EP 1326 DI 10.1111/j.1462-5822.2008.01128.x PG 14 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 300JL UT WOS:000255820000009 PM 18248627 ER PT J AU Wickliffe, KE Leppla, SH Moayeri, M AF Wickliffe, Katherine E. Leppla, Stephen H. Moayeri, Mahtab TI Killing of macrophages by anthrax lethal toxin: involvement of the N-end rule pathway SO CELLULAR MICROBIOLOGY LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; BACILLUS-ANTHRACIS; APOPTOSIS PROTEIN; PROTEOLYTIC PATHWAY; PROTEASOME ACTIVITY; PROTECTIVE ANTIGEN; KINASE-KINASE; IAP PROTEINS; TNF-ALPHA; IN-VITRO AB Macrophages from certain inbred mouse strains are rapidly killed (< 90 min) by anthrax lethal toxin (LT). LT cleaves cytoplasmic MEK proteins at 20 min and induces caspase-1 activation in sensitive macrophages at 50-60 min, but the mechanism of LT-induced death is unknown. Proteasome inhibitors block LT-mediated caspase-1 activation and can protect against cell death, indicating that the degradation of at least one cellular protein is required for LT-mediated cell death. Proteins can be degraded by the proteasome via the N-end rule, in which a protein's stability is determined by its N-terminal residue. Using amino acid derivatives that act as inhibitors of this pathway, we show that the N-end rule is required for LT-mediated caspase-1 activation and cell death. We also found that bestatin methyl ester, an aminopeptidase inhibitor protects against LT in vitro and in vivo and that the different inhibitors of the protein degradation pathway act synergistically in protecting against LT. We identify c-IAP1, a mammalian member of the inhibitor of apoptosis protein (IAP) family, as a novel N-end rule substrate degraded in macrophages treated with LT. We also show that LT-induced c-IAP1 degradation is independent of the IAP-antagonizing proteins Smac/DIABLO and Omi/HtrA2, but dependent on caspases. C1 [Wickliffe, Katherine E.; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Moayeri, M (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mmoayeri@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000929-05] NR 60 TC 24 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD JUN PY 2008 VL 10 IS 6 BP 1352 EP 1362 DI 10.1111/j.1462-5822.2008.01131.x PG 11 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 300JL UT WOS:000255820000012 PM 18266992 ER PT J AU Rogers, ME Hajmova, M Joshi, MB Sadlova, J Dwyer, DM Volf, P Bates, PA AF Rogers, Matthew E. Hajmova, Martina Joshi, Manju B. Sadlova, Jovana Dwyer, Dennis M. Volf, Petr Bates, Paul A. TI Leishmania chitinase facilitates colonization of sand fly vectors and enhances transmission to mice SO CELLULAR MICROBIOLOGY LA English DT Article ID LUTZOMYIA-LONGIPALPIS; PERITROPHIC MATRIX; DEVELOPMENTAL BIOLOGY; PHLEBOTOMUS-PAPATASI; INFECTIVE STAGE; PROMASTIGOTES; FLIES; PSYCHODIDAE; MECHANISM; SANDFLIES AB Chitinases of trypanosomatid parasites have been proposed to fulfil various roles in their blood-feeding arthropod vectors but so far none have been directly tested using a molecular approach. We characterized the ability of Leishmania mexicana episomally transfected with LmexCht1 (the L. mexicana chitinase gene) to survive and grow within the permissive sand fly vector, Lutzomyia longipalpis. Compared with control plasmid transfectants, the overexpression of chitinase was found to increase the average number of parasites per sand fly and accelerate the escape of parasites from the peritrophic matrix-enclosed blood meal as revealed by earlier arrival at the stomodeal valve. Such flies also exhibited increased damage to the structure of the stomodeal valve, which may facilitate transmission by regurgitation. When exposed individually to BALB/c mice, those flies with chitinase-overexpressing parasites spent on average 2.4-2.5 times longer in contact with their host during feeding, compared with flies with control infections. Furthermore, the lesions that resulted from these single fly bite infections were both significantly larger and with higher final parasite burdens than controls. These data show that chitinase is a multifunctional virulence factor for L. mexicana which assists its survival in Lu. longipalpis. Specifically, this enzyme enables the parasites to colonize the anterior midgut of the sand fly more quickly, modify the sand fly stomodeal valve and affect its blood feeding, all of which combine to enhance transmission. C1 [Rogers, Matthew E.; Bates, Paul A.] Univ Liverpool Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Hajmova, Martina; Sadlova, Jovana; Volf, Petr] Charles Univ Prague, Fac Sci, Dept Parasitol, CR-12844 Prague 2, Czech Republic. [Joshi, Manju B.; Dwyer, Dennis M.] NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Rogers, ME (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Immunol, Norfolk Pl, London W2 1PG, England. EM matthew.rogers@imperial.ac.uk RI Sadlova, Jovana/C-1327-2012; Volf, Petr/C-4300-2012; OI Sadlova, Jovana/0000-0002-0432-2707; Volf, Petr/0000-0003-1790-1123; Bates, Paul/0000-0001-6861-5421 FU Intramural NIH HHS; Wellcome Trust [064945, 078937, WT078223MA] NR 35 TC 33 Z9 33 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JUN PY 2008 VL 10 IS 6 BP 1363 EP 1372 DI 10.1111/j.1462-5822.2008.01132.x PG 10 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 300JL UT WOS:000255820000013 PM 18284631 ER PT J AU Duque, J Mazzocchio, R Stefan, K Hummel, F Olivier, E Cohen, LG AF Duque, J. Mazzocchio, R. Stefan, K. Hummel, F. Olivier, E. Cohen, Leonardo G. TI Memory formation in the motor cortex ipsilateral to a training hand SO CEREBRAL CORTEX LA English DT Article DE inhibition; ipsilateral M1; motor learning; plasticity; TMS; training ID TRANSCRANIAL MAGNETIC STIMULATION; USE-DEPENDENT PLASTICITY; PREMOTOR CORTEX; DORSAL PREMOTOR; INTERHEMISPHERIC INHIBITION; SUPPLEMENTARY MOTOR; CORTICOSPINAL EXCITABILITY; MOVEMENT REPRESENTATIONS; MACAQUE MONKEYS; CHRONIC STROKE AB Cortical reorganization within the primary motor cortex (M1) contralateral to a practicing hand has been extensively investigated. The extent to which the ipsilateral M1 participates in these plastic changes is not known. Here, we evaluated the influence of unilateral hand practice on the organization of the M1 ipsilateral and contralateral to the practicing hand in healthy human subjects. Index finger movements elicited by single-pulse transcranial magnetic stimulation (TMS) delivered to each M1 were evaluated before and after practice of unilateral voluntary index finger abduction motions. Practice increased the proportion and acceleration of TMS-evoked movements in the trained direction and the amplitude of motor-evoked potentials (MEPs) in the abduction agonist first dorsal interosseous (FDI) muscle in the practicing hand and decreased the proportion and acceleration of TMS-evoked abduction movements and MEP amplitudes in the abduction agonist FDI in the opposite resting hand. Our findings indicate that unilateral hand practice specifically weakened the representation of the practiced movement in the ipsilateral M1 to an extent proportional to the strengthening effect in the contralateral M1, a result that varied with the practicing hand's position. These results suggest a more prominent involvement of interacting bilateral motor networks in motor memory formation and probably acquisition of unimanual motor skills than previously thought. C1 [Duque, J.; Mazzocchio, R.; Stefan, K.; Hummel, F.; Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, Stroke Neurorehabil Clin, Natl Inst Hlth, Bethesda, MD 20817 USA. [Duque, J.; Olivier, E.] Catholic Univ Louvain, Neurophysiol Lab, B-1200 Brussels, Belgium. [Mazzocchio, R.] Univ Siena, Dipartimento Sci Neurol & Comportamento, Sez Neurofisiol Clin, I-53100 Siena, Italy. [Hummel, F.] Univ Med Ctr Hamburg Eppendorf, Cort Physiol Res Grp, Dept Neurol, D-20246 Hamburg, Germany. RP Cohen, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, Stroke Neurorehabil Clin, Natl Inst Hlth, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Mazzocchio, Riccardo/H-4223-2012 OI Mazzocchio, Riccardo/0000-0002-0628-2868 FU Intramural NIH HHS NR 74 TC 32 Z9 32 U1 0 U2 2 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 JUN PY 2008 VL 18 IS 6 BP 1395 EP 1406 DI 10.1093/cercor/bhm173 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 302RY UT WOS:000255988200016 PM 17928331 ER PT J AU Rong, YS AF Rong, Yikang S. TI Telomere capping in Drosophila: dealing with chromosome ends that most resemble DNA breaks SO CHROMOSOMA LA English DT Review ID ATAXIA-TELANGIECTASIA; PROTEIN COMPLEX; MULTIPLE PATHWAYS; BUDDING YEAST; ATM; MAINTENANCE; MELANOGASTER; CHECKPOINT; PROTECTION; FUSIONS AB Telomere caps prevent chromosome ends from being recognized as DNA double-strand breaks (DSBs). Unlike most organisms studied, the telomere-capping function of Drosophila does not require a specific sequence. Without this sequence component, Drosophila telomeres most resemble DNA breaks and, thus, represent a simpler system for the study of telomere capping. I review recent progress in Drosophila telomere studies, and challenge the notion that Drosophila may not be a relevant model for the study of telomere maintenance. C1 NCI, NIH, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. RP Rong, YS (reprint author), NCI, NIH, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov RI rong, yikang/G-6179-2011 FU Intramural NIH HHS NR 54 TC 31 Z9 33 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD JUN PY 2008 VL 117 IS 3 BP 235 EP 242 DI 10.1007/s00412-007-0144-2 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 297LC UT WOS:000255617200002 PM 18193446 ER PT J AU Omland, KS Brys, A Lansky, D Clement, K Lynn, F AF Omland, Kristian S. Brys, April Lansky, David Clement, Kristin Lynn, Freyja CA Participating Labs TI Interlaboratory comparison of results of an anthrax lethal toxin neutralization assay for assessment of functional antibodies in multiple species SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; INTRANASAL CHALLENGE; INHALATION ANTHRAX; IMMUNOGLOBULIN-G; VACCINE; IMMUNOGENICITY; CORRELATE; IMMUNITY AB The anthrax lethal toxin neutralization assay (TNA) will likely be used to correlate the protection offered by new anthrax vaccines in animal models to the immunogenicity that will be provided in humans. TNA data are being generated in several different laboratories to measure the immune responses in rabbits, nonhuman primates, and humans. In order to compare data among species and laboratories, a collaborative study was conducted in which 108 samples from the three species were analyzed in seven independent laboratories. Six of the seven laboratories had participated in an interlaboratory technology transfer of the TNA. Analysis of the titration curves generated by samples from each species indicated that the behaviors of the samples from all species were similar; the upper and lower asymptotes and the slopes of the curves were less than 30% divergent from those for human reference material. Dilutional linearity was consistent among samples from each species, with spike to effective dilution at 50% inhibition (ED 50) slopes of less than 1.2 for all species. Agreement among the laboratories with consensus values was within 10% of the ED50s for all samples and within 7.5% of the quotients of the test sample ED50 and the reference standard ED50 (NF50s) for all samples. The relative standard deviations obtained when data from all laboratories and for all species were combined were 45% for the ED50s and 35% for the NF50s. These precision data suggest that the NF50 readout may normalize the values generated by different laboratories. This study demonstrates that the TNA is a panspecies assay that can be performed in several different laboratories with a high degree of quantitative agreement and precision. C1 [Lynn, Freyja] NIAID, DMID, OBRA, Bethesda, MD 20892 USA. [Omland, Kristian S.; Lansky, David] Precis Bioassay, Burlington, VT USA. [Brys, April] Battelle Eastern Sci & Technol Ctr, Aberdeen, MD USA. [Clement, Kristin] Battelle Biomed Res Ctr, W Jefferson, OH USA. RP Lynn, F (reprint author), NIAID, DMID, OBRA, 6610 Rockledge Dr,Room 5064, Bethesda, MD 20892 USA. EM lynnf@niaid.nih.gov FU National Institutes of Health [N01-AI-30061, N01-AI-05413] FX We acknowledge Emily Kough, Laureen Little, Robert Kohberger, and Carrie Wager for helpful discussions on study design and analysis. The work performed at Battelle Biomedical Research Center and Battelle Eastern Science and Technology Center was supported under National Institutes of Health contract N01-AI-30061. The work performed at VaxGen was supported under National Institutes of Health contract N01-AI-30053. The worked performed at Precision Bioassays was supported under National Institutes of Health contract N01-AI-05413. The members of the participating laboratories were Nathan T. Huber, Addie G. Newman, Robert K. Adkins, and Jeffery L. Senft, Battelle Biomedical Research Center, West Jefferson, OH; Brandi Dorsey, Rebecca Limmer, and Bobbi Horne, Battelle Eastern Science and Technology Center, Aberdeen MD; Leslie Wagner, Anita Verma, Miriam Ngundi, Bruce D. Meade, and Drusilla L. Burns, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD; Conrad P. Quinn and Han Li, Centers for Disease Control and Prevention, Atlanta, GA; Louise Simon and Mark Lyons, Emergent BioSolutions, Lansing MI; Eric Peng, VaxGen Inc., Brisbane, CA; and J. Edward Brown, David G. Pennock, and Wendy Johnson, USAMRIID, Fort Detrick, MD. NR 27 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2008 VL 15 IS 6 BP 946 EP 953 DI 10.1128/CVI.00003-08 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 340TD UT WOS:000258667000007 PM 18417668 ER PT J AU Goldstein, DS Eldadah, B Sharabi, Y Axelrod, FB AF Goldstein, David S. Eldadah, Basil Sharabi, Yehonatan Axelrod, Felicia B. TI Cardiac sympathetic hypo-innervation in familial dysautonomia SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE familial dysautonomia; fluorodopamine; sympathetic nervous system; positron emission tomography; norepinephrine ID DOPAMINE-BETA-HYDROXYLASE; PARKINSONS-DISEASE; AUTONOMIC FAILURE; 6-FLUORODOPAMINE; DYSFUNCTION; HEART AB Objective Familial dysautonomia (FD) involves incomplete development of the sympathetic nervous system. Whether such loss extends to sympathetic innervation of the heart has been unknown. This study used 6-[F-18]fluorodopamine neuroimaging to assess cardiac sympathetic innervation and function in FD. Methods Six adult FD patients underwent thoracic PET scanning for 30 minutes after i.v. 6-[F-18]fluorodopamine injection, as did healthy volunteers without (N = 21) or with (N = 10) pre-treatment by desipramine, which interferes with neuronal uptake and thereby simulates effects of noradrenergic denervation. Effective rate constants for uptake and loss were calculated using a single compartment pharmacokinetic model. Results FD patients had decreased uptake and accelerated loss of 6-[F-18]fluorodopamine-derived radioactivity in the interventricular myocardial septum (P = 0.009, P = 0.05) and ventricular free wall (P = 0.007, P < 0.001), compared to untreated controls. Desipramine-treated subjects had decreased uptake but normal loss of 6-[F-18]fluorodopamine-derived radioactivity. Conclusions FD involves cardiac noradrenergic hypo-innervation. Since accelerated loss of 6-[F-18]fluorodopamine-derived radioactivity cannot be explained by decreased neuronal uptake alone, FD may also involve augmented NE loss from extant terminals. C1 [Goldstein, David S.; Eldadah, Basil; Sharabi, Yehonatan] NINDS, Clin Neurocardial Sect, NIH, Bethesda, MD 20892 USA. [Axelrod, Felicia B.] NYU, Sch Med, New York, NY USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardial Sect, NIH, 10 Ctr Dr,MSC-1620 Bldg 10 Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS [Z01 NS003033-01, Z99 NS999999, Z01 NS003034-01, ] NR 24 TC 9 Z9 9 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD JUN PY 2008 VL 18 IS 3 BP 115 EP 119 DI 10.1007/s10286-008-0464-1 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 308YQ UT WOS:000256427200001 PM 18498023 ER PT J AU Hamm, JT Wilson, JW Rastogi, P Lembersky, BC Tseng, GC Song, YK Kim, W Robidoux, A Raymond, JM Kardinal, CG Shalaby, IA Ansari, R Paik, S Geyer, CE Wolmark, N AF Hamm, John T. Wilson, John W. Rastogi, Priya Lembersky, Barry C. Tseng, George C. Song, Young K. Kim, Wanseop Robidoux, Andre Raymond, Jane M. Kardinal, Carl G. Shalaby, Ibrahim A. Ansari, Rafat Paik, Soonmyung Geyer, Charles E. Wolmark, Norman TI Gemcitabine/epirubicin/paclitaxel as neoadjuvant chemotherapy in locally advanced breast cancer: A phase II trial of the NSABP foundation research group SO CLINICAL BREAST CANCER LA English DT Article DE desquamation; diagonal linear discriminant analysis; gene-expression profiling; myalgia; preoperative chemotherapy ID SURGICAL ADJUVANT BREAST; PROJECT PROTOCOL B-27; PREOPERATIVE CHEMOTHERAPY; INDUCTION CHEMOTHERAPY; CONSERVATIVE TREATMENT; 1ST-LINE CHEMOTHERAPY; MULTIMODAL TREATMENT; RADIATION-THERAPY; TUMOR RESPONSE; 3 CM AB Background: This phase II protocol of neoadjuvant chemotherapy with gemcitabine/eprubicin/paclitaxel (GET) was designed to determine the pathologic complete response (pCR) rate in the breast, clinical response rate, disease-free survival, and overall survival at 2 years as well as toxicity in patients with locally advanced breast cancer. This trial also evaluated the feasibility of tissue collection for gene-expression profiling. Patients and Methods: Seventy-six women with stage IIB, IIIA, and IIIB breast cancer were entered into this trial. Patients received a maximum of 6 cycles of neoadjuvant GET chemotherapy every 21 days (gemcitabine 1000 mg/m(2) intravenously [I.V.] on days 1 and 4, epirubicin 90 mg/m(2) I.V bolus on day 1, and paclitaxel 175 mg/m(2) I.V on day 1). After chemotherapy, patients underwent surgery and were assessed for pathologic response. Results: The pCR rate among the 74 patients evaluable for efficacy was 23% (95% CI, 14%-34.2%). Adverse events among the 76 patients evaluable for toxicity included anemia requiring transfusion (14.5%), infection with grade 3/4 neutropenia (10.5%), febrile neutropenia (7.9%), and platelet transfusion (6.6%). Infectious complications occurred in 24 patients (31.6%), of whom 18.4% were in the setting of neutropenia. High-quality RNA and successful probe synthesis were obtained from all pretreatment core biopsy specimens that contained tumor cells (n = 66; 88%). Conclusion: Neoadjuvant GET chemotherapy is an active regimen but with substantial toxicity. Tissue collection for gene-expression profiling is feasible in a multi-institutional setting. C1 [Hamm, John T.; Wilson, John W.; Rastogi, Priya; Lembersky, Barry C.; Tseng, George C.; Song, Young K.; Kim, Wanseop; Robidoux, Andre; Raymond, Jane M.; Kardinal, Carl G.; Shalaby, Ibrahim A.; Ansari, Rafat; Paik, Soonmyung; Geyer, Charles E.; Wolmark, Norman] Univ Pittsburgh, Magee Womens Hosp, Inst Canc, NSABP,Operat Off, Pittsburgh, PA 15213 USA. [Hamm, John T.; Wilson, John W.; Rastogi, Priya; Lembersky, Barry C.; Tseng, George C.; Song, Young K.; Kim, Wanseop; Robidoux, Andre; Raymond, Jane M.; Kardinal, Carl G.; Shalaby, Ibrahim A.; Ansari, Rafat; Paik, Soonmyung; Geyer, Charles E.; Wolmark, Norman] Ctr Biostat, Pittsburgh, PA USA. [Hamm, John T.] Norton Healthcare Inc, Louisville, KY USA. [Wilson, John W.; Tseng, George C.] Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Dept Biostat, Pittsburgh, PA 15213 USA. [Song, Young K.; Kim, Wanseop; Paik, Soonmyung] NSABP Fdn Inc, Div Pathol, Philadelphia, PA USA. [Robidoux, Andre] CHU Montreal, Quebec City, PQ, Canada. [Raymond, Jane M.; Geyer, Charles E.; Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Kardinal, Carl G.] Alton Ochsner, Community Clin Oncol Program, New Orleans, LA USA. [Shalaby, Ibrahim A.] Joe Arrington Canc Res & Treatment Ctr, Lubbock, TX USA. [Ansari, Rafat] No Indiana Canc Res Consortium, South Bend, IN USA. RP Rastogi, P (reprint author), Univ Pittsburgh, Magee Womens Hosp, Inst Canc, NSABP,Operat Off, 300 Halket St,Rm 3524, Pittsburgh, PA 15213 USA. EM rastogi@nsabp.pitt.edu NR 31 TC 6 Z9 7 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2008 VL 8 IS 3 BP 257 EP 263 DI 10.3816/CBC.2008.n.029 PG 7 WC Oncology SC Oncology GA 315XZ UT WOS:000256914800007 PM 18650156 ER PT J AU Wapnir, IL Aebi, S Geyer, CE Zahrieh, D Gelber, RD Anderson, SJ Robidoux, A Bernhard, J Maibach, R Castiglione-Gertsch, M Coates, AS Piccart, MJ Clemons, MJ Costantino, JP Wolmark, N AF Wapnir, Irene L. Aebi, Stefan Geyer, Charles E. Zahrieh, David Gelber, Richard D. Anderson, Stewart J. Robidoux, Andre Bernhard, Juerg Maibach, Rudolf Castiglione-Gertsch, Monica Coates, Alan S. Piccart, Martine J. Clemons, Mark J. Costantino, Joseph P. Wolmark, Norman TI A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37 SO CLINICAL BREAST CANCER LA English DT Article DE ipsilateral breast cancer; radiation therapy; recurrence ID LOCAL RECURRENCE; CONSERVATIVE SURGERY; RADIATION-THERAPY; TUMOR RECURRENCE; MULTIVARIATE-ANALYSIS; REGIONAL RECURRENCE; SALVAGE MASTECTOMY; SYSTEMIC THERAPY; RISK-FACTORS; PROGNOSIS AB In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2-positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator. C1 [Wapnir, Irene L.] Stanford Univ, Dept Surg, Sch Med, Stanford, CA 94305 USA. [Wapnir, Irene L.; Geyer, Charles E.; Anderson, Stewart J.; Robidoux, Andre; Clemons, Mark J.; Costantino, Joseph P.; Wolmark, Norman] Operat Off, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Wapnir, Irene L.; Geyer, Charles E.; Anderson, Stewart J.; Clemons, Mark J.; Costantino, Joseph P.; Wolmark, Norman] Ctr Biostat, Pittsburgh, PA USA. [Aebi, Stefan; Zahrieh, David; Gelber, Richard D.; Bernhard, Juerg; Maibach, Rudolf; Castiglione-Gertsch, Monica; Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Aebi, Stefan] Univ Hosp Bern, Dept Med Oncol, CH-3010 Bern, Switzerland. [Geyer, Charles E.; Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Zahrieh, David; Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Stewart J.; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. [Robidoux, Andre] CHU Montreal, Quebec City, PQ, Canada. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Piccart, Martine J.] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Piccart, Martine J.] Breast Int Grp, Brussels, Belgium. [Clemons, Mark J.] Princess Margaret Hosp Med Oncol, Toronto, ON, Canada. RP Wapnir, IL (reprint author), Stanford Univ, Dept Surg, Sch Med, 300 Pasteur Dr,H3625, Stanford, CA 94305 USA. EM wapnir@stanford.edu RI Aebi, Stefan/F-2004-2010; OI Aebi, Stefan/0000-0002-3383-9449; Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10CA-69651, CA-75362, U10CA-12027, U10CA-37377, U10CA-69974, UG1 CA189867] NR 40 TC 15 Z9 15 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2008 VL 8 IS 3 BP 287 EP 292 DI 10.3816/CBC.2008.n.035 PG 6 WC Oncology SC Oncology GA 315XZ UT WOS:000256914800013 PM 18650162 ER PT J AU Hamada, A Sissung, T Price, DK Danesi, R Chau, CH Sharifi, N Venzon, D Maeda, K Nagao, K Sparreboom, A Mitsuya, H Dahut, WL Figg, WD AF Hamada, Akinobu Sissung, Tristan Price, Douglas K. Danesi, Romano Chau, Cindy H. Sharifi, Nima Venzon, David Maeda, Kenji Nagao, Keisuke Sparreboom, Alex Mitsuya, Hiroaki Dahut, William L. Figg, William D. TI Effect of SLCO1B3 haplotype on testosterone transport and clinical outcome in Caucasian patients with androgen-independent prostatic cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID PHASE-II TRIAL; ORGANIC ANION TRANSPORTER; GENETIC POLYMORPHISMS; HORMONE LEVELS; RISK; SERUM; CYP17; EXPRESSION; SURAMIN; OATP8 AB Purpose: The organic anion transporter OATP1B3, encoded by SLCO1B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLCO1B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLCO1B3; (b) the expression of OATP1B3 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLCO1B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. Experimental Design: SLCO1B3 genotype was assessed in the NCl-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLCO1B3 variants. OATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLCO1B3 haplotypes and survival was examined in patients. Results: Cells transfected with wild-type (334T/699G) SLCO1B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses OATP1B3 compared with normal or benign hyperplastic tissue; patients with SLCO1B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42% versus 23%; P < 0.023) than patients carrying TT/AA and TG/GA haplotypes. Conclusions: The common SLCO1B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer. C1 [Mitsuya, Hiroaki] Kumamoto Univ, Dept Hematol & Infect Dsi, Kumamoto, Japan. [Hamada, Akinobu; Venzon, David] Kumamoto Univ, Dept Clin Pharmacol Sci, Kumamoto, Japan. [Danesi, Romano] Univ Pisa, Dept Internal Med, I-56100 Pisa, Italy. [Nagao, Keisuke] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Maeda, Kenji; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Dahut, William L.; Figg, William D.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Sissung, Tristan; Sparreboom, Alex; Figg, William D.] NCI, Clin Pharmacol Res Core, NIH, Bethesda, MD 20892 USA. [Hamada, Akinobu; Price, Douglas K.; Chau, Cindy H.; Sharifi, Nima; Figg, William D.] NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, NIH, Bldg 10 Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Nagao, Keisuke/J-5116-2013; Figg Sr, William/M-2411-2016 OI Nagao, Keisuke/0000-0002-7005-3138; FU Intramural NIH HHS [Z01 BC010453-06] NR 41 TC 91 Z9 94 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3312 EP 3318 DI 10.1158/1078-0432.CCR-07-4118 PG 7 WC Oncology SC Oncology GA 308RY UT WOS:000256408900012 PM 18519758 ER PT J AU Prasad, NB Somervell, H Tufano, RP Dackiw, APB Marohn, MR Califano, JA Wang, Y Westra, WH Clark, DP Umbricht, CB Libutti, SK Zeiger, MA AF Prasad, Nijaguna B. Somervell, Helina Tufano, Ralph P. Dackiw, Alan P. B. Marohn, Michael R. Califano, Joseph A. Wang, Yongchun Westra, William H. Clark, Douglas P. Umbricht, Christopher B. Libutti, Steven K. Zeiger, Martha A. TI Identification of genes differentially expressed in benign versus malignant thyroid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID DIPEPTIDYL-PEPTIDASE-IV; BREAST-CANCER; GENOMIC ORGANIZATION; COLORECTAL-CANCER; OVARIAN-CANCER; CELL-ADHESION; UP-REGULATION; CARCINOMA; SPARC; PROTEINS AB Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription - PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription - PCR data. Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions. C1 [Prasad, Nijaguna B.; Somervell, Helina; Dackiw, Alan P. B.; Marohn, Michael R.; Wang, Yongchun; Umbricht, Christopher B.; Zeiger, Martha A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. [Tufano, Ralph P.; Califano, Joseph A.] Johns Hopkins Univ, Sch Med, Dept Head & Neck Surg, Baltimore, MD 21287 USA. [Tufano, Ralph P.; Califano, Joseph A.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21287 USA. [Westra, William H.; Clark, Douglas P.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Libutti, Steven K.] NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Prasad, NB (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, 600 N Wolfe St,Carnegei 681, Baltimore, MD 21287 USA. EM nprasad1@jhmi.edu; mzeigerl@jhmi.edu FU NCI NIH HHS [R01 CA107247, R01 CA107247-01A1, R01 CA107247-05, R01-CA107247-01A1] NR 50 TC 49 Z9 52 U1 0 U2 6 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 JUN 1 PY 2008 VL 14 IS 11 BP 3327 EP 3337 DI 10.1158/1078-0432.CCR-07-4495 PG 11 WC Oncology SC Oncology GA 308RY UT WOS:000256408900014 PM 18519760 ER PT J AU Thorarinsdottir, HK Santi, M McCarter, R Rushing, EJ Cornelison, R Jales, A MacDonald, TJ AF Thorarinsdottir, Halldora K. Santi, Mariarita McCarter, Robert Rushing, Elisabeth J. Cornelison, Robert Jales, Alessandra MacDonald, Tobey J. TI Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-GRADE ASTROCYTOMA; CHILDRENS-CANCER-GROUP; GLIOBLASTOMA-MULTIFORME; BRAIN-STEM; PHASE-II; ANAPLASTIC ASTROCYTOMA; EGFR AMPLIFICATION; GENE AMPLIFICATION; IMATINIB MESYLATE; PATHWAY AB Purpose: We previously showed that overexpression of epidermal growth factor receptor (EGFR) is associated with malignant grade in childhood glioma. The objective of this study was to determine whether protein expression of EGFR or platelet-derived growth factor receptor (PDGFR) and their active signaling pathways are related to malignant histology, progression of disease, and worse survival. Experimental Design: Tissue microarrays were prepared from untreated tumors from 85 new glioma patients [22 high-grade gliomas (HGG) and 63 low-grade gliomas (LGG)] diagnosed at this institution from 1989 to 2004. Immunohistochemistry was used to assess total expression of EGFR, PDGFR, and PTEN and expression of phosphorylated EGFR, phosphorylated PDGFR alpha (p-PDGFR alpha), phosphorylated AKT, phosphorylated mitogen-activated protein kinase, and phosphorylated mammalian target of rapamycin. These results were correlated with clinicopathologic data, including extent of initial tumor resection, evidence of dissemination, tumor grade, proliferation index, and survival, as well as with Affymetrix gene expression profiles previously obtained from a subset of these tumors. Results: High expression of p-PDGFR alpha, EGFR, PDGFR beta, and phosphorylated EGFR was seen in 85.7%, 80.0%, 78.9%, and 47.4% of HGG and 40.0%, 87.1%, 41.7%, and 30.6% of LGG, respectively. However, high expression of p-PDGFR alpha and PDGFR beta was the only significant association with malignant histology (P = 0.031 and 0.005, respectively); only the loss of PTEN expression was associated with worse overall survival. None of these targets, either alone or in combination, was significantly associated with progression-free survival in either LGG or HGG. Conclusions: High PDGFR protein expression is significantly associated with malignant histology in pediatric gliomas, but it does not represent an independent prognostic factor. Deficient PTEN expression is associated with worse overall survival in HGG. C1 [Thorarinsdottir, Halldora K.; MacDonald, Tobey J.] Childrens Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. [Santi, Mariarita] Childrens Natl Med Ctr, Div Pathol, Washington, DC 20010 USA. [McCarter, Robert] Childrens Natl Med Ctr, Div Biostat, Washington, DC 20010 USA. [Cornelison, Robert] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [MacDonald, Tobey J.] Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC USA. [Cornelison, Robert; Jales, Alessandra; MacDonald, Tobey J.] George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA. [Rushing, Elisabeth J.] Armed Forces Inst Pathol, Dept Neuropathol, Washington, DC 20306 USA. RP MacDonald, TJ (reprint author), Childrens Natl Med Ctr, Div Hematol Oncol, 4th Floor W Wing,111 Michigan Ave NW, Washington, DC 20010 USA. EM tmacdona@cnmc.org RI MacDonald, Tobey/D-4554-2013 FU NCI NIH HHS [R01 CA111835, R01 CA111835-03] NR 40 TC 49 Z9 50 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 JUN 1 PY 2008 VL 14 IS 11 BP 3386 EP 3394 DI 10.1158/1078-0432.CCR-07-1616 PG 9 WC Oncology SC Oncology GA 308RY UT WOS:000256408900022 PM 18519768 ER PT J AU Bekaii-Saab, TS Liu, J Chan, KK Balcerzak, SP Ivy, PS Grever, MR Kraut, EH AF Bekaii-Saab, Tanios S. Liu, Jing Chan, Kenneth K. Balcerzak, Stanley P. Ivy, Percy S. Grever, Michael R. Kraut, Eric H. TI A phase I and pharmacokinetic study of weekly oxaliplatin followed by paclitaxel in patients with solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; GASTRIC-CANCER; SAFETY PROFILE; OVARIAN-CANCER; CISPLATIN; COMBINATION; TRIAL; FLUOROURACIL; LINES AB Purpose: Oxaliplatin and paclitaxel are widely used in treating solid tumors. We designed a phase I study with the purpose of determining the maximal tolerated dose and pharmacokinetic properties of weekly oxaliplatin followed by paclitaxel based on evidence suggesting that weekly administration of both drugs allows equivalent dose intensity with less neurotoxicity. Experimental Design: Twenty-three patients with advanced solid tumors were treated. Starting doses were 35 mg/m(2) oxaliplatin followed by 45 mg/m(2) paclitaxel weekly for 4 weeks every 6 weeks. Dose was escalated as follows: 45 mg/m(2) oxaliplatin and 45 mg/m(2) paclitaxel, 60 mg/m(2) oxaliplatin and 45 mg/m(2) paclitaxel, and 60 mg/m(2) oxaliplatin and 60 mg/m(2) paclitaxel. Pharmacokinetic studies were evaluated during the first course of therapy for oxaliplatin using population kinetics approach. Results: A total of 49 courses were administered. The dose-limiting toxicity was peripheral neuropathy with oxaliplatin and paclitaxel both at 60 mg/m2. There were three partial responses. There was evidence of pharmacokinetic interaction with a significant amount of total platinum (46.2-49.5%/24 h) eliminated in the urine in this group of patients, consistent with published data from others. The total body clearance values of plasma platinum and ultrafiltrable platinum were higher in this combination compared with corresponding values from our previous study with oxaliplatin only (P < 0.001). Conclusions: The recommended phase II dose of this combination is 60 mg/m(2) oxaliplatin followed by 45 mg/m(2) paclitaxel. Evidence of antitumor activity and acceptable toxicity with this combination and schedule warrants further investigation. We have obtained more definitive pharmacokinetic properties of oxaliplatin and confirmed its drug interaction with paclitaxel in the current sequence. C1 [Bekaii-Saab, Tanios S.; Chan, Kenneth K.; Balcerzak, Stanley P.; Grever, Michael R.; Kraut, Eric H.] Ohio State Univ, Dept Med, Div Hematol & Oncol, Coll Pharm, Columbus, OH 43210 USA. [Bekaii-Saab, Tanios S.] Ohio State Univ, Coll Pharm, Dept Pharmacol, Columbus, OH 43210 USA. [Liu, Jing; Chan, Kenneth K.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Ivy, Percy S.] NCI, Investigat Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kraut, EH (reprint author), Ohio State Univ, Dept Med, Div Hematol & Oncol, Coll Pharm, A434B Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM Eric.Kraut@osumc.edu RI Bekaii-Saab, Tanios/E-2733-2011 FU NCI NIH HHS [U01 CA076576, U01CA076576] NR 39 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3434 EP 3440 DI 10.1158/1078-0432.CCR-07-4903 PG 7 WC Oncology SC Oncology GA 308RY UT WOS:000256408900028 PM 18519774 ER PT J AU Ramalingam, SS Egorin, MJ Ramanathan, RK Remick, SC Sikorski, RP Lagattuta, TF Chatta, GS Friedland, DM Stoller, RG Potter, DM Ivy, SP Belani, CP AF Ramalingam, Suresh S. Egorin, Merrill J. Ramanathan, Ramesh K. Remick, Scot C. Sikorski, Rachel P. Lagattuta, Theodore F. Chatta, Gurkamal S. Friedland, David M. Stoller, Ronald G. Potter, Douglas M. Ivy, S. Percy Belani, Chandra P. TI A phase I study of 17-allylamino-17-demethoxygeldanamycin combined with paclitaxel in patients with advanced solid malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; REFRACTORY ADVANCED CANCERS; SHOCK-PROTEIN 90; BREAST-CANCER; 17-ALLYLAMINO GELDANAMYCIN; MEDIATED CYTOTOXICITY; HSP90; 17-DEMETHOXYGELDANAMYCIN; COMBINATION; INHIBITOR AB Background: 17-Allylamino-17-demethoxygeldanamycin (17-AAG) inhibits heat shock protein 90, promotes degradation of oncoproteins, and exhibits synergy with paclitaxel in vitro. We conducted a phase I study in patients with advanced malignancies to determine the recommended phase 11 dose of the combination of 17-AAG and paclitaxel. Methods: Patients with advanced solid malignancies that were refractory to proven therapy or without any standard treatment were included. 17-AAG (80-225 mg/m(2)) was given on days 1, 4, 8,11,15, and 18 of each 4-week cycle to sequential cohorts of patients. Paclitaxel (80-100 mg/m(2)) was administered on days 1, 8, and 15. Pharmacokinetic studies were conducted during cycle 1. Results: Twenty-five patients were accrued to five dose levels. The median number of cycles was 2. Chest pain (grade 3), myalgia (grade 3), and fatigue (grade 3) were dose-limiting toxicities at dose level 4 (225 mg/m(2) 17-AAG and 80 mg/m(2) paclitaxel). None of the six patients treated at dose level 3 with 17-AAG (175 mg/m2) and paclitaxel (80 mg/m(2)) experienced dose-limiting toxicity. Disease stabilization was noted in six patients, but there were no partial or complete responses. The ratio of paclitaxel area under the concentration to time curve when given alone versus in combination with 17-AAG was 0.97 +/- 0.20. The ratio of end-of-infusion concentration of 17-AAG (alone versus in combination with paclitaxel) was 1.14 +/- 0.51. Conclusions: The recommended phase 11 dose of twice-weekly 17-AAG (175 mg/m(2)) and weekly paclitaxel (80 mg/m(2)/wk) was tolerated well. There was no evidence of drug-drug pharmacokinetic interactions. C1 [Ramalingam, Suresh S.; Egorin, Merrill J.; Ramanathan, Ramesh K.; Chatta, Gurkamal S.; Belani, Chandra P.] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15260 USA. [Ramalingam, Suresh S.; Egorin, Merrill J.; Ramanathan, Ramesh K.; Sikorski, Rachel P.; Lagattuta, Theodore F.; Chatta, Gurkamal S.; Friedland, David M.; Stoller, Ronald G.; Potter, Douglas M.; Belani, Chandra P.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15260 USA. [Potter, Douglas M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. [Remick, Scot C.] Univ Hosp Case Med Ctr, Case Comprehens Canc Ctr, Dev Therapeut Program, Cleveland, OH USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Ramalingam, SS (reprint author), Emory Univ, Winship Canc Inst, 1365 Clifton Rd,Suite C-5090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu OI Belani, Chandra/0000-0001-5049-5329 FU NCI NIH HHS [P30 CA47904, U01 CA 62502, U01 CA099168]; NCRR NIH HHS [5M01-RR 00056, M01 RR000080, M01-RR00080] NR 35 TC 49 Z9 49 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 JUN 1 PY 2008 VL 14 IS 11 BP 3456 EP 3461 DI 10.1158/1078-0432.CCR-07-5088 PG 6 WC Oncology SC Oncology GA 308RY UT WOS:000256408900031 PM 18519777 ER PT J AU Beumer, JH Eiseman, JL Parise, RA Joseph, E Covey, JM Egorin, MJ AF Beumer, Jan H. Eiseman, Julie L. Parise, Robert A. Joseph, Erin Covey, Joseph M. Egorin, Merrill J. TI Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and Bioavailability in mice by 3,4,5,6-tetrahydrouridine SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTIDINE DEAMINASE; DOSE-RATE; 2',2'-DIFLUORODEOXYCYTIDINE GEMCITABINE; DEOXYCYTIDYLATE DEAMINASE; CYTOSINE-ARABINOSIDE; L1210-LEUKEMIC MICE; ORAL ACTIVITY; TETRAHYDROURIDINE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; TUMORS AB Purpose: In vivo, 2',2'-difluoro-2'-deoxycytidine (dFdC) is rapidly inactivated by gut and liver cytidine deaminase (CD) to 2',2'-difluoro-2'-deoxyuridine (dFdU). Consequently, dFdC has poor oral bioavailability and is administered i.v., with associated costs and limitations in administration schedules. 3,4,5,6 -Tetrahydrouridine (THU) is a potent CD inhibitor with a 20% oral bioavailability. We investigated the ability of THU to decrease elimination and first-pass effect by CD, thereby enabling oral dosing of dFdC. Experimental Design: A liquid chromatography-tandem mass spectrometry assay was developed for plasma dFdC and dFdU. Mice were\ dosed with 100 mg/kg dFdC i. v. or orally with or without 100 mg/kg THU i.v. or orally. At specified times between 5 and 1,440 min, mice (n = 3) were euthanized. dFdC, dFdU, and THU concentrations were quantitated in plasma and urine. Results: THU i.v. and orally produced concentrations > 4 mu g/mL for 3 and 2 h, respectively, whereas concentrations of > 1 mu g/mL have been associated with near-complete inhibition of CD in vitro. THU i.v. decreased plasma dFdU concentrations but had no effect on dFdC plasma area under the plasma concentration versus time curve after i.v. dFdC dosing. Both THU i.v. and orally substantially increased oral bioavailability of dFdC. Absorption of dFdC orally was 59%, but only 10% passed liver and gut CD and eventually reached the systemic circulation. Coadministration of THU orally increased dFdC oral bioavailability from 10% to 40%. Conclusions: Coadministration of THU enables oral dosing of dFdC and warrants clinical testing. Oral dFdC treatment would be easier and cheaper, potentially prolong d FdC exposure, and enable exploration of administration schedules considered impractical by the i.v. route. C1 [Beumer, Jan H.; Eiseman, Julie L.; Parise, Robert A.; Joseph, Erin; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. [Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [Eiseman, Julie L.; Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. [Covey, Joseph M.] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Rockville, MD USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G27D,Hillman Res Pavill,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerjh@upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU NCI NIH HHS [P30-CA47904, N01-CM-52202] NR 41 TC 24 Z9 24 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3529 EP 3535 DI 10.1158/1078-0432.CCR-07-4885 PG 7 WC Oncology SC Oncology GA 308RY UT WOS:000256408900040 PM 18519786 ER PT J AU Garnett, CT Schlom, J Hodge, JW AF Garnett, Charlie T. Schlom, Jeffrey Hodge, James W. TI Combination of docetaxel and recombinant vaccine enhances T-Cell responses and antitumor activity: Effects of docetaxel on immune enhancement SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN GENE; NECROSIS-FACTOR-ALPHA; RANDOMIZED PHASE-II; CEA TRANSGENIC MICE; CANCER VACCINES; PACLITAXEL ENHANCE; PROSTATE-CANCER; BREAST-CANCER; SELF-ANTIGEN AB Purpose: Taxanes comprise some of the most widely used cancer chemotherapeutic agents. Members of this drug family, including docetaxel, are commonly used to treat breast, prostate, and lung cancers, among others. This study was designed to determine if this taxane has the ability to modulate components of the immune system independent of antitumor activity and to investigate the potential synergistic activities of the combination of docetaxel and vaccine therapy. Experimental Design: We examined the in vivo effects of docetaxel on immune-cell subsets and on the function of CD4(+), CD8(+), and regulatory T-cell (Treg) populations in response to antigen-specific vaccination. We also examined the antitumor effects of the combination of docetaxel and vaccine in a preclinical model in which docetaxel has no observable effect on tumor growth. Results:These studies show for the first time that (a) docetaxel modulates CD4(+), CD8(+), CD19(+), natural killer cell, and Treg populations in non - tumor-bearing mice; (b) unlike cyclophosphamide, docetaxel does not inhibit the function of Tregs; (c) docetaxel enhances CD8(+) but not CD4(+) response to CD3 cross-linking; (d) docetaxel given after vaccination provides optimal enhancement of immune response to recombinant viral vaccines; (e) docetaxel combined with recombinant viral vaccine is superior to either agent alone at reducing tumor burden; and (f) docetaxel plus vaccine increases antigen-specific T-cell responses to antigen in the vaccine, as well as to cascade antigens derived from the tumor. Conclusions: These findings suggest potential clinical benefit for the combined use of docetaxel and recombinant cancer vaccines. C1 [Garnett, Charlie T.; Schlom, Jeffrey; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural NIH HHS [Z01 BC010661-03] NR 40 TC 109 Z9 113 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3536 EP 3544 DI 10.1158/1078-0432.CCR-07-4025 PG 9 WC Oncology SC Oncology GA 308RY UT WOS:000256408900041 PM 18519787 ER PT J AU Seegmiller, JC Sviridov, D Hortin, GL Shaikh, A Larson, TS Lieske, JC AF Seegmiller, J. C. Sviridov, D. Hortin, G. L. Shaikh, A. Larson, T. S. Lieske, J. C. TI Comparison of urinary albumin measurements by immunoassays versus liquid chromatography-tandem mass spectrometry SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Seegmiller, J. C.; Shaikh, A.; Larson, T. S.; Lieske, J. C.] Mayo Clin, Rochester, MN USA. [Sviridov, D.; Hortin, G. L.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2008 VL 54 IS 6 SU S MA D119 BP A182 EP A182 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700564 ER PT J AU Sethi, AA Sampson, M Warnick, R Nakajima, K Nordestgaard, B Tybjaerg-Hansen, A Remaley, A AF Sethi, A. A. Sampson, M. Warnick, R. Nakajima, K. Nordestgaard, B. Tybjaerg-Hansen, A. Remaley, A. TI Pre-beta HDL is a strong positive diagnostic risk marker for Ischemic Heart Disease in subjects with both high and low HDL-C levels. The Copenhagen City Heart Study SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Sethi, A. A.; Sampson, M.; Remaley, A.] NIH, Bethesda, MD 20892 USA. [Warnick, R.] Berkeley HeartLab, Burlingame, CA USA. [Nakajima, K.] Tokai Univ, Sch Med, Dept Forens Med, Hiratsuka, Kanagawa 25912, Japan. [Nordestgaard, B.] Herlev Univ Hosp, DK-2730 Herlev, Denmark. [Tybjaerg-Hansen, A.] Univ Copenhagen Hosp, DK-2100 Copenhagen, Denmark. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2008 VL 54 IS 6 SU S MA D32 BP A154 EP A154 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700478 ER PT J AU Sviridov, D Hortin, GL Drake, SK Aponte, A Edelman, LS Roberts, WL AF Sviridov, D. Hortin, G. L. Drake, S. K. Aponte, A. Edelman, L. S. Roberts, W. L. TI Urinary protein excretion by patients with burn injury: Proteinuria without albuminuria SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Sviridov, D.; Hortin, G. L.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Drake, S. K.] NIH, Crit Care Med Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Aponte, A.] NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. [Edelman, L. S.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Roberts, W. L.] ARUP Labs, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2008 VL 54 IS 6 SU S MA D120 BP A182 EP A182 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700565 ER PT J AU Crawford, NPS Walker, RC Lukes, L Officewala, JS Williams, RW Hunter, KW AF Crawford, Nigel P. S. Walker, Renard C. Lukes, Luanne Officewala, Jennifer S. Williams, Robert W. Hunter, Kent W. TI The Diasporin Pathway: a tumor progression-related transcriptional network that predicts breast cancer survival SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE metastasis; mouse models; expression quantitative trait loci; gene expression; breast cancer; progression; survival ID BROMODOMAIN PROTEIN BRD4; TRANSGENIC MOUSE MODEL; COMPLEX TRAIT ANALYSIS; GENE-EXPRESSION; METASTASIS SUPPRESSOR; MAMMARY-TUMORS; SIGNATURE; DISEASE; NECDIN; CELLS AB Microarray expression signature analyses have suggested that extracellular matrix (ECM) gene dysregulation is predictive of metastasis in both mouse mammary tumorigenesis and human breast cancer. We have previously demonstrated that such ECM dysregulation is influenced by hereditary germline-encoded variation. To identify novel metastasis efficiency modifiers, we performed expression QTL (eQTL) mapping in recombinant inbred mice by characterizing genetic loci modulating metastasis-predictive ECM gene expression. Three reproducible eQTLs were observed on chromosomes 7, 17 and 18. Candidate genes were identified by correlation analyses and known associations with metastasis. Seven candidates were identified (Ndn, Pi16, Luc7l, Rrp1b, Brd4, Centd3 and Csf1r). Stable transfection of the highly metastatic Mvt-1 mouse mammary tumor cell line with expression vectors encoding each candidate modulated metastasis-predictive ECM gene expression. Implantation of these cells into mice demonstrated that candidate gene ectopic expression impacts tumor progression. Gene expression analyses facilitated the construction of a transcriptional network that we have termed the 'Diasporin Pathway'. This pathway contains the seven candidates, as well as metastasis-predictive ECM genes and metastasis suppressors. Brd4 and Rrp1b appear to form a central node within this network, which likely is a consequence of their physical interaction with the metastasis efficiency modifier Sipa1. Furthermore, we demonstrate that the microarray gene expression signatures induced by activation of ECM eQTL genes in the Mvt-1 cell line can be used to accurately predict survival in a human breast cancer cohort. These data imply that the Diasporin Pathway may be an important nexus in tumor progression in both mice and humans. C1 [Crawford, Nigel P. S.; Walker, Renard C.; Lukes, Luanne; Officewala, Jennifer S.; Williams, Robert W.; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN USA. RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov OI Williams, Robert/0000-0001-8924-4447 FU Intramural NIH HHS [Z01 CP010146-07, Z99 CA999999] NR 43 TC 41 Z9 42 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JUN PY 2008 VL 25 IS 4 BP 357 EP 369 DI 10.1007/s10585-008-9146-6 PG 13 WC Oncology SC Oncology GA 306MT UT WOS:000256253200008 PM 18301994 ER PT J AU Loomba, R Rowley, AK Wesley, R Smith, KG Liang, TJ Pucino, F Csako, G AF Loomba, Rohit Rowley, Ayana K. Wesley, Robert Smith, Karen G. Liang, T. Jake Pucino, Frank Csako, Gyorgy TI Hepatitis B immunoglobulin and lamivudine improve hepatitis B-related outcomes after liver transplantation: Meta-analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID IMMUNE GLOBULIN; VIRUS RECURRENCE; ANTI-HBS; PREVENTION; PROPHYLAXIS; COMBINATION; THERAPY; HBIG; REPLICATION; MONOTHERAPY AB Background & Aims: HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting. Methods: We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model. Results: Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03-0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02-0.33) and 0.02 (95% CI, 0.06-0.82), respectively. Conclusions: Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants. C1 [Loomba, Rohit; Liang, T. Jake] NIDDK, Liver Dis Branch, DHHS, NIH, Bethesda, MD 20892 USA. [Rowley, Ayana K.; Pucino, Frank] Dept Pharm, Bethesda, MD USA. [Smith, Karen G.] Natl Inst Hlth Lib, Bethesda, MD USA. [Wesley, Robert] Biostat & Clin Epidemiol Serv, Bethesda, MD USA. [Csako, Gyorgy] Natl Inst Hlth, Ctr Clin, Dept Lab Med, DHHS, Bethesda, MD USA. [Loomba, Rohit] Univ Calif San Diego, Dept Med, Div Gastroenterol, San Diego, CA 92103 USA. RP Loomba, R (reprint author), NIDDK, Liver Dis Branch, DHHS, NIH, CIRC-4-5722,MSC-1614,10 Ctr Dr, Bethesda, MD 20892 USA. EM roloomba@ucsd.edu FU Intramural NIH HHS [Z01 DK054501-11] NR 28 TC 51 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2008 VL 6 IS 6 BP 696 EP 700 DI 10.1016/j.cgh.2008.02.055 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 314AA UT WOS:000256779900018 PM 18456569 ER PT J AU Hirai, H Miura, J Hu, YF Larsson, H Larsson, K Lernmark, A Ivarsson, SA Wu, TX Kingman, A Tzioufas, AG Notkins, AL AF Hirai, Hiroki Miura, Junnosuke Hu, Yafang Larsson, Helena Larsson, Karin Lernmark, Ake Ivarsson, Sten-A. Wu, Tianxia Kingman, Albert Tzioufas, Athanasios G. Notkins, Abner L. TI Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens SO CLINICAL IMMUNOLOGY LA English DT Article DE autoantibodies; autoantigens; GAD65; IA-2; protein tyrosine; phosphatase; proteome; secretory vesicles; type 1 diabetes ID GLUTAMIC-ACID DECARBOXYLASE; T-CELLS; TYROSINE-PHOSPHATASE; TRANSMEMBRANE PROTEIN; MAJOR AUTOANTIGEN; IA-2 BETA; AUTOANTIBODIES; INSULIN; MELLITUS; CHILDREN AB The four major autoantigens (IA-2, IA-2 beta, GAD65 and insulin) of type 1 diabetes are all associated with dense core or synaptic vesicles. This raised the possibility that other secretory vesicle-associated proteins might be targets of the autoimmune response in type 1 diabetes. To test this hypothesis 56 proteins, two-thirds of which are associated with secretory vesicles, were prepared by in vitro transcription/translation and screened for autoantibodies by liquid phase radioimmunoprecipitation. Two secretory vesicle-associated proteins, VAMP2 and NPY, were identified as new minor autoantigens with 21% and 9%, respectively, of 200 type 1 diabetes sera reacting positively. These findings add support to the hypothesis that secretory vesicle-associated proteins are particularly important, but not the exclusive, targets of the autoimmune response in type 1 diabetes. Selective screening of the human proteome offers a useful approach for identifying new autoantigens in autoimmune diseases. (c) 2008 Elsevier Inc. All rights reserved. C1 [Hirai, Hiroki; Miura, Junnosuke; Hu, Yafang; Tzioufas, Athanasios G.; Notkins, Abner L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Larsson, Helena; Larsson, Karin; Ivarsson, Sten-A.] Lund Univ, Dept Paediat, Malmo Univ Hosp, Malmo, Sweden. [Lernmark, Ake] Univ Washington, Dept Med, RH Williams Lab, Seattle, WA USA. [Wu, Tianxia; Kingman, Albert] Natl Inst Dent & Craniofacial Res, Div Clin Res & Hlth Promot, NIH, Bethesda, MD 20892 USA. RP Hirai, H (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM hhirai@mail.nih.gov FU Intramural NIH HHS [Z01 DE000423-22] NR 42 TC 18 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2008 VL 127 IS 3 BP 366 EP 374 DI 10.1016/j.clim.2008.01.018 PG 9 WC Immunology SC Immunology GA 308FL UT WOS:000256373600014 PM 18359275 ER PT J AU Najvar, LK Bocanegra, R Wiederhold, NP Lambros, C Najarian, N Patterson, TF Graybill, JR AF Najvar, L. K. Bocanegra, R. Wiederhold, N. P. Lambros, C. Najarian, N. Patterson, T. F. Graybill, J. R. TI Therapeutic and prophylactic efficacy of aminocandin (IP960) against disseminated candidiasis in mice SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article; Proceedings Paper CT 45th Interscience Conference on Antimicrobial Agents and Chemotherapy CY DEC 16-19, 2005 CL Washington, DC DE aminocandin; antifungal prophylaxis; Candida albicans; extended interval dosing; invasive candidiasis; mouse model ID STEM-CELL TRANSPLANTATION; AMPHOTERICIN-B; MURINE MODEL; SYSTEMIC CANDIDIASIS; INVASIVE CANDIDIASIS; FUNGAL-INFECTIONS; FLUCONAZOLE; MICAFUNGIN; PHARMACODYNAMICS; CASPOFUNGIN AB Extended interval dosing of the echinocandins has been suggested as a potential strategy to overcome the need for daily intravenous administration. This study evaluated the therapeutic and prophylactic efficacy of single doses of aminocandin, a new echinocandin in preclinical development, in a murine model of invasive candidiasis. For therapy, groups of mice were infected with Candida albicans, followed by a single dose of aminocandin (1-15 mg/kg) or placebo (mannitol 5% w/v) administered 1 day after inoculation. As prophylaxis, mice were given a single dose (5 or 30 mg/kg) of aminocandin, caspofungin, or placebo at increasing intervals between dose and inoculation. In both treatment and prophylaxis studies, survival was assessed at 21 days post-inoculation. The reduction in fungal burden was assessed in kidney tissue on day 8 post-inoculation. For treatment, single doses of aminocandin of >= 2.5 mg/kg prolonged survival significantly. In addition, the two doses evaluated for reductions in fungal burden (5 and 15 mg/kg) revealed fungicidal activity. As prophylaxis, both aminocandin and caspofungin 5 and 30 mg/kg prolonged survival when given 7 days before inoculation. Aminocandin and caspofungin 30 mg/kg were both able to prolong survival when the interval between dose and inoculation was increased to 10 days. When this interval was extended to 14 days, only aminocandin 30 mg/kg prolonged survival and reduced fungal burden. These results demonstrate that single doses of aminocandin are effective as treatment and prophylaxis, and suggest that extended interval dosing may be a useful strategy for treating invasive candidiasis. C1 [Najvar, L. K.; Bocanegra, R.; Wiederhold, N. P.; Patterson, T. F.; Graybill, J. R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, MC 7881, San Antonio, TX 78229 USA. [Wiederhold, N. P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Lambros, C.] NIAID, NIH, Bethesda, MD 20892 USA. [Najarian, N.] Indevus, Lexington, MA USA. RP Najvar, LK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, MC 7881, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM najvar@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU NIAID NIH HHS [N01-AI-25475] NR 18 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD JUN PY 2008 VL 14 IS 6 BP 595 EP 600 DI 10.1111/j.1469-0691.2008.01994.x PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 297FI UT WOS:000255602100011 PM 18397335 ER PT J AU Carvalho, R Johnson, E Kozlosky, M Scheimann, AO AF Carvalho, Ryan Johnson, Elizabeth Kozlosky, Merel Scheimann, Ann O. TI Clinical profile of the overweight child in the new millennium SO CLINICAL PEDIATRICS LA English DT Article DE overweight; morbidity; child; nibbling; fast-food consumption; television eating ID BLOOD-PRESSURE; BODY-MASS; OBESITY; RISK; ADOLESCENTS; DIETARY AB Background In conjunction with the rising prevalence of obesity during the past several decades, the clinical profile of the obese child has changed. Hypothesis. Environmental influences and eating practices have had an impact on the presence of medical morbidities among obese children. Design Retrospective chart review of data collected from 90 children entering into a pediatric weight management program was performed. Fisher's exact tests and Wilcoxon rank sum tests were used to compare outcomes between subpopulations. Results There was greater elevation in systolic blood pressure among children who ate in front of the television (P =.03) and a greater degree of fast-food consumption among children with more than 3 medical morbidities (P =.02). Breast-feeding did not have a protective effect on the degree of obesity (P =.02). Conclusion Aggressive assessment for symptoms should be an important part of evaluating the overweight child. Environmental influences and social feeding practices can counteract the protective effects of breast-feeding in infancy. C1 [Scheimann, Ann O.] Johns Hopkins Univ, Sch Med, Div Pediat Gastroenterol & Nutr, Baltimore, MD 21287 USA. [Carvalho, Ryan] Wright State Univ, Sch Med, Dept Pediat, Dayton, OH 45435 USA. [Johnson, Elizabeth] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Kozlosky, Merel] NIH, Ctr Clin, Dept Nutr, Bethesda, MD 20892 USA. [Kozlosky, Merel] Johns Hopkins Childrens Ctr, Div Pediat Gastroenterol & Nutr, Baltimore, MD USA. RP Scheimann, AO (reprint author), Johns Hopkins Univ, Sch Med, Div Pediat Gastroenterol & Nutr, 600 N Wolfe St Brady 320, Baltimore, MD 21287 USA. EM ascheim1@jhmi.edu NR 25 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JUN PY 2008 VL 47 IS 5 BP 476 EP 482 DI 10.1177/0009922807311733 PG 7 WC Pediatrics SC Pediatrics GA 298DW UT WOS:000255667600008 PM 18413697 ER PT J AU Signore, C Klebanoff, M AF Signore, Caroline Klebanoff, Mark TI Neonatal morbidity and mortality after elective cesarean delivery SO CLINICS IN PERINATOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; TERM BREECH TRIAL; CEREBRAL-PALSY; DECISION-ANALYSIS; RISK-FACTORS; SHOULDER DYSTOCIA; PERINATAL DEATH; SECTION; MODE; LABOR AB This article explores the effects of elective cesarean delivery (ECD) at term on neonatal morbidity and mortality Available data have limitations, and do not provide conclusive evidence regarding the safety of planned ECD versus planned vaginal delivery. Some data suggest an association between ECD and increased neonatal respiratory morbidity and lacerations, and possibly decreased central and peripheral nervous system injury. Potentially increased risks of neonatal mortality with ECD at term may be counterbalanced by risks for fetal demise in ongoing pregnancies. Patients and physicians considering ECD should review competing risks and benefits; further research is needed to inform these discussions. C1 [Signore, Caroline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Klebanoff, Mark] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Signore, C (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA. EM signorec@mail.NIH.gov FU Intramural NIH HHS [Z99 HD999999] NR 62 TC 24 Z9 28 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 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD JUN PY 2008 VL 35 IS 2 BP 361 EP + DI 10.1016/j.clp.2008.03.009 PG 12 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 308SK UT WOS:000256410100006 PM 18456074 ER PT J AU Geisler, S Trimble, M AF Geisler, Stefanie Trimble, Michael TI The lateral habenula: No longer neglected SO CNS SPECTRUMS LA English DT Article ID VENTRAL TEGMENTAL AREA; DORSAL RAPHE NUCLEUS; BASAL FOREBRAIN ORGANIZATION; FOS-LIKE IMMUNOREACTIVITY; MEDIAL PREFRONTAL CORTEX; EFFERENT CONNECTIONS; MATERNAL-BEHAVIOR; DOPAMINE NEURONS; SELF-STIMULATION; HORSERADISH-PEROXIDASE C1 [Trimble, Michael] Queen Sq, Inst Neurol, London, England. RP Geisler, S (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 08A729, Baltimore, MD 21224 USA. EM geislers@intra.nida.nih.gov NR 92 TC 71 Z9 72 U1 0 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2008 VL 13 IS 6 BP 484 EP 489 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 315XW UT WOS:000256914500009 PM 18567972 ER PT J AU Horkay, F Hammouda, B AF Horkay, Ferenc Hammouda, Boualem TI Small-angle neutron scattering from typical synthetic and biopolymer solutions SO COLLOID AND POLYMER SCIENCE LA English DT Review DE small-angle neutron scattering; polymer solution; solvation; clustering; hydrophilic; hydrophobic interaction ID MIXTURES; GELS AB Small-angle neutron scattering (SANS) has been used to investigate the solution properties of four model polymers, two poly-amino acids [poly(lysine) and poly(proline)], and two water-soluble synthetic polymers [poly(acrylic acid) and poly(ethylene oxide)]. In each case, one of the two polymers is charged, while the other is neutral. SANS measurements were made in the semi-dilute concentration regime in two different solvents [d-water and d-ethylene glycol]. The scattering signals were decomposed into low-Q clustering and high-Q solvation contributions. The temperature dependence of the scattering parameters was determined for poly(lysine) and poly(ethylene oxide) solutions over the temperature range of 13 to 82 degrees C. Analysis of the SANS spectra revealed that with increasing temperature, the solvation intensity increased in both solvents, while the clustering intensity increased in d-water and decreased in d-ethylene glycol. Significant differences were observed between the SANS spectra of charged and neutral polymer solutions. However, biopolymers and synthetic polymers exhibited qualitatively similar behavior. C1 [Horkay, Ferenc] NICHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. [Hammouda, Boualem] Natl Inst Stand & Technol, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Horkay, F (reprint author), NICHD, NIH, Lab Integrat & Med Biophys, 13 S Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov NR 27 TC 22 Z9 22 U1 3 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0303-402X J9 COLLOID POLYM SCI JI Colloid Polym. Sci. PD JUN PY 2008 VL 286 IS 6-7 BP 611 EP 620 DI 10.1007/s00396-008-1849-3 PG 10 WC Chemistry, Physical; Polymer Science SC Chemistry; Polymer Science GA 304DD UT WOS:000256089300001 ER PT J AU Kimple, AJ Yasgar, A Hughes, M Jadhav, A Willard, FS Muller, RE Austin, CP Inglese, J Ibeanu, GC Siderovski, DP Simeonov, A AF Kimple, Adam J. Yasgar, Adam Hughes, Mark Jadhav, Ajit Willard, Francis S. Muller, Robin E. Austin, Christopher P. Inglese, James Ibeanu, Gordon C. Siderovski, David P. Simeonov, Anton TI A high throughput fluorescence polarization assay for inhibitors of the GoLoco motif/G-alpha interaction SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE fluorescence anisotropy; fluorescence polarization; GoLoco motif; heterotrimeric G-proteins; high throughput screening ID DISSOCIATION INHIBITOR; PROTEIN HYDRODYNAMICS; SCREENING ASSAYS; ELEGANS EMBRYOS; CELL-DIVISION; BINDING; LIGAND; ACTIVATION; DROSOPHILA; POLARITY AB The GoLoco motif is a short G alpha binding polypeptide sequence. It is often found in proteins that regulate cell-surface receptor signaling, such as RGS12, as well as in proteins that regulate mitotic spindle orientation and force generation during cell division, such as GPSM2/LGN. Here, we describe a high throughput fluorescence polarization (FP) assay using fluorophore-labeled GoLoco motif peptides for identifying inhibitors of the GoLoco motif interaction with the G-protein alpha subunit G(i1). The assay exhibits considerable stability over time and is tolerant to DMSO up to 5%. The Z'-factors for robustness of the GPSM2 and RGS12 GoLoco motif assays in a 96-well plate format were determined to be 0.81 and 0.84, respectively; the latter assay was run in a 384-well plate format and produced a Z'-factor of 0.80. To determine the screening factor window (Z-factor) of the RGS12 GoLoco motif screen using a small molecule library, the NCI Diversity Set was screened. The Z-factor was determined to be 0.66, suggesting that this FP assay would perform well when developed for 1,536-well format and scaled up to larger libraries. We then miniaturized to a 4 mu L final volume a pair of FP assays utilizing fluorescein- (green) and rhodamine- (red) labeled RGS12 GoLoco motif peptides. In a fully-automated run, the Sigma-Aldrich LOPAC(1280) collection was screened three times with every library compound being tested over a range of concentrations following the quantitative high throughput screening (qHTS) paradigm; excellent assay performance was noted with average Z-factors of 0.84 and 0.66 for the green- and red-label assays, respectively. C1 [Yasgar, Adam; Jadhav, Ajit; Austin, Christopher P.; Inglese, James; Simeonov, Anton] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Kimple, Adam J.; Willard, Francis S.; Muller, Robin E.; Siderovski, David P.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. [Kimple, Adam J.; Willard, Francis S.; Muller, Robin E.; Siderovski, David P.] Univ N Carolina, Dept Pharmacol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Hughes, Mark; Ibeanu, Gordon C.] N Carolina Cent Univ, BRITE Inst, Durham, NC 27707 USA. RP Simeonov, A (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM asimeono@mail.nih.gov OI Siderovski, David/0000-0002-0688-8210 FU NIMH NIH HHS [F30 MH074266-02, F30 MH074266, F30 MH074266-01A1, F30MH074266]; NINDS NIH HHS [R03 NS053754, R03 NS053754-01, R03 NS053754-01S1] NR 57 TC 18 Z9 18 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD JUN PY 2008 VL 11 IS 5 BP 396 EP 409 DI 10.2174/138620708784534770 PG 14 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 310ZD UT WOS:000256568700007 PM 18537560 ER PT J AU Baxa, U AF Baxa, Ulrich TI Structural basis of infectious and non-infectious amyloids SO CURRENT ALZHEIMER RESEARCH LA English DT Review ID HET-S PRION; SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; SUPERPLEATED BETA-STRUCTURE; PROTEIN-A AMYLOIDOSIS; IN-VITRO; FIBRIL FORMATION; PODOSPORA-ANSERINA; FORMING DOMAIN; CORE STRUCTURE AB Amyloid fibrils are elongated protein aggregates well known for their association with many human diseases. However, similar structures have also been found in other organisms and amyloid fibrils can also be formed in vitro by other proteins usually under non-physiological conditions. In all cases, these fibrils assemble in a nucleated polymerization reaction with a pronounced lag phase that can be eliminated by supplying pre-formed fibrils as seeds. Once formed, the fibrils are usually very stable, except for their tendency to break into smaller pieces forming more growing ends in the process. These properties give amyloid fibers a self-replicating character dependent only on a source of soluble protein. For some systems and under certain circumstances this can lead to infectious protein structures, so-called prions, that can be passed from one organism to another as in the transmissible spongiform encephalopathies and in fungal prion systems. Structural details about these processes have emerged only recently, mostly on account of the inability of traditional high-resolution methods to deal with insoluble, filamentous specimens. In consequence, current models for amyloid fibrils are based on fewer constraints than common atomic-resolution structures. This review gives an overview of the constraints used for the development of amyloid models and the methods used to derive them. The principally possible structures will be introduced by discussing current models of amyloid fibrils from Alzheimer's peptide, amylin and several fungal systems. The infectivity of some amyloids under specific conditions might not be due to a principal structural difference between infectious and non-infectious amyloids, but could result from an interplay of the rates for filament nucleation, growth, fragmentation, and clearance. C1 [Baxa, Ulrich] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Baxa, U (reprint author), Bldg 50,Room 1509,50 S Drive MSC 8025, Bethesda, MD 20892 USA. EM baxau@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 121 TC 16 Z9 16 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JUN PY 2008 VL 5 IS 3 BP 308 EP 318 DI 10.2174/156720508784533367 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 310ZN UT WOS:000256569700007 PM 18537545 ER PT J AU Horvath, A Stratakis, CA AF Horvath, Anelia Stratakis, Constantine A. TI Unraveling the molecular basis of micronodular adrenal hyperplasia SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE adrenocortical tumors; cyclic-AMP signaling; phosphodiesterases; protein kinase A ID PROTEIN-KINASE-A; NODULAR ADRENOCORTICAL DISEASE; FAMILIAL CARDIAC MYXOMAS; SUBUNIT TYPE 1A; CARNEY-COMPLEX; REGULATORY SUBUNIT; ENDOCRINE OVERACTIVITY; CUSHING-SYNDROME; SPOTTY PIGMENTATION; PRKAR1A MUTATION AB Purpose of review The present review discusses the molecular basis of micronodular adrenal hyperplasia. It focuses on the role of genetic defects in cyclic-AMP (cAMP) signaling-related molecules, namely PRKAR1A, GNAS, PDE11A, and PDE8B in the predisposition to tumor formation. This review also discusses the involvement of cAMP signaling and related pathways and their impact on the adrenocortical tumor formation. Recent findings Molecular abnormalities in the phosphodiesterases family are the most recently discovered genetic abnormalities that predispose individuals to various adrenocortical tumors. In contrast to GNAS and PRKAR1A, defects in phosphodiesterases are associated more frequently with incomplete penetrance. Summary Recent findings indicate the importance of cAMP signaling for normal adrenocortical functioning and the sensitivity of the adrenal gland to subtle alterations in cAMP levels. The identification of low-penetrance mutations in more than one phosphodiesterase in patients with adrenocortical hyperplasia is suggestive for a complementary role of the different phosphodiesterases in adrenal gland abnormalities and possible involvement of other members of this pathway in adrenocortical tumor defects. C1 [Horvath, Anelia; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, PDEGEN, NICHD,NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, PDEGEN, NICHD,NIH, 10 Ctr Dr,CRC,Room 1E-3330, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU National Institutes of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland; NICHD, NIH [Z01-HD-000642-04] FX Dr Horvath's fellowship is supported by the Intramural Program of the National Institutes of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland; funds for this project are provided by the NICHD, NIH intramural project Z01-HD-000642-04 to Dr Constantine A. Stratakis. NR 53 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2008 VL 15 IS 3 BP 227 EP 233 DI 10.1097/MED.0b013e3282fe7416 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V14ST UT WOS:000207754800002 PM 18438169 ER PT J AU Chu, LW Reichardt, JKV Hsing, AW AF Chu, Lisa W. Reichardt, Juergen K. V. Hsing, Ann W. TI Androgens and the molecular epidemiology of prostate cancer SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE androgen metabolism; androgen signaling; prostate cancer epidemiology AB Purpose of review Despite clinical and experimental evidence that show androgens are important in prostate carcinogenesis, epidemiologic studies of serum androgens have been inconclusive. In this review, we summarize the current state of the literature and provide insights and direction for epidemiologic research on androgens and prostate cancer. Recent findings To date, data on serum androgens in prostate cancer remain inconclusive. Large studies on variants in some androgen-metabolizing genes [SRD5A2, CYP17A1, and hydroxysteroid dehydrogenase (HSD) 17B1] do not show a convincing links to prostate cancer, though there are insufficient data to draw conclusions on other genes related to androgen metabolism, including UDP-glycosyltransferases (UGT), sulfotransferases (SULT), CYP3A, and estrogen-related genes. There is some evidence, although controversial, suggesting that select variants may confer risk to certain subtypes of prostate cancer. The most notable finding in 2007 is the highly reproducible link between the chromosome 8q24 risk region and prostate cancer susceptibility. Summary Besides the link between the 8q24 region and prostate cancer risk, population studies do not convincingly show that polymorphisms in androgen metabolism genes are associated with prostate cancer risk. Large epidemiologic studies with comprehensive gene coverage and reliable exposure data are needed to clarify further the role of androgens and their related genes in prostate cancer. C1 [Chu, Lisa W.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chu, Lisa W.] NCI, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Reichardt, Juergen K. V.] Univ Sydney, Plunkett Chair Mol Biol Med, Camperdown, NSW, Australia. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 5024,MSC 7234,6120 Execut Blvd, Bethesda, MD 20892 USA. EM hsinga@mail.nih.gov OI Reichardt, Juergen/0000-0001-6458-2773 FU NCI [P01 CA108964, 1]; NIH, National Cancer Institute FX The authors thank Ms. Sabah Quraishi for her expert help in compiling data and tables for the review and Dr B.J. Stone for editorial assistance. This work was supported in part by NCI grant P01 CA108964 (project 1) to J.K.V.R. who is also a Medical Foundation Fellow at the University of Sydney. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 81 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2008 VL 15 IS 3 BP 261 EP 270 DI 10.1097/MED.0b013e3282febcf6 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V14ST UT WOS:000207754800008 PM 18438175 ER PT J AU Spolski, R Leonard, WJ AF Spolski, Rosanne Leonard, Warren J. TI The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID FOLLICULAR-HELPER-CELLS; T-CELLS; B-CELLS; RHEUMATOID-ARTHRITIS; TH1 CELLS; IL-21; RECEPTOR; DIFFERENTIATION; ACTIVATION; GENERATION AB IL-21 is a type I cytokine that like IL-2, IL-4, IL-7, IL-9, and IL-15 shares the common cytokine receptor gamma chain, gamma(c). IL-21 is produced by activated CD4(+) T cells, NKT cells, and Th17 cells and has pleiotropic actions on a range of lymphoid lineages. IL-21 regulates immunoglobulin production and drives B cell terminal differentiation into plasma cells, cooperatively expands CD8(+) T cells and drives Th17 differentiation, has inhibitory effects on antigen presentation by dendritic cells, and can be pro-apoptotic for B and NK cells. Moreover, IL-21 has potent anti-tumor effects and is implicated in the development of autoimmune diseases. Regulating IL-21 actions in vivo therefore has clinical potential for a range of diseases and is an area of active investigation. C1 [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Spolski, R (reprint author), NHLBI, Lab Mol Immunol, Bldg 10,Rm 7B05, Bethesda, MD 20892 USA. EM spolskirj@nhlbi.nih.gov; wjl@helix.nih.gov FU Intramural NIH HHS [Z01 HL005401-16, Z99 HL999999] NR 50 TC 83 Z9 98 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2008 VL 20 IS 3 BP 295 EP 301 DI 10.1016/j.coi.2008.02.004 PG 7 WC Immunology SC Immunology GA 326JQ UT WOS:000257655200008 PM 18554883 ER PT J AU Bryceson, YT Long, EO AF Bryceson, Yenan T. Long, Eric O. TI Line of attack: NK cell specificity and integration of signals SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; IFN-GAMMA PRODUCTION; IMMUNOLOGICAL SYNAPSE; CUTTING EDGE; INHIBITORY RECEPTORS; CLASS-I; GRANULE POLARIZATION; ACTIVATING RECEPTOR; CYTOKINE SECRETION AB Natural killer (NK) cells possess potent cytolytic activity and secrete immune modulating cytokines. The large repertoire of NK cell receptors provides versatility for the identification of infected and transformed cells and for their elimination by INK cells. NK cell responses also stimulate and regulate the adaptive arm of the immune system. We review current knowledge about the molecular specificity of NK cell receptors and about the regulation of NK cell effector functions upon encounter with target cells. Mechanisms of recognition, interplay among receptors, signal integration, and the dynamic fine-tuning of NK cell responses are discussed. New insights into the molecular checkpoints for NK cell effector function are highlighted, and underlying reasons for the complexity in NK cell recognition and signaling are proposed. C1 [Bryceson, Yenan T.; Long, Eric O.] NIAID, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA. [Bryceson, Yenan T.] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Med,Ctr Infect Med, S-14186 Huddinge, Sweden. RP Bryceson, YT (reprint author), NIAID, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA. EM YBryceson@gmail.com; eLong@nih.gov RI Long, Eric/G-5475-2011; OI Long, Eric/0000-0002-7793-3728; Bryceson, Yenan/0000-0002-7783-9934 FU Intramural NIH HHS [Z01 AI000842-09] NR 81 TC 120 Z9 121 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2008 VL 20 IS 3 BP 344 EP 352 DI 10.1016/j.coi.2008.03.005 PG 9 WC Immunology SC Immunology GA 326JQ UT WOS:000257655200016 PM 18439809 ER PT J AU Rochman, Y Leonard, WJ AF Rochman, Yrina Leonard, Warren J. TI Thymic stromal lymphopoietin: a new cytokine in asthma SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID AIRWAY EPITHELIAL-CELLS; MEDIATED SIGNAL-TRANSDUCTION; CD4(+) T-CELLS; INTERLEUKIN-7 RECEPTOR; ATOPIC-DERMATITIS; ALLERGIC-ASTHMA; IL-4 RECEPTOR; GROWTH-FACTOR; CUTTING EDGE; MAST-CELL AB Airway epithelial cells provide mechanical and immune protection against pathogens and allergens. Following activation, these cells produce a wide range of cytokines including thymic stromal lymphopoietin (TSLP). Recently it was established that a high level of TSLP is associated with asthma in mice and in humans. These findings suggest that interfering with the ability of cells to respond to TSLP might prevent the development of airway inflammation. Our review presents current knowledge on mediators that induce TSLP production and on the actions of TSLP on different populations of cells that are related to airway inflammation. TSLP affects dendritic cells, T cells, NKT cells, and mast cells, indicative of the broad role of TSLP in the regulation of inflammatory/allergic processes. C1 [Rochman, Yrina; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7B05, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Intramural NIH HHS [Z01 HL005401-16, Z99 HL999999] NR 49 TC 41 Z9 44 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD JUN PY 2008 VL 8 IS 3 BP 249 EP 254 DI 10.1016/j.coph.2008.03.002 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 318VI UT WOS:000257120500005 PM 18450510 ER PT J AU Rosenberg, HF AF Rosenberg, H. F. TI Eosinophil-derived neurotoxin/RNase 2: Connecting the past, the present and the future SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE inflammation; ribonuclease; toll-like receptor; dendritic cell; leukocyte ID RESPIRATORY SYNCYTIAL VIRUS; RIBONUCLEASE-A SUPERFAMILY; AMINO-ACID SEQUENCE; CATIONIC PROTEIN; GENE FAMILY; COMPARATIVE TOXICITY; IMMUNE-RESPONSES; GRANULE PROTEINS; RAPID EVOLUTION; DENDRITIC CELLS AB The eosinophil-derived neurotoxin (EDN, also known as eosinophil protein-X) is best-known as one of the four major proteins found in the large specific granules of human eosinophilic leukocytes. Although it was named for its discovery and initial characterization as a neurotoxin, it is also expressed constitutively in human liver tissue and its expression can be induced in macrophages by proinflammatory stimuli. EDN and its divergent orthologs in rodents have ribonuclease activity, and are members of the extensive RNase A superfamily, although the relationship between the characterized physiologic functions and enzymatic activity remains poorly understood. Recent explorations into potential physiologic functions for EDN have provided us with some insights into its role in antiviral host defense, as a chemoattractant for human dendritic cells, and most recently, as an endogenous ligand for toll-like receptor (TLR)2. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000941-04, Z01 AI000942-04, Z01 AI000943-04, Z99 AI999999] NR 49 TC 33 Z9 37 U1 0 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 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD JUN PY 2008 VL 9 IS 3 BP 135 EP 140 DI 10.2174/138920108784567236 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 311RS UT WOS:000256617900002 PM 18673278 ER PT J AU Rybak, SM AF Rybak, S. M. TI Antibody-onconase conjugates: Cytotoxicity and intracellular routing SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE ribonuclease; RNase A; onconase; antibody; immunotoxin; internalization ID B-CELL LYMPHOMA; COMBINED IMMUNODEFICIENT MICE; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; TUMOR-CELLS; ANTITUMOR RIBONUCLEASE; CD22-RECOMBINANT RICIN; MULTIDRUG-RESISTANCE; EPITOPE SPECIFICITY; PROTEIN-SYNTHESIS AB Onconase, a member of the pancreatic ribonuclease A superfamily, is currently in Phase III clinical trials for treatment of unresectable malignant mesothelioma. The anticancer effect of onconase may relate to its intracellular target, a non-coding RNA. Some non-coding RNAs are aberrantly expressed in cancer cells. This discovery is creating new interest in drugs that target RNA. Conjugating onconase to agents that recognize tumor associated molecules further increases its potency and specificity. Analysis of onconase activity when directed to two different internalizing and one non-internalizing receptor reveals that the ideal targeting agents would rapidly enter lysosomal compartments before onconase escaped to the cytosol. Antibody-onconase conjugates are effective in preclinical models, cause little non-specific toxicities in mice and have favorable formulation properties. Understanding the reason for their potency coupled with understanding novel RNA-based mechanisms of tumor cell death will lead to improved variations of targeted onconase. C1 [Rybak, S. M.] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Rybak, SM (reprint author), Bionanomics LLC, 411 Walnut St, Green Cove Springs, FL 32043 USA. EM rybak@mindspring.com NR 51 TC 14 Z9 14 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD JUN PY 2008 VL 9 IS 3 BP 226 EP 230 DI 10.2174/138920108784567272 PG 5 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 311RS UT WOS:000256617900012 PM 18673288 ER PT J AU Kapoor, V Karpov, V Linton, C Subach, FV Verkhusha, VV Telford, WG AF Kapoor, Veena Karpov, Vladimir Linton, Claudette Subach, Fedor V. Verkhusha, Vladislav V. Telford, William G. TI Solid state yellow and orange lasers for flow cytometry SO CYTOMETRY PART A LA English DT Article DE yellow laser; orange laser; diode pumped solid state; red fluorescent protein; Texas Red; allophycocyanin; HcRed; Katushka ID RED FLUORESCENT PROTEIN; DIODES; SENSITIVITY AB Diode and DPSS lasers emitting a variety of wavelengths are now commonly incorporated into flow cytometers, greatly increasing our capacity to excite a wide variety of fluorochromes. Until recently, however, virtually no practical technology existed for generating yellow or orange laser light for flow cytometry that was compatible with smaller instrumentation. In this study, we evaluate several new solid state laser systems that emit from the 570 to 600 nm as excitation sources for flow cytometry. DPSS 580, 589, and 592 nm sources were integrated into a cuvette-based flow cytometer (BD LSR II) and a stream-in-air cell sorter (FACSVantage DiVa), and used to excite a variety of yellow, orange, and red excited fluorochromes, including Texas Red, APC, and its tandem conjugates, and the genetically encoded red fluorescent protein HcRed and the more recently developed Katushka. All laser sources were successfully incorporated into the indicated flow cytometry platforms. The yellow and orange sources (particularly 592 nm) were ideal for exciting Texas Red, and provided excitation of APC and its tandems that was comparable to a traditional red laser source, albeit at higher power levels than red sources. Yellow and orange laser light was optimal for exciting HcRed and Katushka. Practical yellow and orange laser sources are now available for flow cytometry. This technology fills an important gap in the laser wavelengths available for flow, now almost any fluorochrome requiring visible light excitation can be accommodated. Published 2008 Wiley-Liss, Inc. C1 [Kapoor, Veena; Telford, William G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Karpov, Vladimir; Linton, Claudette] MPB Commun, Montreal, PQ, Canada. [Subach, Fedor V.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. RP Telford, WG (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 3-3297,9000 Rockville Pike, Bethesda, MD 20892 USA. EM telfordw@mail.nih.gov RI Subach, Fedor/K-7080-2014 FU NIGMS NIH HHS [R01 GM070358, GM070358, R01 GM073913, GM073913] NR 15 TC 25 Z9 25 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JUN PY 2008 VL 73A IS 6 BP 570 EP 577 DI 10.1002/cyto.a.20563 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309VP UT WOS:000256488600014 PM 18449918 ER PT J AU Mak, KK Kronenberg, HM Chuang, PT Mackem, S Yang, YZ AF Mak, Kinglun Kingston Kronenberg, Henry M. Chuang, Pao-Tien Mackem, Susan Yang, Yingzi TI Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy SO DEVELOPMENT LA English DT Article DE Ihh; patched 1; cartilage; PTHrP; chondrocyte hypertrophy ID HORMONE-RELATED-PROTEIN; GROWTH-PLATE; CARTILAGE DEVELOPMENT; ENDOCHONDRAL BONE; DIFFERENTIATION; IHH; PATHWAYS; PROLIFERATION; OSTEOBLAST; SKELETON AB Chondrocyte hypertrophy is an essential process required for endochondral bone formation. Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by controlling PTHrP expression. To understand whether there is a PTHrP-independent role of Ihh signaling in regulating chondrocyte hypertrophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondral skeletal development. We found that upregulating Ihh signaling in the developing cartilage by treating PTHrP(-/-) limb explants with sonic hedgehog (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP(-/-) embryos or inactivating patched 1 (Ptch1), a negative regulator of hedgehog (Hh) signaling, accelerated chondrocyte hypertrophy in the PTHrP(-/-) embryos. Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened (Smo), a positive regulator of Hh signaling, chondrocyte hypertrophy was delayed in the PTHrP(-/-) embryo. Furthermore, we show that upregulated Hh signaling in the postnatal cartilage led to accelerated chondrocyte hypertrophy during secondary ossification, which in turn caused reduction of joint cartilage. Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy independently of PTHrP, which is particularly important in postnatal cartilage development and homeostasis. In addition, we found that bone morphogenetic protein (Bmp) and Wnt/beta-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy. C1 [Mak, Kinglun Kingston; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chuang, Pao-Tien] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. [Mackem, Susan] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, 49 Covent Dr,MSC 4472, Bethesda, MD 20892 USA. EM yingzi@mail.nih.gov FU NHLBI NIH HHS [HL66600, HL67822]; NIDDK NIH HHS [DK56246] NR 27 TC 111 Z9 126 U1 1 U2 14 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 JUN 1 PY 2008 VL 135 IS 11 BP 1947 EP 1956 DI 10.1242/dev.018044 PG 10 WC Developmental Biology SC Developmental Biology GA 299HW UT WOS:000255747700006 PM 18434416 ER PT J AU Im, YJ Hurley, JH AF Im, Young Jun Hurley, James H. TI Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex SO DEVELOPMENTAL CELL LA English DT Article ID LATE-BUDDING DOMAINS; UBIQUITIN RECOGNITION; MULTIVESICULAR BODY; TRAFFICKING COMPLEX; EAP45-GLUE DOMAIN; RILP INTERACTS; GROWTH-FACTOR; GLUE DOMAIN; PROTEINS; COMPONENT AB ESCRT-II plays a pivotal role in receptor downregulation and multivesicular body biogenesis and is conserved from yeast to humans. The crystal structures of two human ESCRT-II complex structures have been determined at 2.6 and 2.9 angstrom resolution, respectively. The complex has three lobes and contains one copy each of VPS22 and VPS36 and two copies of VPS25. The structure reveals a dynamic helical domain to which both the VPS22 and VPS36 subunits contribute that connects the GLUE domain to the rest of the ESCRT-II core. Hydrodynamic analysis shows that intact ESCRT-II has a compact, closed conformation. ESCRT-II binds to the ESCRT-I VPS28 C-terminal domain subunit through a helix immediately C-terminal to the VPS36-GLUE domain. ESCRT-II is targeted to endosomal membranes by the lipid-binding activities of both the Vps36 GLUE domain and the first helix of Vps22. These data provide a unifying structural and functional framework for the ESCRT-II complex. C1 [Im, Young Jun; Hurley, James H.] NIDDK, Mol Biol Lab, Natl Inst Hlth, US Dept HHS, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, Natl Inst Hlth, US Dept HHS, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov FU Intramural NIH HHS [Z01 DK036123-01] NR 44 TC 47 Z9 53 U1 3 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2008 VL 14 IS 6 BP 902 EP 913 DI 10.1016/j.devcel.2008.04.004 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 312EP UT WOS:000256652200012 PM 18539118 ER PT J AU Toyama, R Rebbert, ML Dey, A Ozato, K Dawid, IB AF Toyama, Reiko Rebbert, Martha L. Dey, Anup Ozato, Keiko Dawid, Igor B. TI Brd4 associates with mitotic chromosomes throughout early zebrafish embryogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE bromodomain; midblastula transition; Brd4; zebrafish; Xenopus; acetylated histones; chromosomes ID BROMODOMAIN PROTEIN BRD4; MAJOR DEVELOPMENTAL TRANSITION; EARLY XENOPUS-EMBRYOS; EFFECT HOMEOTIC GENE; MIDBLASTULA-TRANSITION; P-TEFB; ACETYLATED CHROMATIN; DROSOPHILA-FSH; TRANSCRIPTION; EXPRESSION AB Brd4 is a member of the BET (bromodomains and extraterminal) subfamily of bromodomain proteins that includes chromatin-modifying proteins and transcriptional regulators. Brd4 has a role in cell cycle progression, making it indispensable in mouse embryos and cultured cells. The N-terminal domain of Brd4 participates in a fusion oncogene. Brd4 associates with acetylated histones in chromatin, and this association persists during mitosis implicating Brd4 in epigenetic memory. Brd4 sequence, particularly the bromodomains and ET domain, is conserved in the zebrafish and Xenopus laevis proteins reported here. Brd4 is expressed and localized on mitotic chromosomes in early zebrafish embryos before and after the midblastula transition (MBT), indicating that the Brd4-chromosome association is a conserved property that is maintained even before zygotic transcription. The association of Brd4 with acetylated histones may also be conserved in early embryos as we found that histones H3 and H4 are already acetylated during pre-MBT stages. C1 [Toyama, Reiko; Rebbert, Martha L.; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA. [Dey, Anup; Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mol Growth Regulat, NIH, Bethesda, MD USA. RP Toyama, R (reprint author), Bldg 6B,Room 420,9000 Rockville Pike, Bethesda, MD 20852 USA. EM toyamar@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 44 TC 10 Z9 13 U1 1 U2 1 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 JUN PY 2008 VL 237 IS 6 BP 1636 EP 1644 DI 10.1002/dvdy.21576 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 312EQ UT WOS:000256652300010 PM 18498094 ER PT J AU Liu, IH Zhang, CJ Kim, MJ Cole, GJ AF Liu, I-Hsuan Zhang, Chengjin Kim, Min Jung Cole, Gregory J. TI Retina development in zebrafish requires the heparan sulfate proteoglycan agrin SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE agrin; Fgf; zebrafish; retinotectal; Pax 6; heparan sulfate proteoglycan ID FIBROBLAST-GROWTH-FACTOR; HIPPOCAMPAL-NEURONS; NEURITE OUTGROWTH; RETINOTECTAL PROJECTION; EXTRACELLULAR-MATRIX; HINDBRAIN BOUNDARY; GRADIENT FORMATION; BASEMENT-MEMBRANE; SYNAPSE FORMATION; SIGNALING CENTER AB Recent studies from our laboratory have begun to elucidate the role of agrin in zebrafish development. One agrin morphant phenotype that results from agrin knockdown is microphthalmia (reduced eye size). To begin to understand the mechanisms underlying the role of agrin in eye development, we have analyzed retina development in agrin morphants. Retinal differentiation is impaired in agrin morphants, with retinal lamination being disrupted following agrin morpholino treatment. Pax 6.1 and Mbx1 gene expression, markers of eye development, are markedly reduced in agrin morphants. Formation of the optic fiber layer of the zebrafish retina is also impaired, exhibited as both reduced size of the optic fiber layer, and disruption of retinal ganglion cell axon growth to the optic tectum. The retinotectal topographic projection to the optic tectum is perturbed in agrin morphants in association with a marked loss of heparan sulfate expression in the retinotectal pathway, with this phenotype resembling retinotectal phenotypes observed in mutant zebrafish lacking enzymes for heparan sulfate synthesis. Treatment of agrin morphants with a fibroblast growth factor (Fgf) receptor inhibitor, rescue of the retinal lamination phenotype by transplantation of Fgf8-coated beads, and disruption of both the expression of Fgf-dependent genes and activation of ERK in agrin morphants provides evidence that agrin modulation of Fgf function contributes to retina development. Collectively, these agrin morphant phenotypes provide support for a crucial role of agrin in retina development and formation of an ordered retinotectal topographic map in the optic tectum of zebrafish. (C) 2008 Wiley Periodicals, Inc. C1 [Liu, I-Hsuan; Zhang, Chengjin; Cole, Gregory J.] Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. [Kim, Min Jung] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Cole, Gregory J.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. RP Cole, GJ (reprint author), Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. EM gcole@nccu.edu RI Liu, I-Hsuan/D-9043-2017 OI Liu, I-Hsuan/0000-0002-4524-3263 FU NCRR NIH HHS [RR12546]; NINDS NIH HHS [NS33981] NR 97 TC 11 Z9 11 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD JUN PY 2008 VL 68 IS 7 BP 877 EP 898 DI 10.1002/dneu.20625 PG 22 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 311PG UT WOS:000256611500003 PM 18327763 ER PT J AU Qiu, CX Cotch, MF Sigurdsson, S Garcia, M Klein, R Jonasson, F Klein, BEK Eiriksdottir, G Harris, TB van Buchem, MA Gudnason, V Lanner, LJ AF Qiu, Chengxuan Cotch, Mary Frances Sigurdsson, Sigurdur Garcia, Melissa Klein, Ronald Jonasson, Fridbert Klein, Barbara E. K. Eiriksdottir, Gudny Harris, Tamara B. van Buchem, Mark A. Gudnason, Vilmundur Lanner, Lenore J. TI Retinal and cerebral microvascular signs and diabetes - The age, Gene/Environment Susceptibility-Reykjavik Study SO DIABETES LA English DT Article ID WHITE-MATTER LESIONS; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; AMYLOID ANGIOPATHY; BLOOD-PRESSURE; INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; OLDER PERSONS; ABNORMALITIES AB OBJECTIVE-Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. RESEARCH DESIGN AND METHODS-The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral micro-bleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. RESULTS-Evidence of brain microbleeds was found in 485 (11.5%) people, including 192 with multiple ( >= 2) microbleeds. Subjects with signs of retinal microvascular lesions were at a significantly increased likelihood for having multiple CMBs, People with diabetes in combination with the presence of either retinal AV nicking (odds ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28 [1.24-4.18]) were significantly more likely to have multiple CMBs. CONCLUSIONS-Retinal microvascular abnormalities and brain microbleeds may occur together in older adults. People with both diabetes and signs of retinal microvascular lesions (AV nicking and microaneurysms/hemorrhages) are more likely to have multiple microbleeds in the brain. Microvascular disease in diabetes extends to the brain. C1 [Qiu, Chengxuan; Garcia, Melissa; Harris, Tamara B.; Lanner, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol, Sch Med & Publ Hlth, Madison, WI USA. [Jonasson, Fridbert; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Jonasson, Fridbert] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland. [van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. RP Lanner, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Qiu, Chengxuan/0000-0003-1922-4912; Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU Intramural NIH HHS [Z01 EY000401-07, Z99 EY999999, Z01 EY000401-06, ZIA EY000401-08, ZIA EY000401-09, ZIA EY000401-10]; NIA NIH HHS [N01-AG-1-2100] NR 40 TC 43 Z9 47 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 JUN PY 2008 VL 57 IS 6 BP 1645 EP 1650 DI 10.2337/db07-1455 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 311PH UT WOS:000256611600026 PM 18332097 ER PT J AU Liu, XB Mameza, MG Lee, YS Eseonu, CI Yu, CR Derwent, JJK Egwuagu, CE AF Liu, Xuebin Mameza, Marie G. Lee, Yun Sang Eseonu, Chikezie I. Yu, Cheng-Rong Derwent, Jennifer J. Kang Egwuagu, Charles E. TI Suppressors of cytokine-signaling proteins induce insulin resistance in the retina and promote survival of retinal cells SO DIABETES LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEITIS; PIGMENT EPITHELIAL-CELLS; DIABETIC-RETINOPATHY; METABOLIC SYNDROME; HEPATIC STEATOSIS; INTERFERON-GAMMA; SOCS PROTEINS; RAT RETINA; IN-VIVO; EXPRESSION AB OBJECTIVE-Suppressors of cytokine signaling (SOCS) are implicated in the etiology of diabetes, obesity, and metabolic syndrome. Here, we show that some SOCS members are induced, while others are constitutively expressed, in retina and examine whether persistent elevation of SOCS levels in retina by chronic inflammation or cellular stress predisposes to developing insulin resistance in retina, a condition implicated in diabetic retinopathy. RESEARCH DESIGN AND METHODS-SOCS-mediated insulin resistance and neuroprotection in retina were investigated in 1) an experimental uveitis model, 2) SOCS1 transgenic rats, 3) insulin-deficient diabetic rats, 4) retinal cells depleted of SOCS6 or overexpressing SOCS1/SOCS3, and 5) oxidative stress and light-induced retinal degeneration models. RESULTS-We show that constitutive expression of SOCS6 protein in retinal neurons may improve glucose metabolism, while elevated SOCS1/SOCS3 expression during uveitis induces insulin resistance in neuroretina. SOCS-mediated insulin resistance, as indicated by its inhibition of basally active phosphomositide 3-kinase/AKT signaling in retina, is validated in retina-specific SOCS1 transgenic rats and retinal cells overexpressmig SOCS1/SOCS3. We further show that the SOCS3 level is elevated in retina by oxidative stress, metabolic stress of insulin-deficient diabetes, or light-induced retinal damage and protects ganglion cells from apoptosis, suggesting that upregulation of SOCS3 may be a common physiologic response of neuroretinal cells to cellular stress. CONCLUSIONS-Our data suggest two-sided roles of SOCS proteins in retina. Whereas SOCS proteins may improve glucose metabolism, mitigate deleterious effects of inflammation, and promote neuroprotection, persistent SOCS3 expression caused by chronic inflammation or cellular stress can induce insulin resistance and inhibit neurotrophic factors, such as ciliary neurotrophic factor, leukemia inhibitory factor, and insulin, that are essential for retinal cell survival. C1 [Liu, Xuebin; Mameza, Marie G.; Lee, Yun Sang; Eseonu, Chikezie I.; Yu, Cheng-Rong; Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Eseonu, Chikezie I.] Harvard Univ, Dept Biomed Engn, Harvard Coll, Cambridge, MA 02138 USA. [Derwent, Jennifer J. Kang] IIT, Pritzker Inst Biomed Sci & Engn, Dept Biomed Engn, Chicago, IL 60616 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Rm 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000280-16] NR 47 TC 28 Z9 32 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 JUN PY 2008 VL 57 IS 6 BP 1651 EP 1658 DI 10.2337/db07-1761 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 311PH UT WOS:000256611600027 PM 18356406 ER PT J AU Abati, A AF Abati, Andrea TI The National Cancer Institute thyroid FNA State of the Science Conference: "Wrapped Up" SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material ID NODULES C1 NCI, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM abatia@mail.nih.gov NR 14 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2008 VL 36 IS 6 BP 388 EP 389 DI 10.1002/dc.20850 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 312EN UT WOS:000256652000007 PM 18478606 ER PT J AU Baloch, ZW LiVolsi, VA Asa, SL Rosai, J Merino, MJ Randolph, G Vielh, P DeMay, RM Sidawy, MK Frable, WJ AF Baloch, Zubair W. LiVolsi, Virginia A. Asa, Syl L. Rosai, Juan Merino, Maria J. Randolph, Gregory Vielh, Philippe DeMay, Richard M. Sidawy, Mary K. Frable, William J. TI Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: A Synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiration State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst DE thyroid; fine-needle aspiration; classification scheme; morphologic features ID TALL CELL VARIANT; INTRANUCLEAR CYTOPLASMIC INCLUSIONS; HISTOLOGIC FOLLOW-UP; HURTHLE-CELL; PAPILLARY CARCINOMA; FOLLICULAR VARIANT; GRAVES-DISEASE; HASHIMOTOS-THYROIDITIS; FROZEN-SECTION; MICROFOLLICULAR NODULE AB The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The two-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May I and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding diagnostic terminology/classification scheme for thyroid FNA interpretation and cytomorphologic criteria for the diagnosis of various benign and malignant thyroid lesions. C1 [Baloch, Zubair W.; LiVolsi, Virginia A.] Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. [LiVolsi, Virginia A.] Univ Penn, Med Ctr, Dept Otorhinolaryngol & Surg, Philadelphia, PA 19104 USA. [Asa, Syl L.] Univ Toronto, Univ Hlth Network, Dept Pathol & Lab Med, Toronto, ON, Canada. [Rosai, Juan] CDI, Ctr Consulenze Anat Patol Oncol, Dept Pathol, Milan, Italy. [Merino, Maria J.] NCI, Dept Surg Pathol, Bethesda, MD 20892 USA. [Randolph, Gregory] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [DeMay, Richard M.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Sidawy, Mary K.] Georgetown Univ, Dept Pathol, Washington, DC USA. [Frable, William J.] Virginia Commonwealth Univ, Med Ctr, Dept Pathol, Richmond, VA USA. RP Baloch, ZW (reprint author), Univ Penn, Med Ctr, Dept Pathol, 6 Founders Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM baloch@mail.med.upenn.edu NR 162 TC 371 Z9 392 U1 2 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2008 VL 36 IS 6 BP 425 EP 437 DI 10.1002/dc.20830 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 312EN UT WOS:000256652000011 PM 18478609 ER PT J AU Filie, AC Asa, SL Geisinger, KR Logani, S Merino, M Nikiforov, YE Clark, DR AF Filie, Armando C. Asa, Sylvia L. Geisinger, Kim R. Logani, Sanjay Merino, Maria Nikiforov, Yuri E. Clark, Douglas R. TI Utilization of ancillary studies in thyroid Fine Needle Aspirates: A Synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiratin State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst DE thyroid; fine needle aspiration; ancillary studies; immunohistochemistry; flow cytometry; molecular studies ID TRANSCRIPTION FACTOR-I; MONOCLONAL-ANTIBODIES; CARCINOEMBRYONIC ANTIGEN; ANAPLASTIC CARCINOMA; MEDULLARY CARCINOMA; THYROGLOBULIN; EXPRESSION; DIAGNOSIS; NODULES; TUMORS AB The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May I and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding the utilization of ancillary studies in thyroid FNA. C1 [Filie, Armando C.; Merino, Maria] NCI, Cytopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [Asa, Sylvia L.] Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [Asa, Sylvia L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Geisinger, Kim R.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27103 USA. [Logani, Sanjay] Emory Univ Hosp, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Nikiforov, Yuri E.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Clark, Douglas R.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Filie, AC (reprint author), NCI, Cytopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. EM afilie@mail.nih.gov NR 24 TC 41 Z9 42 U1 0 U2 4 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 JUN PY 2008 VL 36 IS 6 BP 438 EP 441 DI 10.1002/dc.20831 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 312EN UT WOS:000256652000012 PM 18478603 ER PT J AU Layfield, LJ Abrams, J Cochand-Priollet, B Evans, D Gharib, H Greenspan, F Henry, M LiVolsi, V Merino, M Michael, CW Wang, H Wells, SA AF Layfield, Lester J. Abrams, Jacki Cochand-Priollet, Beatrix Evans, Doug Gharib, Hossein Greenspan, Frank Henry, Michael LiVolsi, Virginia Merino, Maria Michael, Claire W. Wang, Helen Wells, Samuel A. TI Post-thyroid FNA testing and treatment options: A Synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiration State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst DE thyroid; fine-needle aspiration; follow-up; ultrasound; nondiagnostic; indeterminate; follicular neoplasm; papillary carcinoma ID SUPPRESSIVE THERAPY; DOUBLE-BLIND; NODULES; BIOPSY; FEATURES; DISEASE; ULTRASONOGRAPHY; LEVOTHYROXINE; ULTRASOUND; MALIGNANCY AB The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference oil October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational Web site and several on-line discussion periods between May I and December 15, 2007 (http://thyroidfna.cancer.gov). This document addresses follow-up procedures and therapeutic options for suggested diagnostic categories. Follow-lip options for "nondiagnostic" and "benign" thyroid aspirates are given. The value of ultrasound examination in the follow-up of "nondiagnostic" and "benign" thyroid aspirates is discussed. Ultrasound findings requiring reaspiration or surgical resection are described as are the tinting and length of clinical and ultrasonographic surveillance for cytologically "benign" nodules. Options for surgical intervention are given for the diagnostic categories of "atypicall borderline," 'follicular neoplasm," "suspicious for malignancy" and "malignant". C1 [Layfield, Lester J.] Univ Utah Hosp & Clin, Dept Pathol, Huntsman Canc Ctr, Salt Lake City, UT 84112 USA. [Abrams, Jacki] Clin Pathol Associates, Dept Pathol, Austin, TX USA. [Cochand-Priollet, Beatrix] Univ Paris 07, Lariboisiere Hosp, Dept Pathol, Paris, France. [Evans, Doug] Univ Texas MD Anderson Canc Ctr, Dept Pancreat Endocrinol, Houston, TX 77030 USA. [Gharib, Hossein] Mayo Clin, Dept Endocrinol, Rochester, MN USA. [Greenspan, Frank] Univ Calif San Francisco, Med Ctr, Dept Endocrinol, San Francisco, CA 94143 USA. [Henry, Michael] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [LiVolsi, Virginia] Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Merino, Maria] Natl Inst Hlth, Ctr Clin, Bethesda, MA USA. [Michael, Claire W.] Univ Michigan Hosp, Dept Pathol, Ann Arbor, MI 48109 USA. [Wang, Helen] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Wells, Samuel A.] Washington Univ, Med Ctr, Dept Surg, St Louis, MO USA. RP Layfield, LJ (reprint author), Univ Utah Hosp & Clin, Dept Pathol, Huntsman Canc Ctr, 1950 Circle Hope,Room 3860, Salt Lake City, UT 84112 USA. EM layfiel@aruplab.com NR 36 TC 60 Z9 62 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2008 VL 36 IS 6 BP 442 EP 448 DI 10.1002/dc.20832 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 312EN UT WOS:000256652000013 PM 18478610 ER PT J AU Eum, SY Lee, YJ Kwak, HK Min, JH Hwang, SH Via, LE Barry, CE Cho, SN AF Eum, Seok-Yong Lee, Ye-Jin Kwak, Hyun-Kyung Min, Jin-Hong Hwang, Soo Hee Via, Laura E. Barry, Clifton E., III Cho, Sang-Nae TI Evaluation of the diagnostic utility of a whole-blood interferon-gamma assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE tuberculosis; latent infection; IFN-gamma;; "QuantiFERON (R)-TB Gold In-Tube" ID T-CELL RESPONSES; SKIN-TEST; NORTHERN MALAWI; HIV EPIDEMIC; RURAL INDIA; IFN-GAMMA; INFECTION; VACCINATION; CHILDREN; BURDEN AB We evaluated the utility of the "QuantiFERON(R)-TB Gold In-Tube" (QuatitiFERON(R)) test that uses tuberculosis (TB)-specific antigens for the diagnosis of latent infection in such individuals. We also examined the correlation between the interferon (IFN)-gamma response to these antigens and the exposure risk to TB by evaluating antigen-specific IFN-gamma release in comparison with IFN-gamma release in response to purified protein derivative (PPD) in 3 groups: medical students, nurses in a TB hospital, and TB patients. All nurses and TB patients responded to PPD, whereas 52% (P < 0.0001) and 79.2% (P = 0.04) responded to QuantiFERON(R), respectively. In the medical students, only 10.4% responded to QuantiFERON(R), whereas 85.2% were positive to PPD (P < 0.0001). There was also a significant correlation between the levels of IFN-gamma production and the duration of employment in the group of nurses at the TB hospital, suggesting ongoing exposure in this high-risk group. Thus, these results demonstrate that Mycobacterium tuberculosis-specific IFN-gamma release assay accurately discriminates low- and high-risk healthy subjects and might therefore be a useful diagnostic tool for the diagnosis of latent infection in Bacille Caltrieffe-Guerin (BCG)-vaccitiated individuals. (C) 2008 Elsevier Inc. All rights reserved. C1 [Eum, Seok-Yong; Lee, Ye-Jin; Kwak, Hyun-Kyung] Int TB Res Ctr, Div Immunopathol & Cell Immunol, Masan, South Korea. [Min, Jin-Hong; Hwang, Soo Hee] Yonsei Univ, Coll Med, Natl Masan TB Hosp, Seoul 120752, South Korea. [Eum, Seok-Yong; Cho, Sang-Nae] Yonsei Univ, Coll Med, Dept Microbiol & Brain, Korea Project Med Sci 21, Seoul 120752, South Korea. [Via, Laura E.; Barry, Clifton E., III] NIAID, NIH, TB Res Sect, Bethesda, MD 20892 USA. RP Eum, SY (reprint author), Int TB Res Ctr, Div Immunopathol & Cell Immunol, Masan, South Korea. EM syeumkr@gmail.com RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU Intramural NIH HHS [NIH0011201348, Z01 AI000734-12] NR 31 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUN PY 2008 VL 61 IS 2 BP 181 EP 186 DI 10.1016/j.diagmicrobio.2008.01.002 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 309VX UT WOS:000256489400009 PM 18296002 ER PT J AU Mourra, N Zeitoun, G Portier, G Blanche, H Tubacher, E Gressin, L Flejou, JF Tiret, E Thomas, G Olschwang, S AF Mourra, Najat Zeitoun, Guy Portier, Guillaume Blanche, Helene Tubacher, Emmanuel Gressin, Laetitia Flejou, Jean-Francois Tiret, Emmanuel Thomas, Gilles Olschwang, Sylviane TI High-resolution genotyping of chromosome 8 in colon adenocarcinomas reveals recurrent break point but no gene mutation in the 8p21 region SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE colon neoplasm; chromosome instability; tumor suppressor gene; somatic mutation; genotyping ID TUMOR-SUPPRESSOR GENES; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; CARCINOMAS; MARKERS; GAIN AB The prognosis of patients with colorectal cancer is largely determined by the tumor stage. In this respect, colorectal cancer with lymph node metastases has the worst prognosis. Accordingly, there is considerable clinical interest in understanding the genetic mechanisms underlying metastasis formation. The short arm of chromosome 8 is often lost in colorectal cancer and has been associated with the advanced stages. A common region of deletion has been identified in 8p21, and we investigate here the localization of the putative tumor suppressor gene. A series of 683 sporadic microsatellite stability colorectal tumor samples has been genotyped on 12 microsatellite loci encompassing the common deleted region. Allelic losses were identified in 50% of the cases and 10 break points have been evidenced between D8S1734 and D8S1810, reducing the region of interest to D8S1771-D8S131. Among the 21 genes mapped in this interval, 14 candidate genes have been retained for the sequencing analysis of 48 tumors with 8p allelic loss. No mutation was found, suggesting more complex mechanisms of inactivation or side effects of chromosome arm 8q duplication, which might be up-regulating oncogenes not located within the deleted region. C1 [Olschwang, Sylviane] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Mourra, Najat; Flejou, Jean-Francois; Tiret, Emmanuel] CHU St Antoine, Dept Pathol, St Antoine, France. [Blanche, Helene; Tubacher, Emmanuel; Gressin, Laetitia] Fdn Jean Dausset, Paris, France. [Zeitoun, Guy] Hop Quesnay, Dept Surg, Mantes La Jolie, France. [Portier, Guillaume] CHU Purpan, Dept Surg, Toulouse, France. [Olschwang, Sylviane] INSERM, U599, Ctr Rech Cancerol Marseille, F-75654 Paris 13, France. [Olschwang, Sylviane] Univ Aix Marseille 2, Marseille, France. [Thomas, Gilles] NCI, NIH, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. RP Olschwang, S (reprint author), Inst J Paoli I Calmettes, 232 Blvd St Marguerite, F-13009 Marseille, France. EM olschwangs@marseille.fnclcc.fr RI Olschwang, Sylviane/G-2716-2013 NR 21 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD JUN PY 2008 VL 17 IS 2 BP 90 EP 93 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 307BW UT WOS:000256293700004 PM 18382363 ER PT J AU Neuman, MG Sha, K Esguerra, R Zakhari, S Winkler, RE Hilzenrat, N Wyse, J Cooper, CL Seth, D Gorrell, MD Haber, PS McCaughan, GW Leo, MA Lieber, CS Voiculescu, M Buzatu, E Ionescu, C Dudas, J Saile, B Ramadori, G AF Neuman, Manuela G. Sha, Kevin Esguerra, Rustan Zakhari, Sam Winkler, Robert E. Hilzenrat, Nir Wyse, Jonathan Cooper, Curtis L. Seth, Devanshi Gorrell, Mark D. Haber, Paul S. McCaughan, Geoffrey W. Leo, Maria A. Lieber, Charles S. Voiculescu, Mihai Buzatu, Eugenia Ionescu, Camelia Dudas, Jozsef Saile, Bernhard Ramadori, Giuliano TI Inflammation and repair in viral hepatitis C SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on Cytokines and Chemokines CY SEP 07-09, 2005 CL Montreal, CANADA SP Canadian Inst Hlth Res, Inst Infect & Immun, Natl Inst Alcohol Abuse & Alcoholism, NIH DE hepatitis C; inflammation; fibrosis; cytokines; chemokines; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR-BETA; ALCOHOLIC LIVER-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; T-HELPER-CELLS; RIBAVIRIN COMBINATION THERAPY; INTRAHEPATIC GENE-EXPRESSION; HIV PROTEASE INHIBITORS; INFECTED PATIENTS; INTERFERON-ALPHA AB Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host's immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-alpha,) and ribavirin, about half of individuals infected with some genotypes, for example genotypes I and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications. C1 [Neuman, Manuela G.; Sha, Kevin; Esguerra, Rustan] S Tower MaRS Discovery Ctr, Toronto, ON M5G 1L5, Canada. [Neuman, Manuela G.; Sha, Kevin; Esguerra, Rustan] Univ Toronto, Inst Drug Res, Dept Pharmacol Biophys & Global Hlth, Toronto, ON, Canada. [Neuman, Manuela G.; Sha, Kevin; Esguerra, Rustan] Univ Toronto, Ctr Int Hlth, Toronto, ON, Canada. [Zakhari, Sam] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD USA. [Winkler, Robert E.] Schering Plough Corp, Kenilworth, NJ 07033 USA. [Hilzenrat, Nir; Wyse, Jonathan] McGill Univ, Jewish Gen Hosp, Dept Med, Div Gastroenterol,SMBD, Montreal, PQ H3T 1E2, Canada. [Cooper, Curtis L.] Univ Ottawa Hosp, Div Infect Dis, Ottawa, ON, Canada. [Seth, Devanshi; Haber, Paul S.] Royal Prince Alfred Hosp, Drug Hlth Serv, Camperdown, NSW 2050, Australia. [Seth, Devanshi; Haber, Paul S.] Royal Prince Alfred Hosp, AW Morrow Gastroenterol & Liver Ctr, Camperdown, NSW 2050, Australia. [Seth, Devanshi; Gorrell, Mark D.; Haber, Paul S.; McCaughan, Geoffrey W.] Univ Sydney, Centenary Inst, Sydney, NSW 2006, Australia. [Seth, Devanshi; Gorrell, Mark D.; Haber, Paul S.; McCaughan, Geoffrey W.] Univ Sydney, Discipline Med, Sydney, NSW 2006, Australia. [Leo, Maria A.; Lieber, Charles S.] JJ Peters Vet Adm Hosp, Alcohol Res Ctr, Rdbronx, NY 10468 USA. [Leo, Maria A.; Lieber, Charles S.] Mt Sinai Hosp, Rdbronx, NY 10468 USA. [Voiculescu, Mihai; Buzatu, Eugenia; Ionescu, Camelia] Fundeni Clin Inst, Ctr Internal Med, Bucharest, Romania. [Dudas, Jozsef; Saile, Bernhard; Ramadori, Giuliano] Univ Gottingen, Dept Internal Med, Sect Gastroenterol & Endocrinol, Gottingen, Germany. RP Neuman, MG (reprint author), S Tower MaRS Discovery Ctr, 101 Coll St,South Tower,Suite 300,Lab 351, Toronto, ON M5G 1L5, Canada. EM m_neuman@rogers.com OI Gorrell, Mark/0000-0002-0528-2604 NR 192 TC 24 Z9 25 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2008 VL 53 IS 6 BP 1468 EP 1487 DI 10.1007/s10620-007-0047-3 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302GB UT WOS:000255955700005 PM 17994278 ER PT J AU Martin, RCG Barker, DF Doll, MA Pine, SR Mechanic, L Bowman, ED Harris, CC Hein, DW AF Martin, Robert C. G. Barker, David F. Doll, Mark A. Pine, Sharon R. Mechanic, Leah Bowman, Elise D. Harris, Curtis C. Hein, David W. TI Manganese superoxide dismutase gene coding region polymorphisms lack clinical incidence in general population SO DNA AND CELL BIOLOGY LA English DT Article ID CANCER; PROMOTER; CELLS; SITE AB Two functional polymorphisms within the manganese superoxide dismutase (MnSOD) gene have been reported to lead to increased oxidative stress damage. The MnSOD 58T > C single nucleotide polymorphism(SNP) within exon 3 changes isoleucine to threonine, leading to decreased thermal stability and reduced enzymatic activity in vivo and in vitro. The MnSOD 60C > T polymorphism within exon 3 changes leucine to phenylalanine, rendering the protein sensitive to redox regulation by intracellular thiols. Thus, the goal of this study was to evaluate the 58T > C and 60C > T MnSOD polymorphisms in a large case-control study. Taqman allelic discrimination assays were developed to identify the 58T > C and 60C > T SNPs in exon 3. Two hundred and eight lung cancer cases and 141 controls were evaluated for these two SNPs, and all 349 subjects were of the wild-type homozygous genotype for both 58C and 60T in exon 3. This study suggests that although the 58T > C and 60C > T polymorphisms reduce MnSOD enzymatic activity, these polymorphisms were not identified in the present case-control study population. C1 [Martin, Robert C. G.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Dept Surg, Louisville, KY 40292 USA. [Barker, David F.; Doll, Mark A.; Hein, David W.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Mechanic, Leah; Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Martin, RCG (reprint author), 315 East Broadway,Room 313, Louisville, KY 40202 USA. EM Robert.martin@louisville.edu RI Hein, David/A-9707-2008 FU Intramural NIH HHS [Z01 BC005480-22] NR 17 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 2008 VL 27 IS 6 BP 321 EP 323 DI 10.1089/dna.2007.0725 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 317UQ UT WOS:000257046100004 PM 18466086 ER PT J AU Poltoratsky, V Horton, JK Prasad, R Beard, WA Woodgate, R Wilson, SH AF Poltoratsky, Vladimir Horton, Julie K. Prasad, Rajendra Beard, William A. Woodgate, Roger Wilson, Samuel H. TI Negligible impact of pol iota expression on the alkylation sensitivity of pol beta-deficient mouse fibroblast cells SO DNA REPAIR LA English DT Letter DE pol beta; pol iota; base excision repair; alkylation agent sensitivity; mouse embryonic fibroblasts ID DNA-POLYMERASE-IOTA; BASE EXCISION-REPAIR; LYASE ACTIVITY; SOMATIC HYPERMUTATION; IMMUNOGLOBULIN; MUTAGENESIS; PROTECTS; LAMBDA; DAMAGE; GENES C1 [Poltoratsky, Vladimir; Horton, Julie K.; Prasad, Rajendra; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Woodgate, Roger] NICHD, Lab Genom Instabil, NIH, Bethesda, MD 20892 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050159-11] NR 22 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 1 PY 2008 VL 7 IS 6 BP 830 EP 833 DI 10.1016/j.dnarep.2008.02.013 PG 4 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 317VU UT WOS:000257049200001 PM 18434259 ER PT J AU Brooks, PJ Cheng, TF Cooper, L AF Brooks, P. J. Cheng, Tsu-Fan Cooper, Lori TI Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage? SO DNA REPAIR LA English DT Review DE Aicardi-Goutieres syndrome; Cockayne syndrome; oligodendrocytes; myelin; calcification; vascular disease; thyroid hormone; TREX1; RNASEH2; toll-like receptor; innate immune system ID AICARDI-GOUTIERES-SYNDROME; TELANGIECTASIA-LIKE DISORDER; NUCLEOTIDE EXCISION-REPAIR; FACIO-SKELETAL SYNDROME; DOUBLE-STRAND BREAKS; INNATE IMMUNE RECOGNITION; FAMILIAL CHILBLAIN LUPUS; CENTRAL-NERVOUS-SYSTEM; UV-SENSITIVE SYNDROME; COCKAYNE-SYNDROME AB The classic model for neurodegeneration due to mutations in DNA repair genes holds that DNA damage accumulates in the absence of repair, resulting in the death of neurons. This model was originally put forth to explain the dramatic loss of neurons observed in patients with xeroderma pigmentosum neurologic disease, and is likely to be valid for other neurodegenerative diseases due to mutations in DNA repair genes. However, in trichiothiodystrophy (TTD), Aicardi-Goutieres syndrome (AGS), and Cockayne syndrome (CS), abnormal myelin is the most prominent neuropathological feature. Myelin is synthesized by specific types of glial cells called oligodendrocytes. In this review, we focus on new studies that illustrate two disease mechanisms for myelin defects resulting from mutations in DNA repair genes, both of which are fundamentally different than the classic model described above. First, studies using the TTD mouse model indicate that TFIIH acts as a co-activator for thyroid hormone-dependent gene expression in the brain, and that a causative XPD mutation in TTD results in reduction of this co-activator function and a dysregulation of myelin-related gene expression. Second, in AGS, which is caused by mutations in either TREX1 or RNASEH2, recent evidence indicates that failure to degrade nucleic acids produced during S-phase triggers activation of the innate immune system, resulting in myelin defects and calcification of the brain. Strikingly, both myelin defects and brain calcification are both prominent features of CS neurologic disease. The similar neuropathology in CS and AGS seems unlikely to be due to the loss of a common DNA repair function, and based on the evidence in the literature, we propose that vascular abnormalities may be part of the mechanism that is common to both diseases. In summary, while the classic DNA damage accumulation model is applicable to the neuronal death due to defective DNA repair, the myelination defects and brain calcification seem to be better explained by quite different mechanisms. We discuss the implications of these different disease mechanisms for the rational development of treatments and therapies. Published by Elsevier B.V. C1 [Brooks, P. J.; Cheng, Tsu-Fan; Cooper, Lori] NIAAA, Mol Neurobiol Sect, Neurogenet Lab, Rockville, MD 20852 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, 5625 Fishers Lane,Room 3S32, Rockville, MD 20852 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z01 AA000083-14, Z99 AA999999] NR 104 TC 52 Z9 53 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 1 PY 2008 VL 7 IS 6 BP 834 EP 848 DI 10.1016/j.dnarep.2008.01.017 PG 15 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 317VU UT WOS:000257049200002 PM 18339586 ER PT J AU Rubin, B Gluck, ME Knoll, CM Lorence, M Geliebter, A AF Rubin, B. Gluck, M. E. Knoll, C. M. Lorence, M. Geliebter, A. TI Comparison of eating disorders and body image disturbances between Eastern and Western countries SO EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY LA English DT Article DE Tibet; Eating Attitudes Test (EAT); Figure Rating Scale (FRS); cross-cultural; ethnicity; socio-economic status (SES); body image distortion; media ID ADOLESCENT FEMALES; DIETING BEHAVIOR; ATTITUDES TEST; WEIGHT; WOMEN; SCHOOLGIRLS; POPULATION; DEPRESSION AB Factors associated with the development of eating disorders in countries With non-Western cultures have not been adequately investigated in relation to Westernized countries. We therefore studied 243 girls [age =16.5 +/- 1.2 (SD)], recruited from schools in India, Tibet, the US and France. They completed the Figure Rating Scale (FRS), the Eating Attitudes Test (EAT), and the Beck Depression Inventory (BDI). The Tibetan group had a lower body mass index (BMI) than the other groups (p<0.0001), which did not differ from each other. All groups differed significantly on socio-economic status (SES), with those living in India having the highest (p<0.0001). Prior to controlling for age, SES, and BMI, there were no significant differences on any psychological measure between the individual countries, or when collapsed by East vs. West. However, after controlling for the same covariates, the Tibetan group selected a significantly larger current (p<0.0001) and ideal body size (p=0.03), compared to all the other countries, and had more body image discrepancy than the American group (p=0.04). After controlling only for BMI, the girls from the East had a larger current and ideal, but no difference on body image discrepancy. Body image discrepancy scores were best predicted by EAT scores and BMI, accounting for 35% or the variance (p<0.0001). EAT scores themselves were best predicted by mother's education, BDI, body image discrepancy, and drug and tobacco use, accounting for 33% of the variance (p<0.0001). Unlike some other studies, we did not observe greater body image discrepancy and eating pathology in Western cultures, whether or not controlling for age, SES, and BMI. There were no differences in eating and depression pathology between those in the US, France, or India. Indeed, the Tibetans, after controlling for their low BMI and SES, had the greatest body image discrepancy. C1 [Gluck, M. E.] NIDDK, ODCRS, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. [Rubin, B.; Knoll, C. M.; Lorence, M.; Geliebter, A.] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York Obes Res Ctr,Dept Med, New York, NY USA. [Rubin, B.; Knoll, C. M.; Lorence, M.; Geliebter, A.] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York Obes Res Ctr,Dept Psychiat, New York, NY USA. RP Gluck, ME (reprint author), NIDDK, ODCRS, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St,Room 541, Phoenix, AZ 85016 USA. EM gmarci@mail.nih.gov FU NIDDK NIH HHS [R01 DK074046-02S1, R01 DK074046, R01 DK074046-01A1, R01 DK074046-01A1S1, R01 DK074046-02, R01 DK074046-02S2, R01 DK074046-03, R01 DK074046-04, R01 DK074046-05] NR 35 TC 9 Z9 9 U1 3 U2 19 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1124-4909 J9 EAT WEIGHT DISORD-ST JI Eat. Weight Disord.-Stud. Anorex. PD JUN PY 2008 VL 13 IS 2 BP 73 EP 80 PG 8 WC Psychiatry SC Psychiatry GA 360XO UT WOS:000260091700003 PM 18612255 ER PT J AU Xu, X Othman, EEDR Issaq, HJ Hornung, D Al-Hendy, A Veenstra, TD AF Xu, Xia Othman, Essam El-Dine R. Issaq, Haleem J. Hornung, Daniela Al-Hendy, Ayman Veenstra, Timothy D. TI Multiplexed quantitation of endogenous estrogens and estrogen metabolites in human peritoneal fluid SO ELECTROPHORESIS LA English DT Article DE capillary liquid chromatography; electrospray ionization-tandem mass spectrometry; endogenous estrogens and estrogen metabolites; human peritoneal fluid; selected reaction monitoring ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; MENSTRUAL-CYCLE; WOMEN; DERIVATIZATION; SEPARATION; ORIGIN AB Endogenous estrogens and estrogen metabolites (EM) in human peritoneal fluid may play an important role in health and disease, yet little is known regarding their types and levels present in human peritoneal fluid, primarily due to the lack of an analytical method that is capable of directly quantifying their absolute abundances. In this report, we describe the application of a capillary LC-MS/MS method for identifying and quantifying biologically active and total endogenous EM in human peritoneal fluid. The method requires only 50 mu L of peritoneal fluid, yet can quantify 13 distinct EM. Calibration curves for each EM were linear over a 10(3)-fold concentration range and the lower LOQ was 50 fg on-column. For a charcoal stripped human peritoneal fluid sample containing 10 pg/mL of each EM, accuracy ranged from 83 to 118%, and intrabatch precision ranged from 0.2 to 4.4% RSD and interbatch precision ranged from 5.5 to 15.5% RSD. The analyses of human female peritoneal fluid shows that at least 10 biologically active and 11 total endogenous EM can be positively identified and quantitatively measured. Many of the biologically active forms are present in high abundance and possess distinct biological activities which warrant further study. Although micellar EKC gave baseline separation of a standard mixture of 10 EM, the LOQs using UV detection were not suitable for the assay of the low level estrogens in biological samples. C1 [Xu, Xia; Issaq, Haleem J.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Othman, Essam El-Dine R.; Al-Hendy, Ayman] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA. [Othman, Essam El-Dine R.] Assiut Univ, Dept Obstet & Gynecol, Assiut, Egypt. [Hornung, Daniela] Univ Schleswig Holstein, Dept Obstet & Gynecol, Lubeck, Germany. RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NICHD NIH HHS [R01 HD046228] NR 19 TC 5 Z9 5 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 2008 VL 29 IS 12 BP 2706 EP 2713 DI 10.1002/elps.200700837 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 323XI UT WOS:000257481300028 PM 18512681 ER PT J AU Briese, T Renwick, N Venter, M Jarman, RG Ghosh, D Kondgen, S Shrestha, SK Hoegh, AM Casas, I Adjogoua, EV Akoua-Koffi, C Myint, KS Williams, DT Chidlow, G van den Berg, R Calvo, C Koch, O Palacios, G Kapoor, V Villari, J Dominguez, SR Holmes, KV Harnett, G Smith, D Mackenzie, JS Ellerbrok, H Schweiger, B Schonning, K Chadha, MS Leendertz, FH Mishra, AC Gibbons, RV Holmes, EC Lipkin, WI AF Briese, Thomas Renwick, Neil Venter, Marietjie Jarman, Richard G. Ghosh, Dhrubaa Koendgen, Sophie Shrestha, Sanjaya K. Hoegh, A. Mette Casas, Inmaculada Adjogoua, Edgard Valerie Akoua-Koffi, Chantal Myint, Khin Saw Williams, David T. Chidlow, Glenys van den Berg, Ria Calvo, Cristina Koch, Orienka Palacios, Gustavo Kapoor, Vishal Villari, Joseph Dominguez, Samuel R. Holmes, Kathryn V. Harnett, Gerry Smith, David Mackenzie, John S. Ellerbrok, Heinz Schweiger, Brunhilde Schonning, Kristian Chadha, Mandeep S. Leendertz, Fabian H. Mishra, A. C. Gibbons, Robert V. Holmes, Edward C. Lipkin, W. Ian TI Global distribution of novel rhinovirus genotype SO EMERGING INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY-TRACT; CHILDREN; INFECTIONS; PATHOGENS; ILLNESS AB Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years. C1 [Briese, Thomas] Columbia Univ, Ctr Infect & Immun, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Venter, Marietjie; van den Berg, Ria; Koch, Orienka] Univ Pretoria, NHLS Tswhane Acad Div, ZA-0002 Pretoria, South Africa. [Jarman, Richard G.; Gibbons, Robert V.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. [Ghosh, Dhrubaa; Chadha, Mandeep S.; Mishra, A. C.] Natl Inst Virol, Pune, Maharashtra, India. [Koendgen, Sophie; Ellerbrok, Heinz; Schweiger, Brunhilde; Leendertz, Fabian H.] Robert Koch Inst, D-1000 Berlin, Germany. [Shrestha, Sanjaya K.] Walter Reed AFRIMS Res Unit Nepal, Kathmandu, Nepal. [Hoegh, A. Mette; Schonning, Kristian] Hvidovre Univ Hosp, DK-2650 Hvidovre, Denmark. [Casas, Inmaculada] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid, Spain. [Adjogoua, Edgard Valerie; Akoua-Koffi, Chantal] Inst Pasteur Cote Ivoire, Abidjan, Cote Ivoire. [Williams, David T.; Mackenzie, John S.] Curtin Univ Technol, Perth, WA, Australia. [Chidlow, Glenys; Harnett, Gerry; Smith, David] PathWest Lab, Nedlands, WA, Australia. [Calvo, Cristina] Severo Ochoa Hosp, Madrid, Spain. [Dominguez, Samuel R.; Holmes, Kathryn V.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Holmes, Edward C.] Penn State Univ, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Bethesda, MD 20892 USA. RP Briese, T (reprint author), Columbia Univ, Ctr Infect & Immun, Mailman Sch Publ Hlth, 722 W 168th St,18th Floor, New York, NY 10032 USA. EM thomas.briese@columbia.edu RI Venter, Marietjie/H-3032-2011; Williams, David/H-6750-2013; Valle, Ruben/A-7512-2013; Palacios, Gustavo/I-7773-2015; Casas, Inmaculada/H-9442-2015; Venter, Marietjie/P-9604-2016; OI Palacios, Gustavo/0000-0001-5062-1938; Casas, Inmaculada/0000-0003-1840-1198; Venter, Marietjie/0000-0003-2696-824X; Holmes, Edward/0000-0001-9596-3552 FU NHLBI NIH HHS [R01 HL083850, HL083850]; NIAID NIH HHS [AI051292, AI059576, AI062705, AI57158, P01 AI059576, R01 AI051292, U54 AI057158, UC1 AI062705] NR 16 TC 71 Z9 72 U1 0 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUN PY 2008 VL 14 IS 6 BP 944 EP 947 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 309MR UT WOS:000256465100014 PM 18507910 ER PT J AU Nielsen, L Knutson, B Carstensen, LL AF Nielsen, Lisbeth Knutson, Brian Carstensen, Laura L. TI Affect dynamics, affective forecasting, and aging SO EMOTION LA English DT Article DE aging; emotion experience; affective forecasting; reward processing; decision making ID AGE-DIFFERENCES; OLDER-ADULTS; OUTCOMES; EMOTION; MEMORY; ANTICIPATION; SALIENCE; CHOICE; TIME; LIFE AB Affective forecasting, experienced affect, and recalled affect were compared in younger and older adults during a task in which participants worked to win and avoid losing small monetary sums. Dynamic changes in affect were measured along valence and arousal dimensions, with probes during both anticipatory and consummatory task phases. Older and younger adults displayed distinct patterns of affect dynamics. Younger adults reported increased negative arousal during loss anticipation and positive arousal during gain anticipation. In contrast, older adults reported increased positive arousal during gain anticipation but showed no increase in negative arousal on trials involving loss anticipation. Additionally, younger adults reported large increases in valence after avoiding an anticipated loss, but older adults did not. Younger, but not older, adults exhibited forecasting errors on the arousal dimension, underestimating increases in arousal during anticipation of gains and losses and overestimating increases in arousal in response to gain outcomes. Overall, the findings are consistent with a growing literature suggesting that older people experience less negative emotion than their younger counterparts and further suggest that they may better predict dynamic changes in affect. C1 [Nielsen, Lisbeth] NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. [Nielsen, Lisbeth; Knutson, Brian; Carstensen, Laura L.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Nielsen, L (reprint author), NIA, Behav & Social Res Program, NIH, 7201 Wisconsin Ave,Suite 533, Bethesda, MD 20892 USA. EM nielsenli@nia.nih.gov OI Knutson, Brian/0000-0002-7669-426X FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [F32 AG22727, F32 AG022727, F32 AG022727-02, P30 AG024957, P30-AG017253, P30 AG017253, R01-AG08816, R01 AG008816, P30-AG024957] NR 27 TC 49 Z9 51 U1 4 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2008 VL 8 IS 3 BP 318 EP 330 DI 10.1037/1528-3542.8.3.318 PG 13 WC Psychology, Experimental SC Psychology GA 310EY UT WOS:000256512900002 PM 18540748 ER PT J AU Grillon, C AF Grillon, Christian TI Greater sustained anxiety but not phasic fear in women compared to men SO EMOTION LA English DT Article DE fear; anxiety; sex difference; startle; unpredictability ID POSTTRAUMATIC-STRESS-DISORDER; POTENTIATED STARTLE; BASE-LINE; HUMANS; SYMPTOMS; EVENTS; GENDER AB Startle reflex studies in rodents indicate that female are more reactive than rats in experimental models of sustained anxiety but not in models of phasic fear (Toufexis, 2007). This study examined evidence for a similar effect in humans. Participants were exposed to three conditions, (1) predictable aversive shocks signaled by a cue, (2) unpredictable shocks, and (3) no shocks. Acoustic startle stimuli were delivered regularly across conditions. Phasic startle potential to the threat cue in the predictable condition was not affected by sex. In contrast, and consistent with basic research, the sustained increase in startle in the predictable and unpredictable conditions was greater in women compared to men. Animal studies suggest that such an effect may be mediated by the effects of sexual dimorphism in limbic structures, including the bed nucleus of the stria terminalis. However, psychosocial factors may also contribute to this effect. C1 [Grillon, Christian] NIMH, Mood & Anxiety Disorder Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH MAP 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM christian.grillon@nih.gov FU Intramural NIH HHS [Z01 MH002798-06] NR 27 TC 19 Z9 20 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2008 VL 8 IS 3 BP 410 EP 413 DI 10.1037/1528-3542.8.3.410 PG 4 WC Psychology, Experimental SC Psychology GA 310EY UT WOS:000256512900010 PM 18540756 ER PT J AU Ait-Ali, D Turquier, V Tanguy, Y Thouennon, E Ghzili, H Mounien, L Derambure, C Jegou, S Salier, JP Vaudry, H Eiden, LE Anouar, Y AF Ait-Ali, Djida Turquier, Valerie Tanguy, Yannick Thouennon, Erwan Ghzili, Hafida Mounien, Lourdes Derambure, Celine Jegou, Sylvie Salier, Jean-Philippe Vaudry, Hubert Eiden, Lee E. Anouar, Youssef TI Tumor necrosis factor (TNF)-alpha persistently activates nuclear Factor-kappa B signaling through the type 2 TNF receptor in chromaffin cells: Implications for long-term regulation of neuropeptide gene expression in inflammation SO ENDOCRINOLOGY LA English DT Article ID AIRWAY SMOOTH-MUSCLE; PROTEIN-KINASE-C; INTRACELLULAR CALCIUM; NITRIC-OXIDE; FACTOR-ALPHA; ADRENOCHROMAFFIN CELLS; TRANSCRIPTION FACTORS; MESSENGER-RNAS; T-LYMPHOCYTES; GALANIN GENE AB Chromaffin cells of the adrenal medulla elaborate and secrete catecholamines and neuropeptides for hormonal and paracrine signaling in stress and during inflammation. We have recently documented the action of the cytokine TNF-alpha on neuropeptide secretion and biosynthesis in isolated bovine chromaffin cells. Here, we demonstrate that the type 2 TNF-alpha receptor (TNF-R2) mediates TNF-alpha signaling in chromaffin cells via activation of nuclear factor (NF)-kappa B. Microarray and suppression subtractive hybridization have been used to identify TNF-alpha target genes in addition to those encoding the neuropeptides galanin, vasoactive intestinal polypeptide, and secretogranin II in chromaffin cells. TNF-alpha, acting through the TNF-R2, causes an early up-regulation of NF-kappa B, long-lasting induction of the NF-kappa B target gene inhibitor B (I kappa B), and persistent stimulation of other NF-kappa B-associated genes including mitogen-inducible gene-6 (MIG-6), which acts as an I kappa B signaling antagonist, and butyrate-induced transcript 1. Consistent with long-term activation of the NF-kappa B signaling pathway, delayed induction of neuropeptide gene transcription by TNF-alpha in chromaffin cells is blocked by an antagonist of NF-kappa B signaling. TNF-alpha-dependent signaling in neuroendocrine cells thus leads to a unique, persistent mode of NF-kappa B activation that features long-lasting transcription of both I kappa B and MIG-6, which may play a role in the long-lasting effects of TNF-alpha in regulating neuropeptide output from the adrenal, a potentially important feedback station for modulating longterm cytokine effects in inflammation. C1 [Ait-Ali, Djida; Turquier, Valerie; Tanguy, Yannick; Thouennon, Erwan; Ghzili, Hafida; Mounien, Lourdes; Jegou, Sylvie; Vaudry, Hubert; Anouar, Youssef] Univ Rouen, INSERM, European Inst Peptide Res IFRM23, Lab Cellular & Mol Neuroendocrinol,U413, F-76821 Mont St Aignan, France. [Ait-Ali, Djida; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. [Derambure, Celine; Salier, Jean-Philippe] Fac Med & Pharm, European Inst Peptide Res, INSERM, U519, F-76183 Rouen, France. RP Anouar, Y (reprint author), Univ Rouen, INSERM, European Inst Peptide Res IFRM23, Lab Cellular & Mol Neuroendocrinol,U413, F-76821 Mont St Aignan, France. EM youssef.anouar@univ-rouen.fr OI Eiden, Lee/0000-0001-7524-944X FU NIMH NIH HHS [Z01 MH002386] NR 59 TC 17 Z9 17 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2008 VL 149 IS 6 BP 2840 EP 2852 DI 10.1210/en.2007-1192 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303PP UT WOS:000256053100021 PM 18292192 ER PT J AU Sackett, DL Ozbun, L Zudaire, E Wessner, L Chirgwin, JM Cuttitta, F Martinez, A AF Sackett, Dan L. Ozbun, Laurent Zudaire, Enrique Wessner, Lisa Chirgwin, John M. Cuttitta, Frank Martinez, Alfredo TI Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function SO ENDOCRINOLOGY LA English DT Article ID TERMINAL 20 PEPTIDE; BETA-TUBULIN; TUMOR-CELLS; ADRENOMEDULLIN EXPRESSION; CARDIAC-HYPERTROPHY; ELECTRON-MICROSCOPY; HUMAN LUNG; PROTEIN; RAT; PACLITAXEL AB Adrenomedullin ( AM) and proadrenomedullin N-terminal 20 peptide ( PAMP) are secretory hormones, but it is not unusual to find them in intracellular compartments. Using yeast-2 hybrid technology, we found interactions between AM and several microtubule-associated proteins (MAPs), and between PAMP and tubulin. Expression of fluorescent-tagged AM and PAMP as well as immunofluorescence for the native peptides showed a complete decoration of the microtubules and colocalization with other MAPs. PAMP, but not AM, bound to tubulin in vitro and destabilized tubulin polymerization. Downregulation the gene coding for both AM and PAMP through small interfering RNA technology resulted in morphological changes, microtubule stabilization, increase in posttranslational modifications of tubulin such as acetylation and detyrosination, reduction in cell motility, and partial arrest at the G2 phase of the cell cycle, when compared with cells transfected with the same vector carrying a scrambled sequence. These results show that PAMP is a novel MAP, whereas AM maybe exerting more subtle effects in regulating cytoskeleton function. C1 [Sackett, Dan L.] NCI, Lab Integrat & Med Biophys, NICHHD, Bethesda, MD 20892 USA. [Ozbun, Laurent] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. [Zudaire, Enrique; Cuttitta, Frank] NCI, Angiogenesis Core Facil, Gaithersburg, MD 20877 USA. [Wessner, Lisa; Chirgwin, John M.] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA. [Martinez, Alfredo] CSIC, Inst Cajal, Dept Mol Cellular & Dev Neurobiol, E-28002 Madrid, Spain. RP Martinez, A (reprint author), CSIC, Inst Cajal, Dept Mol Cellular & Dev Neurobiol, E-28002 Madrid, Spain. EM amartinez@cajal.csic.es RI Martinez, Alfredo/A-3077-2013; Cuttitta, Frank/B-4758-2016 OI Martinez, Alfredo/0000-0003-4882-4044; NR 67 TC 12 Z9 14 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 JUN PY 2008 VL 149 IS 6 BP 2888 EP 2898 DI 10.1210/en.2007-1763 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303PP UT WOS:000256053100025 PM 18325988 ER PT J AU Sinkevicius, KW Burdette, JE Woloszyn, K Hewitt, SC Hamilton, K Sugg, SL Temple, KA Wondisford, FE Korach, KS Woodruff, TK Greene, GL AF Sinkevicius, Kerstin W. Burdette, Joanna E. Woloszyn, Karolina Hewitt, Sylvia C. Hamilton, Katherine Sugg, Sonia L. Temple, Karla A. Wondisford, Fredric E. Korach, Kenneth S. Woodruff, Teresa K. Greene, Geoffrey L. TI An estrogen receptor-alpha knock-in mutation provides evidence of ligand-independent signaling and allows modulation of ligand-induced pathways in vivo SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE; ER-ALPHA; OVARIAN-TUMORS; NULL MICE; MOUSE; BETA; INDUCTION; ESTRADIOL; EXCISION; BINDING AB Estrogen-nonresponsive estrogen receptor-alpha (ER alpha) knock-in (ENERKI) mice were generated to distinguish between ligand-induced and ligand-independent ER-alpha actions in vivo. These mice have a mutation [glycine 525 to leucine (G525L)] in the ligand-binding domain of ER alpha, which significantly reduces ER alpha interaction with and response to endogenous estrogens, whereas not affecting growth factor activation of ligand-independent pathways. ENERKI mice had hypoplastic uterine tissues and rudimentary mammary gland ductal trees. Females were infertile due to anovulation, and their ovaries contained hemorrhagic cystic follicles because of chronically elevated levels of LH. The ENERKI phenotype confirmed that ligand-induced activation of ER alpha is crucial in the female reproductive tract and mammary gland development. Growth factor treatments induced uterine epithelial proliferation in ovariectomized ENERKI females, directly demonstrating that ER alpha ligand-independent pathways were active. In addition, the synthetic ER alpha selective agonist propyl pyrazole triol (PPT) and ERagonist diethylstilbestrol (DES) were still able to activate ligand-induced G525L ER alpha pathways in vitro. PPT treatments initiated at puberty stimulated ENERKI uterine development, whereas neonatal treatments were needed to restore mammary gland ductal elongation, indicating that neonatal ligand-induced ER alpha activation may prime mammary ducts to become more responsive to estrogens in adult tissues. This is a useful model for in vivo evaluation of ligand-induced ER alpha pathways and temporal patterns of response. DES did not stimulate an ENERKI uterotrophic response. Because ER beta may modulate ER alpha activation and have an antiproliferative function in the uterus, we hypothesize that ENERKI animals were particularly sensitive to DES-induced inhibition of ER alpha due to up-regulated uterine ER beta levels. C1 [Sinkevicius, Kerstin W.; Woloszyn, Karolina; Greene, Geoffrey L.] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Temple, Karla A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Temple, Karla A.] Univ Chicago, Comm Mol Metab & Nutr, Chicago, IL 60637 USA. [Burdette, Joanna E.] Univ Illinois, Chicago, IL 60612 USA. [Hewitt, Sylvia C.; Hamilton, Katherine; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Sugg, Sonia L.] Univ Iowa, Dept Surg, Div Surg Oncol & Endocrine Surg, Iowa City, IA 52242 USA. [Wondisford, Fredric E.] Johns Hopkins Sch Med, Div Metab, Dept Pediat, Baltimore, MD 21287 USA. [Wondisford, Fredric E.] Johns Hopkins Sch Med, Div Metab, Dept Med, Baltimore, MD 21287 USA. [Wondisford, Fredric E.] Johns Hopkins Sch Med, Div Metab, Dept Physiol, Baltimore, MD 21287 USA. [Woodruff, Teresa K.] Northwestern Univ, Inst Womens Hlth Res, Feinberg Sch Med, Chicago, IL 60611 USA. RP Greene, GL (reprint author), Univ Chicago, Ben May Dept Canc Res, 929 E 57th St,GCIS W330, Chicago, IL 60637 USA. EM ggreene@uchicago.edu OI Korach, Kenneth/0000-0002-7765-418X FU NCI NIH HHS [CA89089]; NICHD NIH HHS [HD044464, R01 HD044464, K12 HD055892, K12 HD055892-03] NR 32 TC 42 Z9 42 U1 0 U2 1 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 JUN PY 2008 VL 149 IS 6 BP 2970 EP 2979 DI 10.1210/en.2007-1526 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303PP UT WOS:000256053100034 PM 18339713 ER PT J AU Kovacs, J Masur, H AF Kovacs, Joseph Masur, Henry TI HIV related opportunistic infections: still relevant after 25 years of AIDS progress SO ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA LA English DT Editorial Material ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED IMMUNODEFICIENCY C1 [Kovacs, Joseph; Masur, Henry] NIH, Dept Crit Care Med, NIH Clin Ctr, Bethesda, MD 20892 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, NIH Clin Ctr, Bethesda, MD 20892 USA. EM hmasur@nih.gov NR 10 TC 3 Z9 3 U1 0 U2 1 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0213-005X J9 ENFERM INFEC MICR CL JI Enferm. Infec. Microbiol. Clin. PD JUN-JUL PY 2008 VL 26 IS 6 BP 323 EP 324 PG 2 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 320GA UT WOS:000257220500001 PM 18588812 ER PT J AU Cooper, GS Gilbert, KM Greidinger, EL James, JA Pfau, JC Reinlib, L Richardson, BC Roses, NR AF Cooper, Glinda S. Gilbert, Kathleen M. Greidinger, Eric L. James, Judith A. Pfau, Jean C. Reinlib, Leslie Richardson, Bruce C. Roses, Noel R. TI Recent advances and opportunities in research on lupus: Environmental influences and mechanisms of disease SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE adjuvant effect; apoptosis; autoimmune diseases; bystander effect; demethylation; epigenetics; Epstein-Barr virus; silica; systemic lupus erythematosus; trichloroethylene ID EPSTEIN-BARR-VIRUS; ZEALAND MIXED MICE; T-CELL-ACTIVATION; KINASE-C-DELTA; SYSTEMIC AUTOIMMUNE-DISEASE; TUMOR-NECROSIS-FACTOR; RESISTANT B10.A MICE; APOPTOTIC CELLS; MURINE MODEL; ALVEOLAR MACROPHAGES AB OBJECTIVES: In this review we summarize research on mechanisms through which environmental agents may affect the pathogenesis of lupus, discuss three exposures that have been the focus of research in this area, and propose recommendations for new research initiatives. DATA SOURCES AND SYNTHESIS: We examined studies pertaining to key mechanistic events and specific exposures. Apoptosis leading to increased production or decreased clearance of immunogenic intracellular self-antigens and defective apoptosis of autoreactive immune cells both have been implicated in the loss of self-tolerance. The adjuvant or bystander effect is also needed to produce a sustained autoimmune response. Activation of toll-like receptors is one mechanism through which these effects may occur. Abnormal DNA methylation may also contribute to the pathogenesis of lupus. Each of the specific exposures we examined-Epstein-Barr virus, silica, and trichloroethylene-has been shown, in humans or in mice, to act upon one or more of these pathogenic steps. Specific recommendations for the continued advancement of our understanding of environmental influences on lupus and other autoimmune diseases include the development and use of mouse models with varying degrees of penetrance and manifestations of disease, identification of molecular or physiologic targets of specific exposures, development and use of improved exposure assessment methodologies, and multisite collaborations designed to examine understudied environmental exposures in humans. CONCLUSIONS: The advances made in the past decade concerning our understanding of mechanisms involved in the development of lupus and the influence of environmental agents on this process provide a strong foundation for further developments in this field. C1 [Cooper, Glinda S.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Gilbert, Kathleen M.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72205 USA. [Greidinger, Eric L.] Univ Miami, Miller Sch Med, Miami Dept Vet Affairs Med Ctr, Div Rheumatol, Miami, FL USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Arthrit & Immunol Program, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Pfau, Jean C.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Pfau, Jean C.] Univ Montana, Ctr Environm Hlth Sci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. [Reinlib, Leslie] NIH, Div Extramural Res & training, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Richardson, Bruce C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Richardson, Bruce C.] Ann Arbor Vet Affairs Hosp, Ann Arbor, MI USA. [Roses, Noel R.] Johns Hopkins Univ, Johns Hopkins Ctr Autoimmune Dis Res, Dept Pathol, Baltimore, MD USA. RP Cooper, GS (reprint author), US EPA, Natl Ctr Environm Assessment P 8601, 1200 Penn Ave NW, Washington, DC 20460 USA. EM cooper.glinda@epa.gov OI Greidinger, Eric/0000-0003-3473-3846 FU NIAMS NIH HHS [P30 AR053483] NR 107 TC 45 Z9 49 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 JUN PY 2008 VL 116 IS 6 BP 695 EP 702 DI 10.1289/ehp.11092 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 306NC UT WOS:000256254100019 PM 18560522 ER PT J AU Slotkin, TA MacKillop, EA Melnick, RL Thayer, KA Seidler, FJ AF Slotkin, Theodore A. MacKillop, Emiko A. Melnick, Ronald L. Thayer, Kristina A. Seidler, Frederic J. TI Developmental neurotoxicity of perfluorinated chemicals modeled in vitro SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE developmental neurotoxicity; PC12 cells; perfluorinated chemicals; perfluoroalkyl acids; perfluorobutane sulfonate; perfluorooctane sulfonamide; perfluorooctane sulfonate; perfluorooctanoate; perfluorooctanoic acid ID PC12 CELLS; PERFLUOROOCTANE SULFONATE; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; PHEOCHROMOCYTOMA CELLS; IRREVERSIBLE INHIBITOR; OCCUPATIONAL-EXPOSURE; PERFLUOROALKYL ACIDS; LIVER-MICROSOMES; OXIDATIVE STRESS AB BACKGROUND: The widespread detection of perfluoroalkyl acids and their derivatives in wildlife and humans, and their entry into the immature brain, raise increasing concern about whether these agents might be developmental neurotoxicants. OBJECTIVES: We evaluated perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), and perfluorobutane sulfonate (PFBS) in undifferentiated and differentiating PC12 cells, a neuronotypic line used to characterize neurotoxicity. METHODS: We assessed inhibition of DNA synthesis, deficits in cell numbers and growth, oxidative stress, reduced cell viability, and shifts in differentiation toward or away from the dopamine (DA) and acetylcholine (ACh) neurotransmitter phenotypes. RESULTS: In general, the rank order of adverse effects was PFOSA > PFOS > PFBS approximate to PFOA. However, superimposed on this scheme, the various agents differed in their underlying mechanisms and specific outcomes. Notably, PFOS promoted differentiation into the ACh phenotype at the expense of the DA phenotype, PFBS suppressed differentiation of both phenotypes, PFOSA enhanced differentiation of both, and PFOA had little or no effect on phenotypic specification. CONCLUSIONS: These findings indicate that all perfluorinated chemicals are not the same in their impact on neurodevelopment and that it is unlikely that there is one simple, shared mechanism by which they all produce their effects. Our results reinforce the potential for in vitro models to aid in the rapid and cost-effective screening for comparative effects among different chemicals in the same class and in relation to known developmental neurotoxicants. C1 [Slotkin, Theodore A.; MacKillop, Emiko A.; Seidler, Frederic J.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Melnick, Ronald L.; Thayer, Kristina A.] NIH, Natl Toxicol Program, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813 DUMC, Durham, NC 27710 USA. EM t.slotkin@duke.edu FU PHS HHS [HHSN27320062006C] NR 65 TC 68 Z9 84 U1 6 U2 45 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 JUN PY 2008 VL 116 IS 6 BP 716 EP 722 DI 10.1289/ehp.11253 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 306NC UT WOS:000256254100022 PM 18560525 ER PT J AU Yanagiba, Y Ito, Y Yamanoshita, O Zhang, SY Watanabe, G Taya, K Li, CM Inotsume, Y Kamijima, M Gonzalez, FJ Nakajima, T AF Yanagiba, Yukie Ito, Yuki Yamanoshita, Osamu Zhang, Shu-Yun Watanabe, Gen Taya, Kazuyoshi Li, Chun Mei Inotsume, Yuko Kamijima, Michihiro Gonzalez, Frank J. Nakajima, Tamie TI Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor (AhR) target gene UDP-glucuronosyltransferase SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aryl hydrocarbon receptor; cytochrome P450 1A; styrene trimer; thyroid hormone; UDP-glucuronosyltransferase ID TEA EXTRACT CATECHINS; POLYSTYRENE CONTAINERS; ENHANCER MODULE; MICE LACKING; RATS; OLIGOMERS; COMPLEX; THYROXINE; INDUCTION; DIOXIN AB BACKGROUND: Styrene trimers (STs) are polystyrene-container-eluted materials that are sometimes detected in packaged foods. Although the possible endocrine-disrupting effects Of STs, such as estrogenic activities, have been reported, their potential thyroid toxicity, such as that caused by the related endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has not been studied in detail. OBJECTIVE: Using wild-type and aryl hydrocarbon receptor (Ahr)-null mice, we investigated whether 2,4,6-triphenyl-1-hexene (ST-1), an isomer of STs, influences thyroxin (T-4) levels in the same manner as TCDD, which induces UDP-glucuronosyltransferase (UGT) via the AhR, resulting in a decrease in T4 levels in the plasma of mice. METHODS: Both wild-type and Ahr-null mice (five mice per group) were treated for 4 days by gavage with ST-1 (0, 32, or 64 mu mol/kg). RESULTS: High-dose (64 mu mol/kg) ST-1 decreased the expression of AhR, cytochrome P450 (CYP) 1A1/2, UGT1A1/A6, and CYP2B10 mRNAs and the enzyme activity for CYP1A and UGT1A only in the wild-type mice. This dose decreased AhR DNA binding, but paradoxically increased AhR translocation to the nucleus. In contrast, a high dose of ST-1 increased T-4 levels in the plasma in wild-type mice but did not influence T-4 levels in AhR-null mice. CONCLUSIONS: Although ST-1 treatment might cause an increase in AhR levels in the nucleus by inhibiting AhR export, this chemical down-regulated AhR mRNA, thus leading to down-regulation of AhR target genes and an increase in plasma T-4 levels. C1 [Yanagiba, Yukie; Ito, Yuki; Zhang, Shu-Yun; Inotsume, Yuko; Kamijima, Michihiro; Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Showa Ku, Dept Environm & Occupat Hlth, Nagoya, Aichi 4668550, Japan. [Yamanoshita, Osamu] Chubu Univ, Dept Biomed Sci, Coll Life & Hlth Sci, Kasugai, Aichi 487, Japan. [Watanabe, Gen; Taya, Kazuyoshi] Gifu Univ, Dept Vet Basic Sci, United Grad Sch Vet Sci, Gifu, Japan. [Watanabe, Gen; Taya, Kazuyoshi] Tokyo Univ Agr & Technol, Dept Vet Med, Fac Agr, Tokyo, Japan. [Li, Chun Mei] Natl Inst Environm Studies, Ibaraki, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Nakajima, T (reprint author), Nagoya Univ, Grad Sch Med, Showa Ku, Dept Environm & Occupat Hlth, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM tnasu23@med.nagoya-u.ac.jp RI Ito, Yuki/C-3698-2008; Watanabe, Gen/G-1134-2013 OI Watanabe, Gen/0000-0001-7611-4678 NR 38 TC 14 Z9 14 U1 1 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2008 VL 116 IS 6 BP 740 EP 745 DI 10.1289/ehp.10724 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 306NC UT WOS:000256254100026 PM 18560529 ER PT J AU Gohlke, JM Hrynkow, SH Portier, CJ AF Gohlke, Julia M. Hrynkow, Sharon H. Portier, Christopher J. TI Health, economy, and environment: Sustainable energy choices for a nation SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID EMISSIONS C1 [Gohlke, Julia M.; Hrynkow, Sharon H.; Portier, Christopher J.] NIH, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Gohlke, JM (reprint author), NIH, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM portier@niehs.nih.gov RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Gohlke, Julia/0000-0002-6984-2893 NR 12 TC 2 Z9 2 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2008 VL 116 IS 6 BP A236 EP A237 DI 10.1289/ehp.11602 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 306NC UT WOS:000256254100002 PM 18560493 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Genomes of model organisms: know thy tools SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SP-NOV.; HALOBACTERIUM-SALINARUM; MYCOBACTERIUM-ABSCESSUS; CHLAMYDOMONAS-REINHARDTII; ACINETOBACTER-BAUMANNII; BACILLUS-SPHAERICUS; COMB.-NOV; SEQUENCE; PHOTOSYNTHESIS; PROTEOBACTERIA C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 64 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD JUN PY 2008 VL 10 IS 6 BP 1383 EP 1391 DI 10.1111/j.1462-2920.2008.01656.x PG 9 WC Microbiology SC Microbiology GA 298QJ UT WOS:000255701900001 PM 18474084 ER PT J AU Longnecker, MP Smith, CS Kissling, GE Hoppin, JA Butenhoff, JL Decker, E Ehresman, DJ Ellefson, ME Flaherty, J Gardner, MS Langlois, E LeBlanc, A Lindstrom, AB Reagen, WK Strynar, MJ Studabaker, WB AF Longnecker, Matthew P. Smith, Cynthia S. Kissling, Grace E. Hoppin, Jane A. Butenhoff, John L. Decker, Emily Ehresman, David J. Ellefson, Mark E. Flaherty, John Gardner, Michael S. Langlois, Eric LeBlanc, Alain Lindstrom, Andrew B. Reagen, William K. Strynar, Mark J. Studabaker, William B. TI An interlaboratory study of perfluorinated alkyl compound levels in human plasma SO ENVIRONMENTAL RESEARCH LA English DT Article DE perfluorinated alkyl compounds; interlaboratory study; persistent organic pollutants; interdisciplinary studies; research design; epidemiologic methods ID PERFLUOROOCTANESULFONATE PFOS; BLOOD-DONORS; FLUOROCHEMICALS; EXPOSURE; SERUM; POPULATION; SUBSTANCES; CHEMICALS; HEALTH AB We conducted an interlaboratory study which differed from the typical study of this type because of its emphasis on comparing intralaboratory variability in results. We sent specimens to six laboratories experienced in the analysis of perfluorinated alkyl compounds in blood matrices and that use stringent procedures to control and assure accuracy and precision. Each received an identical set of 60 plasma specimens that were analyzed in six completely independent batches. Split specimens were included so that within- and between-batch coefficients of variation could be calculated. All laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) measured in the specimens in general showed a high level of agreement, although in some cases the agreement was only moderate. The average within- and between-batch coefficient of variation for PFOS was 9.1% and 9.3%; for PFOA was 14.5% and 14.5%; and for PFHxS was 14.5% and 17.0%. The recent availability of labeled internal standards, among other advances, has facilitated improvement in the accuracy and precision of the assays. Considering the degree of between-subject variation in levels among people in background-exposed populations, the results indicate that biomarker-based epidemiologic studies of associations with health could have reasonable precision. (C) 2008 Elsevier Inc. All rights reserved. C1 [Longnecker, Matthew P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Smith, Cynthia S.] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Butenhoff, John L.; Ehresman, David J.; Ellefson, Mark E.; Reagen, William K.] 3M Co, St Paul, MN 55144 USA. [Decker, Emily; Flaherty, John] Exygen Res, State Coll, PA USA. [Gardner, Michael S.; Studabaker, William B.] Res Triangle Inst Int, Exposure Anal Res Program, Res Triangle Pk, NC USA. [Langlois, Eric; LeBlanc, Alain] Inst Natl Sante Publ Quebec, Toxicol Lab, Quebec City, PQ, Canada. [Lindstrom, Andrew B.; Strynar, Mark J.] US EPA, Human Exposure & Atmospher Sci Div, Natl Exposure Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnecl@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 FU Intramural NIH HHS [Z01 ES044008-07] NR 27 TC 28 Z9 29 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JUN PY 2008 VL 107 IS 2 BP 152 EP 159 DI 10.1016/j.envres.2008.01.005 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 307PQ UT WOS:000256331200003 PM 18295197 ER PT J AU Kang, D Park, SK Beane-Freeman, L Lynch, CF Knott, CE Sandler, DP Hoppin, JA Dosemeci, M Coble, J Lubin, J Blair, A Alavanja, M AF Kang, Daehee Park, Sue Kyung Beane-Freeman, Laura Lynch, Charles F. Knott, Charles E. Sandler, Dale P. Hoppin, Jane A. Dosemeci, Mustafa Coble, Joseph Lubin, Jay Blair, Aaron Alavanja, Michael TI Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study SO ENVIRONMENTAL RESEARCH LA English DT Article DE agriculture; trifluralin; pesticides; cancer; occupational exposure ID SOFT-TISSUE SARCOMA; HERBICIDE TRIFLURALIN; COLON CANCER; GENOTOXICITY; LYMPHOMA; RISK; TRIALLATE; PHENOXY; FARMERS; ACID AB Trifluralin, 2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline, is a 2,6-dinitro herbicide widely used to control annual grasses and broadleaf weeds in agricultural settings. The association between trifluralin use and common cancer incidence was evaluated among 50,127 private and commercial pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina. Poisson regression was used to examine internal dose-response relationships, while controlling for important lifestyle factors and other agricultural exposures. Two metrics of exposure (lifetime days and intensity-weighted lifetime days) were used in exposure-response analyses with non-exposed applicators, as well as applicators in the lowest tertile of exposure, as reference groups. Incident cancers were identified through state tumor registries from enrollment in 1993 through 2002. Trifluralin exposure was not associated with cancer incidence overall among 51% of private and commercial applicators (n = 25,712) who had used trifluralin. However, there was an excess of colon cancer in the exposure category of higher half of highest tertile (rate ratios (RR) of 1.76 (95% CI = 1.05-2.95) using the non-exposed as a referent and 1.93 (95% CI = 1.08-3.45) using those with the lowest tertile of exposure as the referent). There was also a non-significantly elevated risk for kidney cancer and bladder cancer in the highest exposure group, although only the kidney cancer finding was consistent across exposure metrics. Although there was a possible link between trifluralin exposure and colon cancer, small numbers and inconsistencies in dose-response and subgroup analyses indicate that this may be a chance finding. Published by Elsevier Inc. C1 [Kang, Daehee; Beane-Freeman, Laura; Dosemeci, Mustafa; Coble, Joseph; Lubin, Jay; Blair, Aaron; Alavanja, Michael] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. [Kang, Daehee; Park, Sue Kyung] Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Sandler, Dale P.; Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, DHHS, Durham, NC USA. RP Alavanja, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 8000, Rockville, MD 20852 USA. EM alavanjm@mail.nih.gov RI Kang, Dae Hee/E-8631-2012; Park, Sue Kyung/J-2757-2012; Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 28 TC 26 Z9 28 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JUN PY 2008 VL 107 IS 2 BP 271 EP 276 DI 10.1016/j.envres.2008.01.010 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 307PQ UT WOS:000256331200016 PM 18342850 ER PT J AU Gupta, SK Keck, J Ram, PK Crump, JA Miller, MA Mintz, ED AF Gupta, S. K. Keck, J. Ram, P. K. Crump, J. A. Miller, M. A. Mintz, E. D. TI Part III. Analysis of data gaps pertaining to enterotoxigenic Escherichia coli infections in low and medium human development index countries, 1984-2005 SO EPIDEMIOLOGY AND INFECTION LA English DT Review ID COLONIZATION FACTOR ANTIGENS; DIARRHEAL DISEASE; YOUNG-CHILDREN; CHILDHOOD DIARRHEA; PERSISTENT DIARRHEA; ETIOLOGIC AGENTS; CAMPYLOBACTER-JEJUNI; BACTERIAL PATHOGENS; TRAVELERS DIARRHEA; CLINICAL-FEATURES AB Enterotoxigenic Escherichia coli (ETEC) is a common cause of profuse watery diarrhoea in the developing world, often leading to severe dehydration or death. We found only 15 population-based Studies in low and medium human development index (HDI) Countries from 1984 to 2005 that evaluate disease incidence. Reported incidence ranged from 39 to 4460 infections/1000 persons per year. The peak incidence of ETEC appeared to Occur between ages 6 and 18 months. A median of 14% (range 2-36%.) of diarrhoeal specimens were positive for ETEC in 19 facility-and population-based studies conducted In all age groups and 13% (range 3-39 %) in 51 studies conducted in children only. Heat-labile toxin (LT)-ETEC is thought to be less likely to cause disease than heat-stable toxin (ST)-ETEC or LT/ST-ETEC. Because population-based Studies involve enhanced clinical management of patients and facility-based studies include only the most severe illnesses, reliable data on complications and mortality from ETEC infections Was unavailable. To reduce gaps in the current understanding of ETEC incidence, complications and mortality, large population-based studies combined with facility-based Studies covering a majority of the corresponding population are needed, especially in low-HDI Countries. Moreover, a standard molecular definition of ETEC infection is needed to be able to compare results across Study sites. C1 [Gupta, S. K.; Crump, J. A.; Mintz, E. D.] Ctr Dis Control & Prevent, Enter Dis Epidemiol Branch, Natl Ctr Zoonot Vectorborne Enter Dis, Atlanta, GA USA. [Keck, J.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Ram, P. K.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Miller, M. A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Gupta, SK (reprint author), CDC Global AIDS Program Cent Amer & Panama, Apartado Postal 3013, Tegucigalpa, Honduras. EM scg7@cdc.gov FU U.S. National Institutes of Health Fogarty International Center; Bill and Melinda Gates Foundation [32143] FX This work was supported in part by the U.S. National Institutes of Health Fogarty International Center and by grant number 32143 from the Bill and Melinda Gates Foundation 'Assessment of diarrhoea disease burden and public health programs to control diarrhoea in Asian Subcontinent and Africa NR 107 TC 39 Z9 39 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JUN PY 2008 VL 136 IS 6 BP 721 EP 738 DI 10.1017/S095026880700934X PG 18 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 348GH UT WOS:000259198500001 PM 17686197 ER PT J AU Chowell, G Miller, MA Viboud, C AF Chowell, G. Miller, M. A. Viboud, C. TI Seasonal influenza in the United States, France, and Australia: transmission and prospects for control SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID PANDEMIC INFLUENZA; EPIDEMIC INFLUENZA; HONG-KONG; MORTALITY; VACCINATION; IMPACT; CHILDREN; POPULATION; DYNAMICS; SPREAD AB Recurrent epidemics of influenza are observed seasonally around the world with considerable health and economic consequences. A key quantity for the control of infectious diseases is the reproduction number, which measures the transmissibility of a pathogen and determines the magnitude of public health interventions necessary to control epidemics. Here we applied a simple epidemic model to weekly indicators Of influenza mortality to estimate the reproduction numbers of seasonal influenza epidemics spanning three decades in the United States, France, and Australia.. We found similar distributions of reproduction number estimates in the three countries, with mean Value 1 center dot 3 and important year-to-year variability (range 0 center dot 9-2 center dot 1). Estimates derived from two different mortality indicators (pneumonia and influenza excess deaths and influenza-specific deaths) were in close agreement for the United States (correlation=0 center dot 61, P<0 center dot 001) and France (correlation =07 center dot 9, P<0 center dot 001), but not Australia. Interestingly, high prevalence of A/H3N2 influenza viruses was associated with high transmission seasons (P=0 center dot 006), while B Viruses were more prevalent in low transmission seasons (P = 0 center dot 004). The Current vaccination strategy targeted at people at highest risk of severe disease Outcome IS suboptimal because Current vaccines are poorly immunogenic in these Population groups. Our results Suggest that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (>60 in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning Population immunity. C1 [Chowell, G.] Los Alamos Natl Lab, Theoret Div MS B284, Los Alamos, NM 87544 USA. [Miller, M. A.; Viboud, C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Chowell, G (reprint author), Los Alamos Natl Lab, Theoret Div MS B284, Los Alamos, NM 87544 USA. EM chowell@lanl.gov RI Chowell, Gerardo/A-4397-2008; Chowell, Gerardo/F-5038-2012 OI Chowell, Gerardo/0000-0003-2194-2251 FU Los Alamos National Laboratory; Fogarty International Center, National Institutes of Health FX This study was funded by the Los Alamos National Laboratory and the Fogarty International Center, National Institutes of Health. NR 73 TC 120 Z9 122 U1 2 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JUN PY 2008 VL 136 IS 6 BP 852 EP 864 DI 10.1017/S0950268807009144 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 348GH UT WOS:000259198500013 PM 17634159 ER PT J AU Resnik, DB AF Resnik, David B. TI SCIENTIFIC AUTONOMY AND PUBLIC OVERSIGHT SO EPISTEME-A JOURNAL OF INDIVIDUAL AND SOCIAL EPISTEMOLOGY LA English DT Article AB When scientific research collides with social values, science's right to self-governance becomes an issue of paramount concern. In this article, I develop an account of scientific autonomy within a framework of public oversight. I argue that scientific autonomy is justified because it promotes the progress of science, which benefits society, but that restrictions on autonomy can also be justified to prevent harm to people, society, or the environment, and to encourage beneficial research. I also distinguish between different ways of limiting scientific autonomy, and I argue that government involvement in scientific decision-making should usually occur through policies that control the process of science, rather than policies that control the content of science. C1 NIEHS, NIH, Bethesda, MD 20892 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Bethesda, MD 20892 USA. NR 45 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1742-3600 EI 1750-0117 J9 EPISTEME-J INDIV SOC JI Episteme PD JUN PY 2008 VL 5 IS 2 BP 220 EP 238 DI 10.3366/E1742360008000336 PG 19 WC Philosophy SC Philosophy GA V32UP UT WOS:000208976400005 ER PT J AU Palmas, W Ma, SG Jacobs, DR Arnett, D Jackson, S Olson, J Saad, MF Kronmal, R Kramer, H Barr, RG AF Palmas, Walter Ma, Shuangge Jacobs, David R., Jr. Arnett, Donna Jackson, Sharon Olson, Jean Saad, Mohammed F. Kronmal, Richard Kramer, Holly Barr, R. Graham TI ETHNICITY AND SEX MODIFY THE ASSOCIATION OF SERUM C-REACTIVE PROTEIN WITH MICROALBUMINURIA SO ETHNICITY & DISEASE LA English DT Article DE Albuminuria; C-Reactive Protein; Ethnicity; Sex ID URINARY ALBUMIN EXCRETION; NUTRITION EXAMINATION SURVEY; TYPE-1 DIABETIC-PATIENTS; 3RD NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; RENAL-INSUFFICIENCY; HYPERTENSIVE MEN; CREATININE RATIO; RISK-FACTORS; FOLLOW-UP AB Objectives: To study the association between serum C-reactive protein (CRP) and urinary albumin excretion in the Multi-Ethnic Study of Atherosclerosis and to assess whether the association is modified by ethnicity, sex, or systolic blood pressure. Methods: This was a cross-sectional study of 6675 participants who were free from macroalbuminuria and clinical cardiovascular disease (mean age 62.1 years, 53% female; 39% White, 27% African American, 22% Hispanic, and 12% Chinese). Urinary albumin excretion was measured by spot urine albumin-to-creatinine ratio (ACR). Effect modifications were tested after adjusting for age, diabetes, body mass index, smoking. use of angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, other antihypertensive drugs, estrogens, statins, and high-density lipoprotein cholesterol and triglyceride levels. Results: The association between CRP and ACR was modified by ethnicity (P=.01) and sex (P<.001), but not by systolic blood pressure. After multivariate adjustment, the association remained in Chinese, African American, and Hispanic men and African American women (P<.02 for African American men, and P<.04 for the other subgroups). Conclusions: The association between CRP and ACR was modified by ethnicity and sex; it was stronger in non-White men and African American women. These interactions have not been reported before, and future studies should consider them. (Ethn Dis. 2008;18:324-329) C1 [Palmas, Walter; Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Med, New York, NY USA. [Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Ma, Shuangge; Kronmal, Richard] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Jacobs, David R., Jr.] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [Arnett, Donna] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Jackson, Sharon] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Olson, Jean] NHLBI, Bethesda, MD 20892 USA. [Saad, Mohammed F.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Kramer, Holly] Loyola Univ, Dept Prevent Med, Maywood, IL 60153 USA. [Kramer, Holly] Loyola Univ, Dept Med, Maywood, IL 60153 USA. RP Barr, RG (reprint author), Div Gen Med, 630 W 168th St,PH 9,East 105, New York, NY 10032 USA. EM rgb9@columbia.edu OI Kramer, Holly/0000-0002-6374-837X FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95161, N01-HC-95165, N01-HC-95166] FX We thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA inveitigators and institutions can be found at http://www.mesanhibi.org. This study was supported by contracts N01-HC-95159 through N01-HC-95161, N01-HC-95165, and N01-HC-95166 from the National Heart, Lung, and Blood Institute. NR 36 TC 4 Z9 4 U1 1 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2008 VL 18 IS 3 BP 324 EP 329 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 489MC UT WOS:000269423200010 PM 18785447 ER PT J AU Winters, K Wyatt, SB Akylbekova, E Walker, E Taylor, H AF Winters, K. Wyatt, S. B. Akylbekova, E. Walker, E. Taylor, H. TI HEALTH INSURANCE STATUS AND REPORTED ACCESS TO NEEDED HEALTH CARE: BASELINE FINDINGS FROM THE JACKSON HEART STUDY (JHS) SO ETHNICITY & DISEASE LA English DT Meeting Abstract C1 [Winters, K.; Wyatt, S. B.; Taylor, H.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Walker, E.] NHLBI, Jackson Heart Study, Jackson, MS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2008 VL 18 IS 3 MA 013 BP S12 EP S12 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 489MC UT WOS:000269423200033 ER PT J AU Harland, M Goldstein, AM Kukalizch, K Taylor, C Hogg, D Puig, S Badenas, C Gruis, N ter Huurne, J Bergman, W Hayward, NK Stark, M Tsao, H Tucker, MA Landi, MT Scarra, GB Ghiorzo, P Kanetsky, PA Elder, D Mann, GJ Holland, EA Bishop, DT Bishop, JN AF Harland, Mark Goldstein, Alisa M. Kukalizch, Kairen Taylor, Claire Hogg, David Puig, Susana Badenas, Celia Gruis, Nelleke ter Huurne, Jeanet Bergman, Wilma Hayward, Nicholas K. Stark, Mitchell Tsao, Hensin Tucker, Margaret A. Landi, Maria Teresa Scarra, Giovanna Bianchi Ghiorzo, Paola Kanetsky, Peter A. Elder, David Mann, Graham J. Holland, Elizabeth A. Bishop, D. Timothy Bishop, Julia Newton CA GenoMEL Melanoma Genetics Consorti TI A comparison of CDKN2A mutation detection within the Melanoma Genetics Consortium (GenoMEL) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE CDKN2A; melanoma; mutation detection; sequencing; polymorphism; audit; DHPLC; false negative ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GERMLINE MUTATIONS; FAMILIAL MELANOMA; DENATURING HPLC; DHPLC; CDK4; P16(INK4A); PREVALENCE; PEDIGREES; DELETIONS AB CDKN2A is the major melanoma susceptibility gene so far identified, but only 40% of three or more case families have identified mutations. A comparison of mutation detection rates was carried out by "blind" exchange of samples across GenoMEL, the Melanoma Genetics Consortium, to establish the false negative detection rates. Denaturing high performance liquid chromatography (DHPLC) screening results from 451 samples were compared to screening data from nine research groups in which the initial mutation screen had been done predominantly by sequencing. Three samples with mutations identified at the local centres were not detected by the DHPLC screen. No additional mutations were detected by DHPLC. Mutation detection across groups within GenoMEL is carried out to a consistently high standard. The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Harland, Mark; Kukalizch, Kairen; Bishop, D. Timothy; Bishop, Julia Newton] St James Univ Hosp, Canc Res UK Canc Ctr Leeds, Leeds Inst Mol Med, Div Epidemiol & Biostat, Leeds LS9 7TF, W Yorkshire, England. [Goldstein, Alisa M.; Tucker, Margaret A.; Landi, Maria Teresa] DHHS, NIH, Natl Canc Inst, Div Canc Epidemiol & Genet,Genet Epidemiol Branch, Bethesda, MD USA. [Taylor, Claire] St James Univ Hosp, Canc Res UK, Mutat Detect Facil, Leeds LS9 7TF, W Yorkshire, England. [Hogg, David] Univ Toronto, Inst Med Sci, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Puig, Susana; Badenas, Celia] IDIBAPS, Dept Dermatol, Barcelona, Spain. [Puig, Susana; Badenas, Celia] IDIBAPS, Genet Serv, Hosp Clin, Barcelona, Spain. [Gruis, Nelleke; ter Huurne, Jeanet; Bergman, Wilma] LUMC, Dept Dermatol, Leiden, Netherlands. [Gruis, Nelleke; ter Huurne, Jeanet; Bergman, Wilma] LUMC, Ctr Human & Clin Genet, Leiden, Netherlands. [Hayward, Nicholas K.; Stark, Mitchell] Queensland Inst Med Res, Human Genet Lab, Brisbane, Qld 4006, Australia. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Scarra, Giovanna Bianchi; Ghiorzo, Paola; Kanetsky, Peter A.] Univ Genoa, Dept Oncol Biol & Genet, I-16126 Genoa, Italy. [Kanetsky, Peter A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kanetsky, Peter A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Elder, David] Univ Penn, Pathol & Lab Med, Philadelphia, PA 19104 USA. [Mann, Graham J.; Holland, Elizabeth A.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. RP Bishop, JN (reprint author), St James Univ Hosp, Canc Res UK Canc Ctr Leeds, Leeds Inst Mol Med, Div Epidemiol & Biostat, Leeds LS9 7TF, W Yorkshire, England. EM j.a.newton-bishop@leeds.ac.uk RI Stark, Mitchell/E-3542-2010; Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; OI Stark, Mitchell/0000-0002-4510-2161; Mann, Graham/0000-0003-1301-405X; Puig, Susana/0000-0003-1337-9745; Bianchi Scarra, Giovanna/0000-0002-6127-1192; hayward, nicholas/0000-0003-4760-1033; Badenas, Celia/0000-0002-0621-0477; Gruis, Nelleke/0000-0002-5210-9150; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802 FU Cancer Research UK [A4994]; Intramural NIH HHS; NCI NIH HHS [R01 CA 83115, R01 CA 88363, R01 CA083115, R01 CA083115-01A2, R01 CA088363, R01 CA088363-01A1] NR 37 TC 17 Z9 18 U1 0 U2 0 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 JUN PY 2008 VL 44 IS 9 BP 1269 EP 1274 DI 10.1016/j.ejca.2008.03.005 PG 6 WC Oncology SC Oncology GA 326CZ UT WOS:000257636900023 PM 18394881 ER PT J AU Moradi, T Gridley, G Bjork, J Dosemeci, M Ji, BT Berkel, HJ Lemeshow, S AF Moradi, Tahereh Gridley, Gloria Bjork, Jan Dosemeci, Mustafa Ji, Bu-Tian Berkel, Hans J. Lemeshow, Stanley TI Occupational physical activity and risk for cancer of the colon and rectum in Sweden among men and women by anatomic subsite SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE cohort; colon and rectal neoplasm; occupational physical activity; subsite; Sweden ID DEFENSE FORCES HEALTH; COLORECTAL-CANCER; PROSPECTIVE COHORT; DIETARY PATTERNS; UNITED-STATES; LARGE BOWEL; ADENOMAS; GENDER; SEX; AGE AB Inverse association between physical activity and colon cancer is well established, at least in men. We investigated the association of occupational physical activity with subsite-specific colorectal cancer risk. On the basis of occupational titles from the Swedish nationwide censuses in 1960 and 1970, we defined a cohort of women and men with the same work-related physical demands in 1960 and 1970. Incidence of colon and rectum cancer during 1971-1989 was ascertained through linkages to the Cancer Register. Relative risks (RRs) were estimated through Poisson regression. The risk for colon cancer increased with decreasing occupational physical activity. RR among sedentary women and men was 1.2 and 1.3 (P for trend=0.08 and <0.001). For men, the risks for proximal and distal colon cancer increased by 20 and 40% (P for trend=0.005 and <0.001). Inactivity seemed to be particularly associated with descending colon cancer (RR = 2.4, P for trend <0.001). In women, the inverse association with activity was concentrated to proximal parts of colon; RR for cancer in the proximal and transverse colon among sedentary women was 1.4 and 2.0 (P for trend <0.07 and <0.01). Cancer of the rectum was not associated with activity in either sex. We confirmed the well-known inverse relationship between activity and risk of colon cancer but not rectal cancer in both sexes. Data suggest that the physical activity-related variation in risk among women is greatest in the proximal and middle parts of the colon, whereas the corresponding peak in men seems to be more distal. Sex-specific anatomic and motility differences of the colon might contribute to this subsite difference. C1 [Moradi, Tahereh] Karolinska Inst, Karolinska Hosp, Dept Publ Hlth Sci, Div Social Med, SE-17176 Stockholm, Sweden. [Moradi, Tahereh] Stockholm Cty Council, Stockholm, Sweden. [Bjork, Jan] Karolinska Univ Hosp, Gastroenterol & Hepatol Clin, Huddinge, Sweden. [Gridley, Gloria; Dosemeci, Mustafa; Ji, Bu-Tian] NCI, Div Epidemiol & Genet, Rockville, MD USA. [Berkel, Hans J.] Wright State Univ, Dayton, OH 45435 USA. [Lemeshow, Stanley] Ohio State Univ, Sch Publ Hlth, Columbus, OH 43210 USA. RP Moradi, T (reprint author), Karolinska Inst, Karolinska Hosp, Dept Publ Hlth Sci, Div Social Med, SE-17176 Stockholm, Sweden. EM Tahereh.moradi@ki.se FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N02-CP-7100] NR 63 TC 29 Z9 30 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 2008 VL 17 IS 3 BP 201 EP 208 PG 8 WC Oncology SC Oncology GA 294UR UT WOS:000255432300004 PM 18414190 ER PT J AU Waltz, P Chodick, G AF Waltz, Paul Chodick, Gabriel TI Assessment of ecological regression in the study of colon, breast, ovary, non-Hodgkin's lymphoma, or prostate cancer and residential UV SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE cancer incidence; ecologic studies; ecological study; ultraviolet ID VITAMIN-D; MORTALITY-RATES; SUNLIGHT; RADIATION; MELANOMA; EPIDEMIOLOGY; DIETARY; RISK; AGE AB Recent ecological studies have suggested a possible association between exposure to ultraviolet-B (UVB) radiation and reduction in the risk of various cancers; however, ecological studies are known to be subject to bias. The objective of this study was to demonstrate difficulties with the ecological approach. We conducted a multicountry ecological study using cancer incidence rates, residential UV levels, dietary intake, and different sociodemographic variables for 38 locations spanning 33 countries worldwide. The effect of residential UV exposure on cancer incidence was assessed using multiple linear regression models. The results of our multivariate analyses show no indication of an inverse association between residential UV levels and the risk of colon, non-Hodgkin's lymphoma (NHL), ovarian, prostate, or breast cancer in women. For colon cancer and NHL, a significant positive association was calculated. The rates of melanoma, which were used to examine the methods of this study, showed a strong and significant (P<0.01) association with solar radiation. Our results provide no evidence to support previous ecological results that UV exposure may reduce the risk of NHL, colon, breast, ovary, or prostate cancer. The study demonstrates the high sensitivity of ecological studies to adjustments for various confounders, and casts doubts on results of ecological analyses in this field. C1 [Waltz, Paul; Chodick, Gabriel] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Waltz, Paul; Chodick, Gabriel] Maccabi Hlth Serv, Tel Aviv, Israel. RP Chodick, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7049,MSC 7238, Bethesda, MD 20892 USA. EM hodik_g@mac.org.il NR 28 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 2008 VL 17 IS 3 BP 279 EP 286 DI 10.1097/CEJ.0b013e3282b6fd0f PG 8 WC Oncology SC Oncology GA 294UR UT WOS:000255432300015 PM 18414201 ER PT J AU Murphy, G Sansbury, LS Bergen, AW Wang, ZQ Schatzkin, A Lehman, T Kalidindi, A Modali, R Lanza, E AF Murphy, Gwen Sansbury, Leah S. Bergen, Andrew W. Wang, Zhuoqiao Schatzkin, Arthur Lehman, Teresa Kalidindi, Aravind Modali, Rama Lanza, Elaine TI Polynucleotide kinase 3 ' phosphatase variant, dietary variables and risk of adenoma recurrence in the Polyp Prevention Trial SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE adenoma; diet; DNA repair; polyp prevention trial ID PROSTATE-CANCER RISK; COLORECTAL-CANCER; GENE POLYMORPHISMS; ANTIOXIDANT INTAKE; XRCC1 GENE; REPAIR; SUSCEPTIBILITY; SMOKING; DESIGN; MODIFY AB Polymorphisms in a number of genes encoding for DNA repair enzymes have been associated with altering the function of these enzymes and increasing risk of a number of cancers, including colon cancer. We have investigated the association between a common variant in polynucleotide kinase 3' phosphatase (PNKP), a putative DNA repair enzyme, and risk of adenoma recurrence in the Polyp Prevention Trial participants. We also investigated possible interaction or effect modification between carriage of the variant allele, dietary components and risk of adenoma recurrence. Unconditional logistic regression models were used to calculate the odds ratios and 95% confidence intervals for an association between the G/T polymorphism, PNKP T5644G and risk of adenoma recurrence. We observed no association between carriage of the variant allele and risk of adenoma recurrence. Furthermore, we found no effect modification between genotype, dietary components and risk of adenoma recurrence. The PNKP T5644G variant does not seem to be involved in adenoma recurrence in the Polyp Prevention Trial. C1 [Murphy, Gwen; Bergen, Andrew W.; Schatzkin, Arthur] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Murphy, Gwen; Sansbury, Leah S.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Murphy, Gwen; Sansbury, Leah S.; Lanza, Elaine] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Wang, Zhuoqiao] Informat Management Serv Inc, Rockville, MD USA. [Lehman, Teresa; Kalidindi, Aravind; Modali, Rama] Bioserve Biotechnol Ltd, Laurel, MD USA. RP Murphy, G (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7067, Bethesda, MD 20892 USA. EM murphygw@mail.nih.gov OI Bergen, Andrew/0000-0002-1237-7644 FU Intramural NIH HHS NR 23 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 2008 VL 17 IS 3 BP 287 EP 290 DI 10.1097/CEJ.0b013e3282b6fdb8 PG 4 WC Oncology SC Oncology GA 294UR UT WOS:000255432300016 PM 18414202 ER PT J AU Horne, MK Merryman, P Cullinane, A Remaley, AT AF Horne, McDonald K., III Merryman, Paula Cullinane, Ann Remaley, Alan T. TI In vitro characterization of a monoclonal IgG(kappa) from a patient with planar xanthomatosis SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE xanthoma; monoclonal IgG(kappa) gammopathy of unknown significance; cryoprecipitate ID MULTIPLE-MYELOMA; BETA-LIPOPROTEIN; PHOSPHATIDYLCHOLINE; PHOSPHORYLCHOLINE; SPECIFICITY; GAMMOPATHY; PROTEINS AB Objective: To characterize a monoclonal IgG(kappa) (MAb) from a patient with planar xanthoma that precipitated with serum lipids at reduced temperature. Methods: The molecular weight (Mr), sensitivity to proteases, and glycosylation of the purified MAb were analyzed. The specificity of the MAb was tested by measuring cryoprecipitation with pure high- (HDL) and low-density (LDL) lipoproteins. The effect of choline, phosphocholine, and glycerol 3-phosphate on the precipitation temperature of LDL by the MAb was studied. Results: The MAb was larger than normal IgG due to hyperglycosylation of the MAb light chain. It formed cryoprecipitates with pure HDL and LDL as well as the lipids extracted from these lipoproteins. Fab fragments of the MAb lowered the temperature of its precipitation with LDL. Choline, phosphocholine, and glycerol 3-phosphate also lower the precipitation temperature. Conclusion: This is the first human IgG reported with apparent specificity for phosphocholine antigens. Its precipitation with lipids at reduced temperature suggests that it recognizes conformations of phospholipid head groups that develop below core body temperature. C1 [Horne, McDonald K., III; Merryman, Paula; Cullinane, Ann] NIH, WG Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. [Remaley, Alan T.] NIH, WG Magnuson Clin Ctr, Dept Lab Med, Chem Serv, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, WG Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mcdonald.horne@gmail.com FU Intramural NIH HHS NR 19 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUN PY 2008 VL 80 IS 6 BP 495 EP 502 DI 10.1111/j.1600-0609.2008.01072.x PG 8 WC Hematology SC Hematology GA 298QF UT WOS:000255701500006 PM 18363875 ER PT J AU Imamichi, H Sereti, I Lane, HC AF Imamichi, Hiromi Sereti, Irini Lane, H. Clifford TI IL-15 acts as a potent inducer of CD4(+)CD25(hi) cells expressing FOXP3 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokines; immune regulation; regulatory T cells; T cells ID REGULATORY T-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; HIV-INFECTED PATIENTS; INTERLEUKIN-2 RECEPTOR; LYMPHOID HOMEOSTASIS; PERIPHERAL-BLOOD; ALPHA-CHAIN; MICE; LYMPHOCYTES AB IL-15 is a member of they chain-dependent cytokines and known to affect innate and CD8(+) adaptive immune responses. Despite a growing interest in the use of IL-15 as an immunotherapeutic agent, the broad spectrum of immunoregulatory functions exerted by IL-15 has not been fully elucidated. Here, we demonstrate that IL-15 increases expression of CD25 and forkhead box transcription factor P3 (FOXP3), a master transcriptional regulator of regulatory T cells, in human peripheral CD4(+)CD25(-) T cells in the absence of antigenic stimulation. Comparisons involving IL-2 and IL-7 revealed that the induction of CD25(hi) and FOXP3 expression was most prominent with IL-15 and IL-2. More modest effects were seen with IL-7. Despite levels of FOXP3 expression comparable to that of conventional regulatory T cells, cytokine-induced CD4(+)CD25(hi)FOXP3(+) cells exerted only weak suppressor activity. Thus, the current study has demonstrated that IL-15 acts as a potent inducer of CD4(+)CD25(hi)FOXP3(+) cells in the periphery, and suggests a potential role for IL-15 in blunting immune activation. This study has provided further insights into the pleiotropic nature of IL-15 beyond the regulation of CD8(+) T cells. C1 [Imamichi, Hiromi] NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Sereti, Irini; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Imamichi, H (reprint author), NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, Bldg 550,Room 201-A,POB B, Frederick, MD 21702 USA. EM himamichi@nih.gov FU NCI NIH HHS [R44 CA124001, N01 CO012400, N01CO12400, R44 CA124001-04] NR 54 TC 42 Z9 44 U1 1 U2 2 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 JUN PY 2008 VL 38 IS 6 BP 1621 EP 1630 DI 10.1002/eji.200737607 PG 10 WC Immunology SC Immunology GA 313TH UT WOS:000256762400016 PM 18493981 ER PT J AU Epel, M Carmi, I Soueid-Baumgarten, S Oh, S Bera, T Pastan, I Berzofsky, J Reiter, Y AF Epel, Malka Carmi, Irit Soueid-Baumgarten, Sharon Oh, SangKon Bera, Tapan Pastan, Ira Berzofsky, Jay Reiter, Yoram TI Targeting TARP, a novel breast and prostate tumor-associated antigen, with T cell receptor-like human recombinant antibodies SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE immunotoxin; MHC; recombinant antibody; T-cell receptor ID COMPLEX-RESTRICTED SPECIFICITY; ALTERNATE READING FRAME; CANCER VACCINE TRIAL; IN-SITU DETECTION; MONOCLONAL-ANTIBODY; PHENOTYPIC ANALYSIS; ESCHERICHIA-COLI; PEPTIDE ANTIGENS; MEMBRANE ANTIGEN; FINE SPECIFICITY AB MHC class I molecules are important components of immune surveillance. There are no available methods to directly visualize and determine the quantity and distribution of MHC/peptide complexes on individual cells or to detect such complexes on antigen-presenting cells in tissues. MHC-restricted recombinant antibodies with the same specificity of T cell receptors (TCR) may become a valuable tool to address these questions. They may also serve as valuable targeting molecules that mimic the specificity of cytotoxic T cells. We isolated by phage display a panel of human recombinant Fab antibodies with peptide-specific, MHC-restricted TCR-like reactivity directed toward HLA-A2-restricted T cell epitopes derived from a novel antigen termed TCR gamma alternative reading frame protein (TARP) which is expressed on prostate and breast cancer cells. We have characterized one of these recombinant antibodies and demonstrated its capacity to directly detect specific HLA-A2/ TARP T cell epitopes on antigen-presenting cells that have complexes formed by naturally occurring active intracellular processing of the antigen, as well as on the surface of tumor cells. Moreover, by genetic fusion we armed the TCR-like antibody with a potent toxin and demonstrated that it can serve as a targeting moiety killing tumor cells in a peptide-specific, MHC-restricted manner similar to cytotoxic T lymphocytes. C1 [Epel, Malka; Carmi, Irit; Reiter, Yoram] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel. [Soueid-Baumgarten, Sharon] Technion Israel Inst Technol, Fac Med, IL-32000 Haifa, Israel. [Oh, SangKon; Berzofsky, Jay] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bera, Tapan; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Reiter, Y (reprint author), Technion Israel Inst Technol, Fac Biol, Room 333, IL-32000 Haifa, Israel. EM reiter@tx.technion.ac.il FU Intramural NIH HHS [Z01 BC010298-10] NR 70 TC 20 Z9 21 U1 1 U2 5 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 JUN PY 2008 VL 38 IS 6 BP 1706 EP 1720 DI 10.1002/eji.200737524 PG 15 WC Immunology SC Immunology GA 313TH UT WOS:000256762400024 PM 18446790 ER PT J AU Cai, LS Lu, SY Pike, VW AF Cai, Lisheng Lu, Shuiyu Pike, Victor W. TI Chemistry with [F-18]fluoride ion SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Review DE fluorine-18; [F-18]fluoride ion; PET; radiotracer; labeling ID POSITRON-EMISSION-TOMOGRAPHY; NUCLEOPHILIC AROMATIC-SUBSTITUTION; QUATERNARY 4-AMINOPYRIDINIUM RESIN; NICOTINIC ACETYLCHOLINE-RECEPTORS; HETEROAROMATIC IODONIUM SALTS; HIGH-AFFINITY RADIOLIGAND; ON-COLUMN PREPARATION; NO-CARRIER; F-18 FLUORIDE; HUMAN-BRAIN AB The success of molecular imaging with positron-emission tomography molecular probes labeled with positron-emitters, such as fluorine-18 (t(1/2) = 109.7 min). No-carrier-added (NCA) [F-18]fluoride ion (F-18(-)) is the primary reagent for the preparation of F-18-labeled tracers in high specific activity. In this microreview, we survey current and advancing radiochemical methods and technologies for the use of NCA [F-18]-fluoride ion in the preparation of F-18-labeled radiotracers for applications with PET. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008). C1 [Cai, Lisheng] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Cai, LS (reprint author), NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 183 TC 286 Z9 286 U1 8 U2 77 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1434-193X EI 1099-0690 J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD JUN PY 2008 IS 17 BP 2853 EP 2873 DI 10.1002/ejoc.200800114 PG 21 WC Chemistry, Organic SC Chemistry GA 317UG UT WOS:000257045000001 ER PT J AU Yucesoy, B Johnson, VJ Kissling, GE Fluharty, K Kashon, ML Slaven, J Germolec, D Vallyathan, V Luster, MI AF Yucesoy, B. Johnson, V. J. Kissling, G. E. Fluharty, K. Kashon, M. L. Slaven, J. Germolec, D. Vallyathan, V. Luster, M. I. TI Genetic susceptibility to progressive massive fibrosis in coal miners SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE coal miners; cytokines; polymorphism; progressive massive fibrosis ID TUMOR-NECROSIS-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; ENDOTHELIAL GROWTH-FACTOR; INDUCED PULMONARY-FIBROSIS; WORKERS PNEUMOCONIOSIS; FACTOR-ALPHA; POLYMORPHISMS; LUNG; EXPRESSION; ICAM-1 AB Progressive massive fibrosis (PMF) is a chronic interstitial lung disease with a complex aetiology that can occur after cumulative dust exposure. A case-control study was conducted to test the hypothesis that single nucleotide polymorphisms (SNPs) within genes involved in inflammatory and fibrotic processes modulate the risk of PMF development. The study population consisted of 648 underground coal miners participating in the National Coal Workers Autopsy Study, of which 304 were diagnosed with PMF SNPs that influence the regulation of interleukin (IL)-1, IL-6, tumour necrosis factor-alpha, transforming growth factor-beta 1, vascular endothelial growth factor (VEGF), epidermal growth factor intercellular cell adhesion molecule (ICAM)-1 and matrix metalloproteinase-2 genes were determined using a 5'-nuclease real-time PCR assay. There were no significant differences in the distribution of any individual SNP or haplotype between the PMF and control groups. However, the polygenotype of VEGF +405/ICAM-1 +241/IL-6 -174 (C-A-G) conferred an increased risk for PMF (odds ratio 3.4, 95% confidence interval 1.3-8.8). The present study suggests that the examined genetic variations that help regulate inflammatory and fibrotic processes are unlikely to strongly influence susceptibility to this interstitial lung disease, although the role of vascular endothelial growth factor, intercellular cell adhesion molecule-1 and interleukin-6 polymorphisms in the development of progressive massive fibrosis may require further investigation. C1 [Yucesoy, B.; Johnson, V. J.; Fluharty, K.; Luster, M. I.] NIOSH, Toxicol & Mol Biol Branch, Hlth Effects Lab Div, CDC, Morgantown, WV 26505 USA. [Kashon, M. L.; Slaven, J.] NIOSH, Biostat & Epidemiol Branch, CDC, Morgantown, WV 26505 USA. [Vallyathan, V.] NIOSH, Pathol & Physiol Res Branch, CDC, Morgantown, WV 26505 USA. [Kissling, G. E.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. [Germolec, D.] Natl Inst Environm Hlth Sci, Toxicol Operat Branch, Res Triangle Pk, NC USA. RP Yucesoy, B (reprint author), NIOSH, Toxicol & Mol Biol Branch, Hlth Effects Lab Div, CDC, 1095 Willowdale Rd, Morgantown, WV 26505 USA. EM byucesoy@cdc.gov RI Johnson, Victor/A-7910-2009; Yucesoy, Berran/B-4497-2009 FU Intramural NIH HHS NR 34 TC 9 Z9 14 U1 1 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUN PY 2008 VL 31 IS 6 BP 1177 EP 1182 DI 10.1183/09031936.00075107 PG 6 WC Respiratory System SC Respiratory System GA 312XM UT WOS:000256705700008 PM 18256065 ER PT J AU Song, J Liu, H Ressom, HW Tiwari, S Ecelbarger, CM AF Song, J. Liu, H. Ressom, H. W. Tiwari, S. Ecelbarger, C. M. TI Chronic rosiglitazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray analysis SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE thiazolidinediones; PPAR-gamma agonists; renal; type II diabetes; obesity ID ACTIVATED-RECEPTOR-GAMMA; LOWERS BLOOD-PRESSURE; NA-CL COTRANSPORTER; PULMONARY-EDEMA; ANGIOTENSIN-II; PPAR-GAMMA; INSULIN SENSITIZERS; MEDIATED REGULATION; DIABETIC-RATS; UP-REGULATION AB Thiazolidinediones increase tissue insulin sensitivity and are protective against worsening of nephropathy and hypertension in diabetes. Mechanisms underlying protection at the renal level likely involve a variety of unknown changes ingene expression. We examined kidney gene expression in obese and lean Zucker rats in response to rosiglitazone (Avandia (R)), a peroxisome proliferator activated receptor (T-subtype) agonist. Lean and obese Zucker rats were treated with either control chow or chow with added rosiglitazone (3mg/kg.bw) for 12 weeks (n=3/group). Total kidney mRNA expression was evaluated using the Affymetrix Rat Genome 230 2.0 GeneChip. 903 probe sets were significantly (P<0.05) altered with at least 1.5-fold changes between groups. In untreated obese rats, 300 probe sets were increased and 244 decreased, relative to lean. increased genes included the beta-subunit of the epithelial sodium channel (ENaC), the thiazidesensitive Na-Cl cotransporter, and aquaporin 3. Decreased genes included angiotensin converting enzyme, type 1 (ACE1). FatiGO analysis showed that the highest number of altered genes between lean and obese belonged to the categories: ion binding, hydrolase activity, and protein binding. RGZ increased expression of uncoupling protein 1 (UCP1), CD36, and fatty acid binding protein 4 (FAbp4) in both lean and obese rats. In obese rats, 33 genes were normalized by RGZ (no longer different from lean) including ACE1, fatty acid synthase (Fasn), and stearoyl-coenzyme A desaturase (SCD1). Ingenuity Pathways System analysis of genes upregulated by RGZ in obese rats revealed two major nodes affected: PPAR-gamma and tumor necrosis factor alpha (TNF-alpha). C1 [Song, J.; Tiwari, S.; Ecelbarger, C. M.] Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC USA. [Liu, H.] Natl Canc Inst, Ctr Bioinformat, Sci Applicat Int Corp, NIH, Rockville, MD USA. [Ressom, H. W.] Georgetown Univ, Lombardi Comprehensive Canc Ctr, Washington, DC USA. RP Ecelbarger, CM (reprint author), Bldg D,Rm 233,4000 Reservoirr Rd NW, Washington, DC 20057 USA. EM ecelbarc@georgetown.edu FU NHLBI NIH HHS [R01 HL073193, HL073193, HL074142]; NIDDK NIH HHS [DK064872] NR 51 TC 10 Z9 10 U1 0 U2 2 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD JUN PY 2008 VL 116 IS 6 BP 315 EP 325 DI 10.1055/s-2008-1042429 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 320PA UT WOS:000257245900002 PM 18700276 ER PT J AU Knutson, KM McClellan, EM Grafman, J AF Knutson, Kristine M. McClellan, Erin M. Grafman, Jordan TI Observing social gestures: an fMRI study SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE functional MRI; social psychology; gestures ID EVENT-RELATED FMRI; HUMAN EXTRASTRIATE CORTEX; SUPERIOR TEMPORAL SULCUS; PREMOTOR CORTEX; HUMAN AMYGDALA; FACIAL EXPRESSIONS; PREFRONTAL CORTEX; FACE PERCEPTION; BRAIN; ACTIVATION AB We investigated the effects of social content of gestures on brain activation patterns. We used a 3 x 3 x 3 factorial design in an event-related functional magnetic resonance imaging experiment with participants observing gestures varied by type (fascist salute, wave, or arm lift), number of images shown at a time, and face frequency. We sought to determine whether increasing the social content of the gesture spreads activation from traditional sensorimotor regions engaged in mirror neuron activity to prefrontal regions concerned with social behavior. Results indicate that viewing a highly provocative gesture (fascist salute) compared to a less provocative but still socially meaningful gesture (wave) reveals activation in prefrontal and limbic areas. In addition, as expected there was more inferior frontal gyrus activation when participants observed a greater number of gesturing actors. Additionally, the psychological characteristics of shame and defeat affected activation in the inferior parietal lobe, which is part of the mirror neuron system, for the fascist salute compared to the wave contrast. We conclude that observing social gestures activates social- and emotion-processing areas of the brain, and the activation varies depending on the observer's psychological characteristics. C1 [Knutson, Kristine M.; McClellan, Erin M.; Grafman, Jordan] Natl Inst Neurol Disorders & Sroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Sroke, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440,10 Ctr Dr, Bethesda, MD 20892 USA. EM knutsonk@ninds.nih.gov; grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457; Knutson, Kristine/0000-0003-4626-4514 FU Intramural NIH HHS NR 77 TC 16 Z9 16 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2008 VL 188 IS 2 BP 187 EP 198 DI 10.1007/s00221-008-1352-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 313QO UT WOS:000256755300003 PM 18483724 ER PT J AU Kissler, J Keil, A AF Kissler, Johanna Keil, Andreas TI Look-don't look! How emotional pictures affect pro- and anti-saccades SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE emotion; eye movement; anti-saccade; pro-saccade; superior colliculus ID EYE-MOVEMENT; SUPERIOR COLLICULUS; FACIAL EXPRESSIONS; AROUSAL; PERCEPTION; RESPONSES; SALIENCE; TASK; MAP AB We investigated the effect of emotional target content on the generation of pro- and anti-saccades. Subjects had to generate saccades towards (pro-saccade) or away from (anti-saccade) peripherally presented pleasant, unpleasant or neutral pictures. Two different SOAs were used, either with simultaneous fixation offset and target onset (no gap) or with fixation offset preceding target onset by 200 ms (gap). In the pro-saccade task participants were faster to respond to emotional pictures in the left visual field. In the right visual field facilitation occurred only for pleasant pictures and saccadic reaction times towards unpleasant pictures were slowed. In the anti-saccade task more anti-saccade errors towards emotional pictures (pleasant and unpleasant) were made in the gap condition. On the whole, endogenous saccade generation appears facilitated by emotional target content, probably via increased input from extra-striate and parietal brain areas to the superior colliculus. Moderating factors such as the SOA or the visual field of presentation are discussed. C1 [Kissler, Johanna] Univ Konstanz, Dept Psychol, D-78457 Constance, Germany. [Keil, Andreas] Univ Florida, Dept Psychol, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. RP Kissler, J (reprint author), Univ Konstanz, Dept Psychol, Box D 25, D-78457 Constance, Germany. EM Johanna.Kissler@uni-konstanz.de RI Keil, Andreas/F-9427-2011 OI Keil, Andreas/0000-0002-4064-1924 NR 28 TC 33 Z9 35 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2008 VL 188 IS 2 BP 215 EP 222 DI 10.1007/s00221-008-1358-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 313QO UT WOS:000256755300005 PM 18368396 ER PT J AU Scheidemann, F Loser, M Niedermeier, A Kromminga, A Therrien, JP Vogel, J Pfurtzner, W AF Scheidemann, Frank Loeser, Maria Niedermeier, Andrea Kromminga, Arno Therrien, Jean-Philippe Vogel, Jon Pfuertzner, Wolfgang TI The skin as a biofactory for systemic secretion of erythropoietin: potential of genetically modified keratinocytes and fibroblasts SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE erythropoietin; fibroblast; gene therapy; keratinocyte; skin equivalent ID QUALITY-OF-LIFE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; MULTIDRUG-RESISTANCE GENE; EXPRESSION IN-VIVO; EPIDERMAL-KERATINOCYTES; EPOETIN-ALPHA; TARGET-CELLS; THERAPY; CHEMOTHERAPY; DELIVERY AB Background: The skin is an interesting target tissue for gene therapy applications because of its ready accessibility. One possibility would be to utilize the genetically modified skin as a biofactory secreting a systemically needed product, such as erythropoietin (EPO). Methods: Keratinocytes (KC) and fibroblasts (FB) were transduced with a retroviral vector encoding human EPO. Gene transfer efficiency was assessed by real-time PCR analysis and flow cytometry of transduced cells. In addition, EPO synthesis and secretion were analysed by quantifying the amount of RNA and secreted protein in both monolayer cultures and skin equivalents (SE). Results: When cultured as a monolayer, EPO-KC synthesized significantly more EPO than EPO-FB, as shown by quantitatively measuring the amount of secreted protein and RNA. This correlated with an increased EPO-vector incorporation in KC compared with FB, demonstrated by determining both the percentage of transduced cells and the average transgene copy number per cell. In addition, in transduced cell cultures enriched to equally high percentages of EPO+ cells, KC showed a higher activity of EPO secretion than FB. Finally, when assembled in a SE, EPO-KC secreted significantly higher amounts of EPO than EPO-FB, although reduced secretory activity of EPO-KC monolayers grown in high calcium concentrations suggested that in stratified epidermis differentiated KC secrete less EPO than non-differentiated KC. Conclusion: In summary, while both transduced KC and FB are able to synthesize and secrete human EPO, KC show higher potential in serving as possible target cells for therapeutic substitution with EPO, probably because of improved transduction rates and increased secretory activity. C1 [Pfuertzner, Wolfgang] Univ Hosp, Dept Dermatol & Allergol, DE-35033 Marburg, Germany. [Scheidemann, Frank; Loeser, Maria; Niedermeier, Andrea] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. [Kromminga, Arno] Inst Immunol Clin Pathol Mol Med, Hamburg, Germany. [Therrien, Jean-Philippe; Vogel, Jon] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Pfurtzner, W (reprint author), Univ Hosp, Dept Dermatol & Allergol, Deutschhaus Str 9, DE-35033 Marburg, Germany. EM wolfgang_pfutzner@web.de NR 50 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JUN PY 2008 VL 17 IS 6 BP 481 EP 488 DI 10.1111/j.1600-0625.2007.00680.x PG 8 WC Dermatology SC Dermatology GA 298QX UT WOS:000255703300002 PM 18331333 ER PT J AU Chen, J Volpi, S Aguilera, G AF Chen, Jun Volpi, Simona Aguilera, Greti TI Anti-apoptotic actions of vasopressin in H32 neurons involve map kinase transactivation and bad phosphorylation SO EXPERIMENTAL NEUROLOGY LA English DT Article DE vasopressin; V1a receptor; apoptosis; MAPK/ERK; bad; RSK ID CORTICOTROPIN-RELEASING FACTOR; EPIDERMAL GROWTH-FACTOR; C-INDUCED APOPTOSIS; CELL-DEATH; PARAVENTRICULAR NUCLEUS; DEPENDENT MECHANISM; SIGNAL-TRANSDUCTION; BINDING PROTEIN; MESSENGER-RNA; V1A RECEPTOR AB Vasopressin (VP) secreted within the brain modulates neuronal function acting as a neurotransmitter. Based on the observation that VP prevented serum deprivation-induced cell death in the neuronal cell line, H32, which expresses endogenous VI receptors, we tested the hypothesis that VP has anti-apoptotic properties. Flow cytometry experiments showed that 10 nM VP prevented serum deprivation-induced cell death and annexin V binding. Serum deprivation increased caspase-3 activity in a time and serum concentration dependent manner, and VP prevented these effects through interaction with receptors of VI subtype. The signaling pathways mediating the anti-apoptotic effect of VP involve mitogen activated protein (MAP) kinase and extracellular signal-regulated kinases (ERK), Ca2+/calmodulin dependent kinase (CaMK) and protein kinase C (PKC). Western blot analyses revealed time-dependent decreases of Bad phosphorylation and increases in cytosolic levels of cytochrome c following serum deprivation, effects which were prevented by 10 nM VP. These data demonstrate that activation of endogenous V1 VP receptors prevents serum deprivation-induced apoptosis, through phosphorylation-inactivation of the pro-apoptotic protein, Bad, and consequent decreases in cytosolic cytochrome c and caspase-3 activation. The data suggest that VP has anti-apoptotic activity in neurons and that VP may act as a neuroprotective agent in the brain. Published by Elsevier Inc. C1 [Chen, Jun; Volpi, Simona; Aguilera, Greti] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Room 1E-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM Greti_Aguilera@nih.gov FU Intramural NIH HHS [Z01 HD008813-01, Z01 HD000631-18, Z99 HD999999] NR 47 TC 13 Z9 14 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2008 VL 211 IS 2 BP 529 EP 538 DI 10.1016/j.expneurol.2008.02.023 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 306UH UT WOS:000256272800027 PM 18402937 ER PT J AU Ambrosino, E Berzofsky, JA Terabe, M AF Ambrosino, Elena Berzofsky, Jay A. Terabe, Masaki TI Regulation of tumor immunity: the role of NKT cells SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE immunoregulation; NKT cells; tumor immunity; tumor immunology; tumor immunosurveillance ID KILLER-T-CELLS; ALPHA-GALACTOSYLCERAMIDE KRN7000; NATURAL-KILLER; IFN-GAMMA; IN-VIVO; ANTITUMOR IMMUNITY; PHASE-I; AIRWAY HYPERREACTIVITY; MEDIATED CYTOTOXICITY; COLORECTAL-CANCER AB Background: Tumor immunosurveillance is a part of the dynamic process of interaction between abnormal cells and the host immune system. Tumor immunosurveillance is actively and continuously regulated in both positive and negative ways. Natural killer T (NKT) cells are cells that have been shown to play a role in both positive and negative regulation of tumor immunosurveillance. Recent studies suggest that NKT cells are a heterogeneous cell population with multiple subsets with distinct functions. Objective: This review discusses the functions of those NKT cell subsets in regulating tumor immunity and potential interactions or counter-regulation among the NKT cell subsets. Method: Selected literature is reviewed. Conclusion: Manipulation of the balance among those subsets may provide new modes of intervention for tumor immunotherapy. C1 [Ambrosino, Elena; Berzofsky, Jay A.; Terabe, Masaki] NCI, Ctr Canc Res, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch,NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Ctr Canc Res, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch,NIH, Bldg 10,Room 6B12,9000 Rockville Pike, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov FU Intramural NIH HHS NR 136 TC 22 Z9 23 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUN PY 2008 VL 8 IS 6 BP 725 EP 734 DI 10.1517/14712590802085622 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 311BI UT WOS:000256574600004 PM 18476784 ER PT J AU Pfaffenroth, EC Linehan, WM AF Pfaffenroth, Elizabeth Cartwright Linehan, W. Marston TI Genetic basis for kidney cancer: opportunity for disease-specific approaches to therapy SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE Birt-Hogg-Dube; fumarate hydratase; hereditary leiomyomatosis renal cell carcinoma; hereditary papillary renal cancer; kidney cancer; Met; renal cell carcinoma; Von Hippel-Lindau ID HOGG-DUBE-SYNDROME; RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU-DISEASE; PARENCHYMAL SPARING SURGERY; GENOTYPE-PHENOTYPE CORRELATION; HEREDITARY LEIOMYOMATOSIS; FUMARATE-HYDRATASE; MET PROTOONCOGENE; SPONTANEOUS PNEUMOTHORAX AB Background: Kidney cancer is not a homogenous entity; it is comprised of many different tumor types, with different biologies and molecular mechanisms leading to disease and therefore different treatment approaches. Objective: To describe the genetic basis and biochemical pathways underlying inherited forms of renal cancer, specifically in four described syndromes (von Hippel-Lindau [VHL], hereditary papillary renal cancer [HPRC], Birt-Hogg-Dube [BHD] and hereditary leiomyomatosis renal cell carcinoma [HLRCC]), and to elucidate how the understanding of these diseases enables the possibility of disease-specific approaches to therapy. Methods: A systematic review of the published literature on inherited and sporadic forms of renal cancer was performed. Conclusion: Understanding of the biology and mechanisms of different forms of kidney cancer provides an opportunity for development of new treatment options. C1 [Pfaffenroth, Elizabeth Cartwright; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr,MSC 1107,Bldg 10,CRC Room 1-5942, Bethesda, MD 20892 USA. EM WML@nih.gov; pfaffee@mail.nih.gov FU Intramural NIH HHS [Z01 SC006659-25] NR 90 TC 34 Z9 34 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUN PY 2008 VL 8 IS 6 BP 779 EP 790 DI 10.1517/14712590802085663 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 311BI UT WOS:000256574600009 PM 18476789 ER PT J AU Christ-Crain, M Kola, B Lolli, F Fekete, C Seboek, D Wittmann, G Feltrin, D Igreja, SC Ajodha, S Harvey-White, J Kunos, G Mueller, B Pralong, F Aubert, G Arnaldi, G Giacchetti, G Boscaro, M Grossman, AB Korbonits, M AF Christ-Crain, Mirjam Kola, Blerina Lolli, Francesca Fekete, Csaba Seboek, Dalma Wittmann, Gabor Feltrin, Daniel Igreja, Susana C. Ajodha, Sharon Harvey-White, Judith Kunos, George Mueller, Beat Pralong, Francois Aubert, Gregory Arnaldi, Giorgio Giacchetti, Gilberta Boscaro, Marco Grossman, Ashley B. Korbonits, Marta TI AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome SO FASEB JOURNAL LA English DT Article DE obesity; insulin resistance; lipid metabolism ID HUMAN ADIPOSE-TISSUE; FATTY-ACID OXIDATION; CARDIOVASCULAR RISK; FOOD-INTAKE; ENDOCANNABINOID RELEASE; HYPOTHALAMIC NEURONS; ORAL CORTICOSTEROIDS; HUMAN ADIPOCYTES; GLUCOSE-UPTAKE; INSULIN AB Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid- excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess. C1 [Christ-Crain, Mirjam; Kola, Blerina; Lolli, Francesca; Feltrin, Daniel; Igreja, Susana C.; Ajodha, Sharon; Grossman, Ashley B.; Korbonits, Marta] Univ London, Queen Marys Sch Med, William Harvey Res Inst, John Vane Sci Ctr,Dept Endocrinol, London EC1M 6BQ, England. [Fekete, Csaba; Wittmann, Gabor] Hungarian Acad Sci, Inst Expt Med, Dept Endocrine Neurobiol, Budapest, Hungary. [Fekete, Csaba; Wittmann, Gabor] Tufts Univ New England Med Ctr, Div Endocrinol Diabet Metab & Mol Med, Tupper Res Inst, Boston, MA USA. [Fekete, Csaba; Wittmann, Gabor] Tufts Univ New England Med Ctr, Div Endocrinol Diabet Metab & Mol Med, Dept Med, Boston, MA USA. [Seboek, Dalma] Univ Basel Hosp, Div Endocrinol Diabet & Clin Nutr, CH-4031 Basel, Switzerland. [Harvey-White, Judith; Kunos, George] NIAAA, Lab Physiol Studies, US Natl Inst Hlth, Bethesda, MD USA. [Pralong, Francois; Aubert, Gregory] CHU Vaudois, Dept Internal Med, Serv Endocrinol Diabetol & Metab, CH-1011 Lausanne, Switzerland. [Arnaldi, Giorgio; Giacchetti, Gilberta; Boscaro, Marco] Univ Ancona, Dept Internal Med, Ancona, Italy. RP Korbonits, M (reprint author), Univ London, Queen Marys Sch Med, William Harvey Res Inst, John Vane Sci Ctr,Dept Endocrinol, London EC1M 6BQ, England. EM m.korbonits@qmul.ac.uk OI igreja, susana/0000-0003-2811-4766; BOSCARO, MARCO/0000-0003-2596-1652; Fekete, Csaba/0000-0002-8206-562X; Korbonits, Marta/0000-0002-4101-9432 FU Wellcome Trust NR 59 TC 74 Z9 76 U1 1 U2 7 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 JUN PY 2008 VL 22 IS 6 BP 1672 EP 1683 DI 10.1096/fj.07-094144 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307XK UT WOS:000256352700008 PM 18198220 ER PT J AU Grumolato, L Ghzili, H Montero-Hadjadje, M Gasman, S Lesage, J Tanguy, Y Galas, L Ait-Ali, D Leprince, J Guerineau, NC Elkahloun, AG Fournier, A Vieau, D Vaudry, H Anouar, Y AF Grumolato, Luca Ghzili, Hafida Montero-Hadjadje, Maite Gasman, Stephane Lesage, Jean Tanguy, Yannick Galas, Ludovic Ait-Ali, Djida Leprince, Jerome Guerineau, Nathalie C. Elkahloun, Abdel G. Fournier, Alain Vieau, Didier Vaudry, Hubert Anouar, Youssef TI Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca(2+) mobilization and neuroendocrine secretion SO FASEB JOURNAL LA English DT Article DE cell differentiation; pituitary adenylate cyclase-activating polypeptide; cAMP; PC12 cells ID CYCLASE-ACTIVATING POLYPEPTIDE; NERVE GROWTH-FACTOR; PC12 CELLS; SYMPATHOADRENAL LINEAGE; PHEOCHROMOCYTOMA CELLS; ENDOPLASMIC-RETICULUM; MUSCULAR-DYSTROPHY; SIGNALING PATHWAYS; NEURITE OUTGROWTH; NEUROPEPTIDE-Y AB Selenoproteins contain the essential trace element selenium, the deficiency of which is associated with cancer or accelerated aging. Although selenoproteins are thought to be instrumental for the effects of selenium, the biological function of many of these proteins remains unknown. Here, we studied the role of selenoprotein T (SelT), a selenocysteine (Sec)-containing protein with no known function, which we have identified as a novel target gene of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) during PC12 cell differentiation. SelT was found to be ubiquitously expressed throughout embryonic development and in adulthood in rat. Immunocytochemical analysis revealed that SelT is mainly localized to the endoplasmic reticulum through a hydrophobic domain. PACAP and cAMP induced a rapid and long-lasting increase in SelT gene expression in PC12 cells, in a Ca(2+)-dependent manner. These results suggested a possible role of SelT in PACAP signaling during PC12 cell differentiation. Indeed, overexpression of SelT in PC12 cells provoked an increase in the concentration of intracellular Ca(2+) ([Ca(2+)](i)) that was dependent on the Sec residue. Conversely, SelT gene knockdown inhibited the PACAP-induced increase in [Ca(2+)] i and reduced hormone secretion. These findings demonstrate the implication of a selenoprotein in the regulation of Ca(2+) homeostasis and neuroendocrine secretion in response to a cAMP-stimulating trophic factor. C1 [Grumolato, Luca; Ghzili, Hafida; Montero-Hadjadje, Maite; Tanguy, Yannick; Galas, Ludovic; Ait-Ali, Djida; Leprince, Jerome; Vaudry, Hubert; Anouar, Youssef] Univ Rouen, INSERM, Lab Cellular & Mol Neuroendocrinol, CNRS,European Inst Peptide Res,IFRMP 23,UA,U413, F-76821 Mont St Aignan, France. [Gasman, Stephane] Univ Strasbourg 1, CNRS, Inst Neurosci Cellulaires & Integrat,LC2, Dept Neurotransmiss & Neuroendocrine Secret,UMR 7, Strasbourg, France. [Lesage, Jean] Univ Lille 1, Perinatal Stress Unit, Dept Adaptat Neurosci & Physiol, F-59655 Villeneuve Dascq, France. [Guerineau, Nathalie C.] Univ Montpellier 1, CNRS, INSERM, Funct Genom Inst,Dept Endocrinol,UMR5203,U661, Montpellier, France. [Guerineau, Nathalie C.] Univ Montpellier 2, Montpellier, France. [Elkahloun, Abdel G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Fournier, Alain] Univ Quebec, Inst Natl Rech Sci, Inst Armand Frappier, Montreal, PQ H3C 3P8, Canada. RP Anouar, Y (reprint author), Univ Rouen, INSERM, Lab Cellular & Mol Neuroendocrinol, CNRS,European Inst Peptide Res,IFRMP 23,UA,U413, F-76821 Mont St Aignan, France. EM youssef.anouar@univ-rouen.fr RI galas, ludovic/A-2500-2014; Grumolato, Luca/A-1697-2015; Gasman, Stephane/D-5113-2017; OI Grumolato, Luca/0000-0001-8231-3032; Gasman, Stephane/0000-0001-8415-1276; Guerineau, Nathalie/0000-0003-2517-4210 NR 50 TC 56 Z9 60 U1 0 U2 11 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 JUN PY 2008 VL 22 IS 6 BP 1756 EP 1768 DI 10.1096/fj.06-075820 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307XK UT WOS:000256352700016 PM 18198219 ER PT J AU Tan, WF Palmby, TR Gavard, J Amornphimoltham, P Zheng, Y Gutkind, JS AF Tan, Wenfu Palmby, Todd R. Gavard, Julie Amornphimoltham, Panomwat Zheng, Yi Gutkind, J. Silvio TI An essential role for Rac1 in endothelial cell function and vascular development SO FASEB JOURNAL LA English DT Article DE angiogenesis; S1P; VEGF; migration; cytoskeleton ID IN-VIVO; TRANSGENIC MICE; ANGIOGENESIS; RHO; MIGRATION; ADHESION; GROWTH; VEGF; SPHINGOSINE-1-PHOSPHATE; VASCULOGENESIS AB Numerous cell surface receptors, including tyrosine kinase and G protein-coupled receptors, play critical roles in endothelial cell function and blood vessel development. These receptors share the ability of stimulating an intricate network of intracellular signaling pathways, including the activation of members of the Ras and Rho family of small GTPases. However, the contribution of these signaling molecules to the numerous biological activities performed by endothelial cells is still not fully understood. Here, we have used a conditional Cre/ Flox approach, enabling the deletion of the Rac1 gene in endothelial cells, to examine the role of the Rho-related GTPase Rac1 in endothelial cell function and vascular development. Rac1 excision in primary endothelial cells in vitro revealed that Rac1 plays a central role in endothelial cell migration, tubulogenesis, adhesion, and permeability in response to vascular endothelial growth factor (VEGF) and sphingosine-1-phosphate (S1P), which is likely due to the inability of Rac1-deficient endothelial cells to form lamellipodial structures and focal adhesions, and to remodel their cell-cell contacts. Importantly, endothelial-specific excision of Rac1 results in embryonic lethality in midgestation (around E9.5), and defective development of major vessels and complete lack of small branched vessels was readily observed in these endothelial Rac1-deficient embryos and their yolk sacs. These findings provide direct evidence that the activity of Rac1 in endothelial cells is essential for vascular development and suggest that Rac1 and its downstream targets may represent promising therapeutic targets for the treatment of numerous human diseases that involve aberrant neovascularization. C1 [Tan, Wenfu; Palmby, Todd R.; Gavard, Julie; Amornphimoltham, Panomwat; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Zheng, Yi] Univ Cincinnati, Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012; Zheng, Yi/J-7235-2015 OI Gavard, Julie/0000-0002-7985-9007; Zheng, Yi/0000-0001-7089-6074 FU Intramural NIH HHS NR 42 TC 120 Z9 125 U1 1 U2 9 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 JUN PY 2008 VL 22 IS 6 BP 1829 EP 1838 DI 10.1096/fj.07-096438 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307XK UT WOS:000256352700023 PM 18245172 ER PT J AU Misteli, T AF Misteli, T. TI Genome organization in the formation of cancer translocations and DNA repair SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Misteli, T.] Natl Canc Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 4 EP 4 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300013 ER PT J AU Earnshaw, WC Nakano, M Cardinale, S Noskov, VN Gassmann, R Vagnarelli, P Kandels-Lewis, S Larionov, V Masumoto, H AF Earnshaw, W. C. Nakano, M. Cardinale, S. Noskov, V. N. Gassmann, R. Vagnarelli, P. Kandels-Lewis, S. Larionov, V. Masumoto, H. TI Mapping the epigenetic landscape of the kinetochore SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Earnshaw, W. C.; Cardinale, S.; Gassmann, R.; Vagnarelli, P.; Kandels-Lewis, S.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. [Nakano, M.; Noskov, V. N.; Larionov, V.; Masumoto, H.] NCI, NIH, Bethesda, MD 20892 USA. [Masumoto, H.] Nagoya Univ, Div Biol Sci, Nagoya, Aichi 4648601, Japan. RI Cardinale, Stefano/F-4024-2014 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 JUN PY 2008 VL 275 SU 1 BP 7 EP 7 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300021 ER PT J AU Cidlowski, JA Lu, NZ Beckley, A Jewel, CM Revollo, J Schoneveld, O Duma, D Gross, K Ren, R Oakley, RH AF Cidlowski, J. A. Lu, N. Z. Beckley, A. Jewel, C. M. Revollo, J. Schoneveld, O. Duma, D. Gross, K. Ren, R. Oakley, R. H. TI The Glucocorticoid Receptor: one gene, many proteins - new mechanisms for tissue specific anti-inflammatory actions of glucocorticoids in health and disease SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Cidlowski, J. A.; Lu, N. Z.; Beckley, A.; Jewel, C. M.; Revollo, J.; Schoneveld, O.; Duma, D.; Gross, K.; Ren, R.; Oakley, R. H.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 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 JUN PY 2008 VL 275 SU 1 BP 15 EP 15 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300048 ER PT J AU Hinnebusch, A AF Hinnebusch, A. TI In vivo functions of translation factors and rRNA in initiation complex assembly and AUG recognition SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Hinnebusch, A.] NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 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 JUN PY 2008 VL 275 SU 1 BP 17 EP 17 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300053 ER PT J AU Cheng, SY AF Cheng, S. -Y. TI Novel non-genomic signaling of thyroid hormone receptors in thyroid carcinogenesis SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Cheng, S. -Y.] NCI, NIH, Bethesda, MD 20892 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 JUN PY 2008 VL 275 SU 1 BP 59 EP 59 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300161 ER PT J AU Soldatov, NM Kobrinsky, E AF Soldatov, N. M. Kobrinsky, E. TI CREB-dependent transcriptional activation signals are caged in calmodulin, transferred by moving Ca(v)1.2 calcium channel tail, and occur in discrete nuclear microdomains SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Soldatov, N. M.; Kobrinsky, E.] NIA, NIH, Baltimore, MD 21224 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 JUN PY 2008 VL 275 SU 1 BP 94 EP 94 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300246 ER PT J AU Hwang, JY Sasaki, N Kolonder, R Myung, K AF Hwang, J. -Y. Sasaki, N. Kolonder, R. Myung, K. TI Human PIF1 suppresses genomic instability through its evolutionary conserved role in telomere maintenance Poster presentations SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Hwang, J. -Y.] Korean German Inst Technol, Biotechnol Res Ctr, Cell Biol Team, Seoul, South Korea. [Sasaki, N.] Hokkaido Univ, Grad Sch Vet Med, Lab Expt Anim Sci, Sapporo, Hokkaido, Japan. [Kolonder, R.] Univ Calif San Diego, Ctr Canc, Ludwig Inst Canc Res, San Diego Sch Med, La Jolla, CA 92093 USA. [Kolonder, R.] Univ Calif San Diego, Dept Med, San Diego Sch Med, La Jolla, CA 92093 USA. [Myung, K.] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 275 SU 1 BP 99 EP 99 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300258 ER PT J AU Salpea, P Russanova, VR Sekeri-Pataryas, K Howard, BH Sourlingas, TG AF Salpea, P. Russanova, V. R. Sekeri-Pataryas, K. Howard, B. H. Sourlingas, T. G. TI Age-related changes at the histone H10 gene region SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Salpea, P.; Sekeri-Pataryas, K.; Sourlingas, T. G.] Natl Ctr Sci Res Demokritos, Inst Biol, Lab Histone Biochem & Ageing, Athens, Greece. [Russanova, V. R.; Howard, B. H.] NICHHD, NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RI Salpea, Paraskevi/A-8027-2010 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 JUN PY 2008 VL 275 SU 1 BP 105 EP 105 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300279 ER PT J AU Balatsos, NAA Fragkos-Livanios, L Xiao, Z Veenstra, TD Panayotou, G Rogakou, EP AF Balatsos, N. A. A. Fragkos-Livanios, L. Xiao, Z. Veenstra, T. D. Panayotou, G. Rogakou, E. P. TI H2AX and lamin A/C interact dynamically in apoptosis indicating the existence of H2AX-organized machinery centers SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Balatsos, N. A. A.] Univ Thessaly, Dept Biochem & Biotechnol, Larisa, Greece. [Fragkos-Livanios, L.; Panayotou, G.; Rogakou, E. P.] BSRC AR Fleming, Inst Mol Oncol, Larisa, Greece. [Xiao, Z.; Veenstra, T. D.] NCI, NIH, SAIC Frederick Inc, Lab Prote & Analyt Technol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 107 EP 107 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300284 ER PT J AU Hwang, JY Smith, S Torres-Rosell, J Aragon, L Myung, K AF Hwang, J. -Y. Smith, S. Torres-Rosell, J. Aragon, Luis Myung, K. TI Smc5-Smc6 regulate gross chromosomal rearrangements and mediate DNA double-strand-break repair SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE ID SACCHAROMYCES-CEREVISIAE C1 [Hwang, J. -Y.] KGIT Sangam Ctr, Biotechnol Res Ctr, Cell Biol Team, Seoul, South Korea. [Smith, S.; Myung, K.] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Torres-Rosell, J.; Aragon, Luis] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, Cell Cycle Grp, London, England. RI Torres-Rosell, Jordi/A-4213-2010 OI Torres-Rosell, Jordi/0000-0003-1308-6926 NR 3 TC 1 Z9 1 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 JUN PY 2008 VL 275 SU 1 BP 113 EP 113 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300305 ER PT J AU Fragkos-Livanios, L Balatsos, NAA Xiao, Z Veenstra, TD Panayotou, G Rogakou, EP AF Fragkos-Livanios, L. Balatsos, N. A. A. Xiao, Z. Veenstra, T. D. Panayotou, G. Rogakou, E. P. TI SoTRIs: a novel fractionation procedure for cellular proteins that participate in functional complexes SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Fragkos-Livanios, L.; Panayotou, G.; Rogakou, E. P.] BSRC Al Fleming, Inst Mol Oncol, Vari, Greece. [Balatsos, N. A. A.] Univ Thessaly, Dept Biochem & Biotechnol, Larisa, Greece. [Xiao, Z.; Veenstra, T. D.] NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 205 EP 205 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300659 ER PT J AU Cano, VSP Medrano, FJ Park, MH Valentini, SR AF Pereiro Cano, V. Soares Medrano, F. J. Park, M. Hee Valentini, S. R. TI Structural analysis of Lia1 from S-cerevisiae: evidence for conformational changes induced by iron displacement from its active site SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE SP Federat Biochem Soc, Int Union Biochem & Mol Biol C1 [Pereiro Cano, V. Soares; Valentini, S. R.] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, Sao Paulo, Brazil. [Medrano, F. J.] Univ Estadual Campinas, Inst Biol, Dept Genet & Evolut, Sao Paulo, Brazil. [Park, M. Hee] Natl Inst Dental & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RI Valentini, Sandro/C-4353-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 230 EP 230 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300761 ER PT J AU Van Der Watt, PJ Maske, CP Hendricks, DT Parker, MI Denny, L Govender, D Birrer, MJ Leaner, VD AF Van Der Watt, P. J. Maske, C. P. Hendricks, D. T. Parker, M. I. Denny, L. Govender, D. Birrer, M. J. Leaner, V. D. TI A critical role for the karyopherin proteins, Crm1 and Kpn beta 1, in cancer cell survival and proliferation SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Van Der Watt, P. J.; Hendricks, D. T.; Leaner, V. D.] Univ Cape Town, Fac Hlth Sci, Div Med Biochem, ZA-7925 Cape Town, South Africa. [Maske, C. P.; Govender, D.] Univ Cape Town, Fac Hlth Sci, Div Anat Pathol, ZA-7925 Cape Town, South Africa. [Parker, M. I.] Univ Cape Town, Fac Hlth Sci, Int Ctr Genet Engn & Biotechnol, ZA-7925 Cape Town, South Africa. [Denny, L.] Univ Cape Town, Fac Hlth Sci, Dept Obstet & Gynaecol, ZA-7925 Cape Town, South Africa. [Birrer, M. J.] NCI, NIH, Dept Cell & Canc Biol, Bethesda, MD 20892 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 JUN PY 2008 VL 275 SU 1 BP 468 EP 468 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633301671 ER PT J AU Howards, PP Cooney, MA AF Howards, Penelope P. Cooney, Maureen A. TI Disentangling causal paths between obesity and in vitro fertilization outcomes: an intractable problem? SO FERTILITY AND STERILITY LA English DT Editorial Material ID OOCYTE DONATION AB Research questions should be appropriate for the available data. Disentangling causal paths between obesity and in vitro fertilization outcomes may be an intractable problem, but other research questions of clinical importance can be addressed through appropriate study designs and analytic methods. (Fertil Steril (R) 2008;89:1604-5. (c) 2008 by American Society for Reproductive Medicine.). C1 [Howards, Penelope P.; Cooney, Maureen A.] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Howards, PP (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03C MSC 7510, Bethesda, MD 20892 USA. EM howardsp@mail.nih.gov FU Intramural NIH HHS NR 4 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2008 VL 89 IS 6 BP 1604 EP 1605 DI 10.1016/j.fertnstert.2007.03.093 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 315PT UT WOS:000256892600003 PM 17588569 ER PT J AU Levens, ED Skarulis, MC AF Levens, Eric D. Skarulis, Monica C. TI Assessing the role of endometrial alteration among obese patients undergoing assisted reproduction SO FERTILITY AND STERILITY LA English DT Editorial Material ID IN-VITRO FERTILIZATION; C-REACTIVE PROTEIN; BODY-MASS INDEX; SPONTANEOUS-ABORTION; INSULIN-RESISTANCE; RECURRENT MISCARRIAGE; OOCYTE DONATION; ADIPOSE-TISSUE; POTENTIAL ROLE; RISK AB Obesity seems to exert a small but important extraovarian effect that may influence cycle outcome during assisted reproduction. Future investigation should focus on elucidating whether the endometriurn is truly responsible for this deficit, and if it is, determining the mechanisms involved. (Fertil Steril (R) 2008;89:1606-8. (c) 2008 by American Society for Reproductive Medicine.). C1 [Levens, Eric D.] NICHHD, Reprod Biol & Med Branch, CRC, Bethesda, MD 20892 USA. [Skarulis, Monica C.] NIDDK, Clin Endocrinol Branch, Natl Inst Hlth, Bethesda, MD USA. [Levens, Eric D.] Walter Reed Army Med Ctr, Natl Inst Hlth, Natl Naval Med Ctr, Washington, DC 20307 USA. [Levens, Eric D.] Univ Hlth Sci, Uniformed Serv, Washington, DC USA. RP Levens, ED (reprint author), NICHHD, Reprod Biol & Med Branch, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM levense@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 24 TC 12 Z9 15 U1 1 U2 2 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 JUN PY 2008 VL 89 IS 6 BP 1606 EP 1608 DI 10.1016/j.fertnstert.2007.03.079 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 315PT UT WOS:000256892600004 PM 17531230 ER PT J AU Stegmann, BJ Sinaii, N Liu, S Segars, J Merino, M Nieman, LK Stratton, P AF Stegmann, Barbara J. Sinaii, Ninet Liu, Shannon Segars, James Merino, Maria Nieman, Lynnette K. Stratton, Pamela TI Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Society-for-Reproductive-Medicine/51st Annual Meeting of the Canadian-Fertility-and-Andrology-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc DE endometriosis; lesion characteristics; lesion color; prediction of endometriosis; laparoscopy; surgical diagnosis ID VISUAL FINDINGS; LAPAROSCOPY; DIAGNOSIS; ACCURACY AB Objective: To correlate histology with endometriosis characteristics. Design: Secondary data analysis. Setting: Government research hospital. Patient(s): One hundred thirty-three women with chronic pelvic pain and endometriosis who underwent laparoscopic surgery between 1999 and 2004. Intervention(s): Laparoscopic excision of lesions, including recording of lesion characteristics and surgical impression of the lesions. Main Outcome Measure(S): All biopsies were sent for histological examination for endometriosis, and surgical and histological findings were compared. Result(s): Three hundred fifty-seven of 544 lesions believed to be endometriosis by the surgeon had positive histology. Mixed-color lesions most commonly contained endometriosis (76%), with the percentage of positive lesions being similar between single-color groups. Among subtle (red or white) lesions, 58% (164/283) were positive for endometriosis. Thirty women had only red or white lesions, and 18 (60%) had at least one lesion positive for endometriosis. Lesions were most commonly located in the cul-de-sac (64%), utero-sacral ligaments (68%), and ovarian fossa (70%). Conclusion(s): Wide, deep, mixed-color lesions in the cul-de-sac, the ovarian fossa, or the utero-sacral ligaments had the highest frequency of endometriosis. More than half of subtle lesions had endometriosis. These results should be considered when diagnosing endometriosis. (Fertil Steril (R) 2008;89:1632 -6. (c) 2008 by American Society for Reproductive Medicine.). C1 [Stegmann, Barbara J.; Liu, Shannon; Segars, James; Nieman, Lynnette K.; Stratton, Pamela] NICHHD, Reprod Biol & Med Branch, Natl Inst Hlth, Clin Res Ctr, Bethesda, MD 20892 USA. [Sinaii, Ninet] Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD USA. [Segars, James] NCI, Surg Pathol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NICHHD, Reprod Biol & Med Branch, Natl Inst Hlth, Clin Res Ctr, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM strattop@mail.nih.gov FU Intramural NIH HHS [Z01 HD008728-07] NR 17 TC 23 Z9 24 U1 0 U2 1 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 JUN PY 2008 VL 89 IS 6 BP 1632 EP 1636 DI 10.1016/j.fertnstert.2007.05.042 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 315PT UT WOS:000256892600010 PM 17662280 ER PT J AU Whitcomb, BW Schisterman, EF Klebanoff, MA Baumgarten, M Luo, X Chegini, N AF Whitcomb, Brian W. Schisterman, Enrique F. Klebanoff, Mark A. Baumgarten, Mona Luo, Xiaoping Chegini, Nasser TI Circulating levels of cytokines during pregnancy: thrombopoietin is elevated in miscarriage SO FERTILITY AND STERILITY LA English DT Article DE cytokines; epidemiology; hematopoiesis; miscarriage; placentation ID NECROSIS-FACTOR-ALPHA; T-HELPER CYTOKINES; SPONTANEOUS-ABORTION; RECURRENT MISCARRIAGE; WOMEN; CELLS; PREECLAMPSIA; EXPRESSION; RISK; REPRODUCTION AB Objective: To evaluate the hypothesis that cytokine levels are associated with miscarriage risk using serum samples collected before report of miscarriage. Design: A nested case-control study. Setting: Biospecimens from the multisite Collaborative Perinatal Project, University of Florida, laboratory assessment of interleukin (IL)-1 receptor antagonist, IL-1 beta, IL-4, IL-6, Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, thrombopoietin (TPO), and granulocyte colony-stimulating factor (G-CSF). Patient(s): Cases of miscarriage (n = 439) were matched to control,, (n = 373) by gestational age at sample collection. Intervention(s): None. Main Outcome Measure(s): Miscarriage. Result(s): Increased risk of miscarriage was associated with elevated TPO (adjusted odds ratio [OR] 1.16, 95% confidence interval [CI] 1.00-1.36) and decreased G-CSF (adjusted OR 0.78, 95% Cl 0.64-0.95). When analysis was restricted to samples collected more than 35 days before miscarriage, the effect of G-CSF was not observed (adjusted OR 0.96, 95% Cl 0.72-1.28), whereas increased risk related to higher TPO remained. Conclusion(s): Circulating levels of TPO may be associated with increased risk of miscarriage. C1 [Whitcomb, Brian W.; Schisterman, Enrique F.; Klebanoff, Mark A.] NICHHD, Epidemiol Branch, DESPR, NIH, Rockville, MD 20852 USA. [Baumgarten, Mona] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD USA. [Luo, Xiaoping; Chegini, Nasser] Univ Florida, Dept Obstet & Gynecol, Gainesville, FL USA. RP Schisterman, EF (reprint author), NICHHD, Epidemiol Branch, DESPR, NIH, 6100 Executive Blvd,Rm 7B03, Rockville, MD 20852 USA. EM SchisteE@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008762-05] NR 47 TC 10 Z9 12 U1 0 U2 6 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 JUN PY 2008 VL 89 IS 6 BP 1795 EP 1802 DI 10.1016/j.fertnstert.2007.05.046 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 315PT UT WOS:000256892600034 PM 17706203 ER PT J AU Abbott, D Doering, CR Caves, CM Lidar, DM Brandt, HE Hamilton, AR Ferry, DK Gea-Banacloche, J Bezrukov, SM Kish, LB AF Abbott, D. Doering, C. R. Caves, C. M. Lidar, D. M. Brandt, H. E. Hamilton, A. R. Ferry, D. K. Gea-Banacloche, J. Bezrukov, S. M. Kish, L. B. TI Dreams versus reality: Plenary debate session on quantum computing SO FLUCTUATION AND NOISE LETTERS LA English DT Editorial Material C1 [Abbott, D.] Univ Adelaide, Ctr Biomed Engn, Adelaide, SA 5005, Australia. [Abbott, D.] Univ Adelaide, Dept Elect & Elect Engn, Adelaide, SA 5005, Australia. [Doering, C. R.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. [Doering, C. R.] Univ Michigan, Michigan Ctr Theoret Phys, Ann Arbor, MI 48109 USA. [Caves, C. M.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. [Lidar, D. M.] Univ Toronto, Dept Chem, Chem Phys Theory Grp, Toronto, ON M5S 3H6, Canada. [Lidar, D. M.] Univ Toronto, Ctr Quantum Informat & Quantum Control, Toronto, ON M5S 3H6, Canada. [Brandt, H. E.] USA, Res Lab, Adelphi, MD 20783 USA. [Hamilton, A. R.] Univ New S Wales, Sch Phys, Ctr Quantum Comp Technol, Sydney, NSW 2052, Australia. [Ferry, D. K.] Arizona State Univ, Dept Elect Engn, Tempe, AZ 85287 USA. [Gea-Banacloche, J.] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA. [Bezrukov, S. M.] NICHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. [Kish, L. B.] Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. RP Abbott, D (reprint author), Univ Adelaide, Ctr Biomed Engn, Adelaide, SA 5005, Australia. RI Lidar, Daniel/A-5871-2008; Abbott, Derek/E-8352-2011; Hamilton, Alex/A-5639-2011; Caves, Carlton/K-8167-2014 OI Lidar, Daniel/0000-0002-1671-1515; Abbott, Derek/0000-0002-0945-2674; Hamilton, Alex/0000-0001-7484-3738; Caves, Carlton/0000-0001-8876-1186 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0219-4775 J9 FLUCT NOISE LETT JI Fluct. Noise Lett. PD JUN PY 2008 VL 8 IS 2 BP C27 EP C51 DI 10.1142/S0219477508004337 PG 25 WC Mathematics, Interdisciplinary Applications; Physics, Applied SC Mathematics; Physics GA 323KU UT WOS:000257445800001 ER PT J AU Baig-Ansari, N Badruddin, SH Karmaliani, R Harris, H Jehan, I Pasha, O Moss, N McClure, EM Goldenberg, RL AF Baig-Ansari, Naila Badruddin, Salma Halai Karmaliani, Rozina Harris, Hillary Jehan, Imtiaz Pasha, Omrana Moss, Nancy McClure, Elizabeth M. Goldenberg, Robert L. TI Anemia prevalence and risk factors in pregnant women in an urban area of Pakistan SO FOOD AND NUTRITION BULLETIN LA English DT Article DE anemia; developing countries; pregnancy ID DEVELOPING-COUNTRIES; IRON; DEFICIENCY; NUTRITION; IMPACT AB Background. Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight. Objective. To determine the prevalence of anemia and the dietary and socioeconomic factors associated with anemia in pregnant women living in an urban community setting in Hyderabad, Pakistan. Methods. This was a prospective, observational study of 1,369 pregnant women enrolled at 20 to 26 weeks of gestation andfollowed to 6 weeks postpartum. A blood sample was obtained at enrollment to determine hemoglobin levels. Information on nutritional knowledge, attitudes, and practice and dietary history regarding usual food intake before and duringpregnancy were obtained by trained interviewers within I week of enrollment. Results. The prevalence of anemia (dej'ined by the World Health Organization as hemoglobin < 11.0 g/dL) in these subjects was 90.5%; of these, 75.0% had mild anemia (hemoglobinfrom 9.0 to 10.9g/dL) and 14.8% had moderate anemia (hemoglobinftom 7.0 to 8.9g/dL). Only 0.7% were severely anemic (hemoglobin < 7.0 g/dL). Nonanemic women were significantly taller, weighed more, and had a higher body mass index. Multivariate analysis after adjustmentfor education, pregnancy history, iron supplementation, and height showed that drinking more than three cups of tea per day before pregnancy (adjusted prevalence odds ratio [aPOR], 3.2; 95% confidence interval [CI], 1.3 to 8.0), consumption of clay or dirt duringpregnancy (aPOR, 3.7; 95% CI, 1.1 to 12.3), and never consuming eggs or consuming eggs less than twice a week during pregnancy (aPOR, 1. 7; 95% CI, 1.1 to 2.5) were significantly associated with anemia. Consumption of red meat less than twice a week prior to pregnancy was marginally associated with anemia WOR, 1.2; 95% CI, 0.8 to 1.8) but was significantly associated with lower mean hemoglobin concentrations (9.9 vs. 10.0 g/dL, p :=.05) during the study period. A subanalysis excluding women with mild anemia found similar associations to those of the main model, albeit even stronger. Conclusions. A high percentage of women at 20 to 26 weeks ofpregnancy had mild to moderate anemia. Pica, tea consumption, and low intake of eggs and red meat were associated with anemia. Women of childbearing age should be provided nutritional education regarding food sources of iron, especially prior to becoming pregnant, and taught howfood choices can either enhance or interfere with iron absorption. C1 [Baig-Ansari, Naila] Univ Calif Davis, Davis, CA 95616 USA. [Badruddin, Salma Halai; Karmaliani, Rozina; Jehan, Imtiaz; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan. [Harris, Hillary; McClure, Elizabeth M.] Res Triangle Inst, Durham, NC USA. [Moss, Nancy] NICHHD, Bethesda, MD 20892 USA. [Goldenberg, Robert L.] Drexel Univ, Philadelphia, PA 19104 USA. EM nbansari@ucdavis.edu OI Baig-Ansari, Naila/0000-0003-0335-056X FU NICHD NIH HHS [U01 HD040607, HD40636-06, HD40607-04, U01 HD040636] NR 28 TC 31 Z9 38 U1 2 U2 5 PU INT NUTRITION FOUNDATION PI BOSTON PA 150 HARRISON AVE, BOSTON, MA 02111 USA SN 0379-5721 J9 FOOD NUTR BULL JI Food Nutr. Bull. PD JUN PY 2008 VL 29 IS 2 BP 132 EP 139 PG 8 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 320RQ UT WOS:000257253100007 PM 18693477 ER PT J AU Molloy, AM Kirke, PN Brody, LC Scott, JM Mills, JL AF Molloy, Anne M. Kirke, Peadar N. Brody, Lawrence C. Scott, John M. Mills, James L. TI Effects of folate and vitamin B-12 deficiencies during pregnancy on fetal, infant, an child development SO FOOD AND NUTRITION BULLETIN LA English DT Review DE child; deficiency; development; fetal; folate; infant; pregnancy; vitamin B-12 ID NEURAL-TUBE DEFECTS; FOLIC-ACID SUPPLEMENTATION; SEVERE ABRUPTIO PLACENTAE; LONG-TERM MORTALITY; BREAST-FED INFANTS; HUMAN-MILK FOLATE; HOMOCYSTEINE LEVELS; AMNIOTIC-FLUID; METHYLMALONIC ACID; BIRTH-WEIGHT AB The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects(NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B-12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B-12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B-12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B-12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B-12 status have not been sufficiently researched. C1 [Molloy, Anne M.] Trinity Coll Dublin, Sch Med, Dublin 2, Ireland. [Kirke, Peadar N.] Hlth Res Board, Dublin, Ireland. [Brody, Lawrence C.] NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Scott, John M.] Trinity Coll Dublin, Sch Biochem, Dublin 2, Ireland. [Mills, James L.] NICHHD, Epidemiol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Molloy, AM (reprint author), Trinity Coll Dublin, Sch Biochem & Immunol, Dublin 2, Ireland. EM amolloy@tcd.ie FU Intramural NIH HHS NR 146 TC 68 Z9 73 U1 5 U2 33 PU INT NUTRITION FOUNDATION PI BOSTON PA 150 HARRISON AVE, BOSTON, MA 02111 USA SN 0379-5721 J9 FOOD NUTR BULL JI Food Nutr. Bull. PD JUN PY 2008 VL 29 IS 2 SU S BP S101 EP S111 PG 11 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 323EC UT WOS:000257425800013 PM 18709885 ER PT J AU Ruden, DM Jamison, DC Zeeberg, BR Garfinkel, MD Weinstein, JN Rasouli, P Lu, XY AF Ruden, Douglas M. Jamison, D. Curtis Zeeberg, Barry R. Garfinkel, Mark D. Weinstein, John N. Rasouli, Parsa Lu, Xiangyi TI The EDGE hypothesis: Epigenetically directed genetic errors in repeat-containing proteins (RCPs) involved in evolution, neuroendocrine signaling, and cancer SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE repeat-containing proteins (RCPs); neuroendocrine signaling; evolution; cancer; epigenetics; trans-generational epigenetics; endocrine disruptors; Hsp90; trinucleotide repeats ID FRAGILE-X-SYNDROME; DNA METHYLATION; MORPHOLOGICAL EVOLUTION; ACQUIRED CHARACTERS; INHERITANCE; HSP90; DOMESTICATION; CHROMATIN; SYSTEM; GENOME AB Trans-generational epigenetic phenomena, such as contamination with endocrine-disrupting chemicals (EDCs) that decrease fertility and the global methylation status of DNA in the offspring, are of great concern because they may affect health, particularly the health of children. However, of even greater concern is the possibility that trans-generational changes in the methylation status of the DNA might lead to permanent changes in the DNA sequence itself. By contaminating the environment with EDCs, mankind might be permanently affecting the health of future generations. In this section, we present evidence from our laboratory and others that trans-generational epigenetic changes in DNA might lead to mutations directed to genes encoding amino acid repeat-containing proteins (RCPs) that are important for adaptive evolution or cancer progression. Such epigenetic changes can be induced "naturally" by hormones or "unnaturally" by EDCs or environmental stress. To illustrate the phenomenon, we present new bioinformatic evidence that the only RCP ontological categories conserved from Drosophila to humans are "regulation of splicing," "regulation of transcription," and "regulation of synaptogenesis," which are classes of genes likely to be important for evolutionary processes. Based on that and other evidence, we propose a model for evolution that we call the EDGE (Epigenetically Directed Genetic Errors) hypothesis for the mechanism by which mutations are targeted at epigenetically modified "contingency genes" encoding RCPs. In the model, "epigenetic assimilation" of metastable epialleles of RCPs over many generations can lead to mutations directed to those genes, thereby permanently stabilizing the adaptive phenotype. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ruden, Douglas M.; Rasouli, Parsa; Lu, Xiangyi] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48201 USA. [Jamison, D. Curtis] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA 20110 USA. [Zeeberg, Barry R.; Weinstein, John N.] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Garfinkel, Mark D.] Univ Alabama, Dept Environm Hlth Sci, Birmingham, AL 35294 USA. RP Ruden, DM (reprint author), Wayne State Univ, Inst Environm Hlth Sci, Room 4000,2727 2nd Ave, Detroit, MI 48201 USA. EM douglasr@wayne.edu; cjamison@zoomtown.com FU Intramural NIH HHS; NCI NIH HHS [R01 CA105349-01, R01 CA105349]; NIDDK NIH HHS [R01 DK 07173]; NIEHS NIH HHS [R01 ES012933-01, R01 ES012933, P30 ES06639] NR 70 TC 14 Z9 14 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JUN PY 2008 VL 29 IS 3 BP 428 EP 444 DI 10.1016/j.yfrne.2007.12.004 PG 17 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 306KV UT WOS:000256247900008 PM 18295320 ER PT J AU Feld, JJ Hussain, N Wright, EC Kleiner, DE Hoofnagle, JH Ahlawat, S Anderson, V Hilligoss, D Gallin, JI Liang, TJ Malech, HL Holland, SM Heller, T AF Feld, Jordan J. Hussain, Nadeem Wright, Elizabeth C. Kleiner, David E. Hoofnagle, Jay H. Ahlawat, Sushil Anderson, Victoria Hilligoss, Dianne Gallin, John I. Liang, T. Jake Malech, Harry L. Holland, Steven M. Heller, Theo TI Hepatic involvement and portal hypertension predict mortality in chronic granulomatous disease SO GASTROENTEROLOGY LA English DT Article ID NODULAR REGENERATIVE HYPERPLASIA; POLYCYSTIC KIDNEY-DISEASE; HYPERDYNAMIC CIRCULATION; BACTERIAL TRANSLOCATION; ESOPHAGEAL-VARICES; ESCHERICHIA-COLI; INTERFERON-GAMMA; CIRRHOSIS; LIVER; INFECTIONS AB Background & Aims: Chronic granulomatous disease (CGD) is a rare genetic disorder, predisposing affected individuals to recurrent infectious complications and shortened survival. Liver involvement in CGD includes vascular abnormalities, which may lead to noncirrhotic portal hypertension. Methods: To evaluate the impact of noncirrhotic portal hypertension on survival in CGD, all records from 194 patients followed up at the National Institutes of Health with CGD were reviewed. Cox proportional hazards regression was used to determine factors associated with mortality. Results: Twenty-four patients died, all from infectious complications. By Cox regression, factors associated with mortality were as follows: (1) decreases in platelet count (>9000/mu L/y; hazard ratio, 4.7; P=.007), (2) alkaline phosphatase level increases (>0.25/y; hazard ratio, 4.5; P=.01) and (3) history of liver abscess (hazard ratio, 3.1; P=.03). By regression analysis, decreasing platelet count was associated with increasing portal vein diameter, splenomegaly, increased serum immunoglobulin G level, and increasing number of alanine aminotransferase increases; greater number of alkaline phosphatase level increases and abscess were both associated with increasing age and number of infections. Prospective evaluation revealed increased hepatic-venous pressure gradients in 2 patients with progressive thrombocytopenia, suggestive of portal hypertension. Conclusions: These data suggest mortality in patients with CGD is associated with the development of noncirrhotic portal hypertension, likely owing to injury to the microvasculature of the liver from repeated systemic and hepatic infections. The slope of decline in platelet count may be a useful measure of progression of portal hypertension over time. Furthermore, the data illustrate the potential independent effect of portal hypertension on clinical outcome outside the setting of cirrhosis. C1 [Heller, Theo] NIDDK, Liver Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Hussain, Nadeem; Ahlawat, Sushil] NIDDK, Digest Dis Branch, Bethesda, MD USA. [Wright, Elizabeth C.] NIDDK, Off Director, Bethesda, MD USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Anderson, Victoria; Hilligoss, Dianne; Gallin, John I.; Malech, Harry L.; Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA. RP Heller, T (reprint author), NIDDK, Liver Dis Branch, Natl Inst Hlth, Bldg 10,Room 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM Theller@nih.gov OI Malech, Harry/0000-0001-5874-5775; Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS [Z01 DK075008-02] NR 41 TC 29 Z9 29 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2008 VL 134 IS 7 BP 1917 EP 1926 DI 10.1053/j.gastro.2008.02.081 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312QR UT WOS:000256686400017 PM 18439425 ER PT J AU Sukhthankar, M Yamaguchi, K Lee, SH Mcentee, MF Eling, TE Hara, Y Baek, SJ AF Sukhthankar, Mugdha Yamaguchi, Kiyoshi Lee, Seong-Ho Mcentee, Michael F. Eling, Thomas E. Hara, Yukihiko Baek, Seung Joon TI A green tea component suppresses posttranslational expression of basic fibroblast growth factor in colorectal cancer SO GASTROENTEROLOGY LA English DT Article ID COLON-CANCER; (-)-EPICATECHIN GALLATE; UBIQUITIN-BINDING; BLACK TEA; IN-VIVO; CELLS; INHIBITION; APOPTOSIS; PROTEIN; EPIGALLOCATECHIN-3-GALLATE AB Background & Aims: Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis. However, the exact molecular mechanism by which EGCG suppresses bFGF expression is not known. Our objective was to elucidate the molecular mechanisms by which EGCG inhibits bFGF expression in colorectal cancer. Methods: We examined posttranslational regulation of bFGF by EGCG in human colorectal. cancer cells. We also examined bFGF in intestinal tumor formation of APC(Min)/(+) mice with and without catechin treatment. Results: The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein. Furthermore, EGCG suppressed tumor formation in APC(Min)/(+) mice, compared with vehicle-treated mice, in association with reduced bFGF expression. Conclusions: The ubiquitin-proteasome degradation pathway contributes significantly to down-regulation of bFGF expression by EGCG. Cat echin compounds have fewer adverse effects than chemotherapeutic agents and hence can be used as proof-of-concept in cancer therapeutics to suppress growth and metastasis by targeting proteins such as bFGF. C1 [Sukhthankar, Mugdha; Yamaguchi, Kiyoshi; Lee, Seong-Ho; Mcentee, Michael F.; Baek, Seung Joon] Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, Knoxville, TN 37996 USA. [Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Hara, Yukihiko] Mitsui Norin Co Ltd, Food Res Lab, Fujieda, Shizuoka, Japan. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu OI Baek, Seung/0000-0001-7866-7778; McEntee, Michael/0000-0002-1616-3715 FU NCI NIH HHS [R21 CA109423-01A1, R21 CA109423-02, R21 CA109423, R21CA109423]; NCRR NIH HHS [K26 RR016645, K26RR016645] NR 32 TC 38 Z9 41 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2008 VL 134 IS 7 BP 1972 EP 1980 DI 10.1053/j.gastro.2008.02.095 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312QR UT WOS:000256686400022 PM 18549879 ER PT J AU Shah, YM Ito, S Morimura, K Chen, C Yim, SH Haase, VH Gonzalez, FJ AF Shah, Yatrik M. Ito, Shinji Morimura, Keiichirou Chen, Chi Yim, Sun-Hee Haase, Volker H. Gonzalez, Frank J. TI Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade SO GASTROENTEROLOGY LA English DT Article ID MIGRATION-INHIBITORY FACTOR; PAS DOMAIN PROTEIN-1; FACTOR-I; FACTOR 1-ALPHA; BOWEL-DISEASE; TRANSCRIPTIONAL ACTIVITY; ENDOTHELIAL-CELLS; MICE LACKING; HIF-ALPHA; EXPRESSION AB Backgground & Aims: Colon epithelial. cells are critical for barrier function and contain a highly developed immune response. A previous study has shown hypoxia-inducible factor (HIF) as a critical regulator of barrier protection during colon epithelial injury. However, the role of HIF signaling in colon mucosal immunity is not known. Methods: With the use of cre/loxP technology, intestinal-specific disruption of von Hippel-Lindau tumor suppressor protein (Vhl), hypoxia-inducible factor (Hif)-1 alpha, and aryl hydrocarbon nuclear translocator (Arnt) was generated. Colon inflammation was induced using a dextran sulfate sodium (DSS)-induced colitis model, and the mice were analyzed by histologic analysis, Western blot analysis, and quantitative polymerase chain reaction. Results: In mice, colonic epithelium disruption of Vhl resulted in constitutive expression of HIF, which initiated an increase in inflammatory infiltrates and edema in the colon. These effects were ameliorated in mice by disruption of both Vh1 and Arnt/Hif1 beta (which inactivates HIF). In a DSS-induced colitis model, increased HIF expression correlated with more severe clinical symptoms and an increase in histologic damage, while disruption of both Vhl and Arnt in the colon epithelium inhibited these effects. Furthermore, colons with constitutive activation of HIF displayed increased expression of proinflammatory mediators that were synergistically potentiated following DSS administration and reduced by inhibition of the proinflammatory and direct HIF target gene macrophage migration inhibitory factor. Conclusions: The present study shows that a chronic increase in HIF signaling in the colon epithelial cells initiates a hyperinflammatory reaction that may have important implications in developing therapeutic strategies for inflammatory bowel disease. C1 [Shah, Yatrik M.; Ito, Shinji; Morimura, Keiichirou; Chen, Chi; Yim, Sun-Hee; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Haase, Volker H.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Natl Inst Hlth, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Haase, Volker Hans/A-6758-2013 OI Haase, Volker Hans/0000-0002-7051-8994 FU Intramural NIH HHS [Z01 BC005561-20]; NCI NIH HHS [R01 CA100787] NR 53 TC 78 Z9 83 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2008 VL 134 IS 7 BP 2036 EP 2048 DI 10.1053/j.gastro.2008.03.009 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312QR UT WOS:000256686400028 PM 18439915 ER PT J AU Schoen, RE Mutch, M Rall, C Dry, SM Seligson, D Umar, A Pinsky, P AF Schoen, Robert E. Mutch, Matthew Rall, Christopher Dry, Sarah M. Seligson, David Umar, Asad Pinsky, Paul TI The natural history of aberrant crypt foci SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CANCER SCREENING TRIAL; COLON; IDENTIFICATION; COLONOSCOPY AB Background: Aberrant crypt foci (ACF) are the putative precursors to colorectal adenomas and may be useful as biomarkers. Knowledge of their natural history is essential to understanding their potential utility. Objective: Our purpose was to examine ACF detection 1 year after initial observation. Design: We conducted a multicenter study of ACF by using a standardized protocol. ACF in the rectum were assessed and subjects returned 1 year later to evaluate the natural history of the lesions. Setting: Ancillary study to the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Results: Of 78 subjects enrolled, 64 (82%) returned for a repeat examination 1 year later. The mean age was 71 years, 70% were male, and 54% had a history of adenomatous polyps. At the initial examination, 66% of subjects had at least 1 ACF detected in the rectum, with a mean of 2.1 +/- 2.3 per person. One year later, 60% of these subjects had at least 1 of the original ACF reidentified, but only 43% of all ACF were reidentified. A total of 56% of subjects had new ACF identified. Limitations: These results are generated from the pilot phase. Improvements or change in technique over time could have influenced the results. Conclusions: A total of 60% of subjects who had ACF continued to have at least one ACF 1 year later, but less than half the specific ACF could be reidentified, and more than 50% of subjects had new ACE These results imply a considerable dynamic to ACF detection over a 1-year period of observation. C1 [Schoen, Robert E.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Mutch, Matthew] Washington Univ, St Louis, MO USA. [Rall, Christopher] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Dry, Sarah M.; Seligson, David] Univ Calif Los Angeles, Los Angeles, CA USA. [Umar, Asad; Pinsky, Paul] NCI, Bethesda, MD 20892 USA. RP Schoen, RE (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Mezzanine Level,C Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 13 TC 20 Z9 20 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 JUN PY 2008 VL 67 IS 7 BP 1097 EP 1102 DI 10.1016/j.gie.2007.08.048 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 310GE UT WOS:000256516100017 PM 18178205 ER PT J AU Nirenberg, M AF Nirenberg, M. TI Introduction to AAV Vector special issue SO GENE THERAPY LA English DT Editorial Material C1 NHLBI, Bethesda, MD 20892 USA. RP Nirenberg, M (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM nirenbem@nhlbi.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 2008 VL 15 IS 11 BP 807 EP 807 DI 10.1038/gt.2008.62 PG 1 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 303VG UT WOS:000256068400001 PM 18490934 ER PT J AU Smith, RH AF Smith, R. H. TI Adeno-associated virus integration: virus versus vector SO GENE THERAPY LA English DT Review DE AAV; adeno-associated virus; integration ID SITE-SPECIFIC INTEGRATION; CELLULAR DNA; REP PROTEINS; TARGETED INTEGRATION; LIVER TRANSDUCTION; DETROIT-6 CELLS; MOUSE-LIVER; GENOME; AAV; SEQUENCES AB Although a large percentage of the world population is seropositive for exposure to various strains of adeno-associated virus ( AAV), a human parvovirus, AAV has never been identified as an etiologic agent of human disease. Most likely contributing to the pronounced lack of pathogenicity is the fact that AAV is a naturally 'defective' virus that requires a helper virus for productive replication of its genome. Another unusual aspect of wild-type AAV biology is the ability of the virus to establish latent infection by preferential integration of its genome into a specific locus of human chromosome 19. Site-specific integration was a major impetus for the development of recombinant AAV vectors, which typically lack all AAV coding sequences. It was soon realized, however, that expression of at least one species of the virally encoded initiator proteins, Rep78 or Rep68, is necessary for targeted integration of AAV-derived DNA constructs to occur. This article will present a chronological outline of studies characterizing site-specific integration of wild-type AAV sequences and the quasi-random target site selection observed with recombinant AAV vectors. C1 NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. RP Smith, RH (reprint author), NHLBI, Lab Biochem Genet, Bldg 10,Room 7N264, Bethesda, MD 20892 USA. EM smithr@nhlbi.nih.gov FU Intramural NIH HHS NR 31 TC 54 Z9 56 U1 1 U2 5 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 JUN PY 2008 VL 15 IS 11 BP 817 EP 822 DI 10.1038/gt.2008.55 PG 6 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 303VG UT WOS:000256068400003 PM 18401436 ER PT J AU Cecchini, S Negrete, A Kotin, RM AF Cecchini, S. Negrete, A. Kotin, R. M. TI Toward exascale production of recombinant adeno-associated virus for gene transfer applications SO GENE THERAPY LA English DT Review DE rAAV; bioprocess; baculovirus; large scale; Sf9 ID BACULOVIRUS EXPRESSION SYSTEM; ION-EXCHANGE CHROMATOGRAPHY; INSECT-CELL CULTURES; MEDIATED MICRODYSTROPHIN EXPRESSION; ROTAVIRUS SUBUNIT VACCINE; LARGE-SCALE PRODUCTION; VIRAL VECTORS; PROTEIN-PRODUCTION; DYSTROPHIC MUSCLE; TYPE-2 VECTORS AB To gain acceptance as a medical treatment, adeno-associated virus (AAV) vectors require a scalable and economical production method. Recent developments indicate that recombinant AAV (rAAV) production in insect cells is compatible with current good manufacturing practice production on an industrial scale. This platform can fully support development of rAAV therapeutics from tissue culture to small animal models, to large animal models, to toxicology studies, to Phase I clinical trials and beyond. Efforts to characterize, optimize and develop insect cell-based rAAV production have culminated in successful bioreactor-scale production of rAAV, with total yields potentially capable of approaching the 'exa-(10(18)) scale.' These advances in large-scale AAV production will allow us to address specific catastrophic, intractable human diseases such as Duchenne muscular dystrophy, for which large amounts of recombinant vector are essential for successful outcome. C1 [Cecchini, S.; Negrete, A.; Kotin, R. M.] NHLBI, NIH, Lab Biochem Genet, Bethesda, MD 20817 USA. RP Kotin, RM (reprint author), NHLBI, NIH, Lab Biochem Genet, 10 Ctr Dr,Bldg 10,Room 7D18, Bethesda, MD 20817 USA. EM kotinr@nhlbi.nih.gov RI kotin, robert/B-8954-2008 FU Intramural NIH HHS NR 73 TC 25 Z9 26 U1 0 U2 6 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 JUN PY 2008 VL 15 IS 11 BP 823 EP 830 DI 10.1038/gt.2008.61 PG 8 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 303VG UT WOS:000256068400004 PM 18401433 ER PT J AU Grant, LR Yao, ZJ Hedrich, CM Wang, F Moorthy, A Wilson, K Ranatunga, D Bream, JH AF Grant, L. R. Yao, Z-J Hedrich, C. M. Wang, F. Moorthy, A. Wilson, K. Ranatunga, D. Bream, J. H. TI Stat4-dependent, T-bet-independent regulation of IL-10 in NK cells SO GENES AND IMMUNITY LA English DT Article DE natural killer cells; cytokines; IL-10; Stat4; IL-12 ID IFN-GAMMA PRODUCTION; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; INTERLEUKIN-10 PROMOTER; IMMUNOREGULATORY ROLES; TRANSCRIPTION FACTOR; STIMULATORY FACTOR; GENE-EXPRESSION; TH2 CELLS; P38 AB Interleukin-10 (IL-10) is intensely studied, yet little is known about the mechanisms that control IL-10 expression. We identified striking similarities between IL-10 and interferon-gamma (IFN-gamma) regulation in mouse natural killer (NK) cells. Like IFN-gamma, IL-10 expression is induced by IL-2 and IL-12 and IL-2 + IL-12 stimulation is synergistic. Unlike IFN-gamma, neither IL-18 nor Ly-49D cross-linking induced IL-10 expression however. Additionally, the IL-12 homologs IL-23 and IL-27 also do not regulate NK cell-specific IL-10. We determined that a small population of NK cells accounts for IL-10 production. The induction of IL-10 by IL-2 + IL-12 treatment in NK cells appears to be biphasic, with an initial burst of expression which diminishes by 12 h but spikes again at 18 h. We determined that much like IFN-gamma, Stat4 is largely required for IL-12-induced IL-10. Conversely, we observed normal induction of IL-10 in T-bet-deficient NK cells. We identified a Stat4-binding element in the fourth intron of the ll10 gene, which is completely conserved between mouse and human. This intronic Stat4 motif is within a conserved noncoding sequence, which is also a target for cytokine-induced histone acetylation. These findings highlight tissue-and receptor-specific IL-10 regulatory mechanisms, which may be part of an early feedback loop. C1 [Grant, L. R.; Hedrich, C. M.; Wang, F.; Moorthy, A.; Ranatunga, D.; Bream, J. H.] Johns Hopkins Univ, W Harry Feinstone Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Yao, Z-J; Wilson, K.] NIAMSD, Lymphocyte & Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. RP Bream, JH (reprint author), Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. EM jbream@jhsph.edu FU NIAID NIH HHS [R56 AI070594, R01 AI070594, R01 AI070594-02, AI070594] NR 65 TC 45 Z9 47 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 JUN PY 2008 VL 9 IS 4 BP 316 EP 327 DI 10.1038/gene.2008.20 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 308KJ UT WOS:000256388500006 PM 18401353 ER PT J AU Rhodes, SL Erlich, H Im, KA Wang, J Li, J Bugawan, T Jeffers, L Tong, X Su, X Rosen, HR Yee, LJ Liang, TJ Yang, H AF Rhodes, S. L. Erlich, H. Im, K. A. Wang, J. Li, J. Bugawan, T. Jeffers, L. Tong, X. Su, X. Rosen, H. R. Yee, L. J. Liang, T. J. Yang, H. CA Virahep C Study Grp TI Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection SO GENES AND IMMUNITY LA English DT Article DE human major histocompatability complex; chronic hepatitis C infection; pegylated interferon and ribavirin therapy; African Americans; Caucasian Americans ID CLASS-II ALLELES; AMERICAN PATIENTS; AFRICAN-AMERICAN; PLUS RIBAVIRIN; UNITED-STATES; PEGINTERFERON; GENOTYPE-1; HAPLOTYPES; POPULATIONS; TYPE-1 AB The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; similar to 30%) compared to Caucasian Americans (CA; similar to 50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-alpha-2a and ribavirin. We observed carriage of A*02 (RR = 1.33(1.08-1.64); P = 0.008), B*58 (RR = 1.84(1.24-2.73); P = 0.002) and DPB1* 1701 (RR = 1.57(1.09-2.26); P = 0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted. C1 [Im, K. A.; Yee, L. J.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Erlich, H.; Wang, J.; Li, J.; Bugawan, T.] Roche Mol Syst Inc, Alameda, CA USA. [Rhodes, S. L.; Tong, X.; Yang, H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Im, K. A.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Jeffers, L.] Vet Affairs Med Ctr, Ctr Liver Dis, Dept Med, Miami, FL 33125 USA. [Rosen, H. R.] Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Denver, CO USA. [Yee, L. J.] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Liang, T. J.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Yang, H.] AstraZeneca Pharmaceut LP, Dept Discovery Med & Epidemiol, Wilmington, DE USA. RP Yee, LJ (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, A511 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM YeeL@edc.pitt.edu FU Intramural NIH HHS; NCRR NIH HHS [M01 RR016500, M01 RR000042, M02 RR000079, M01 RR000079, M01 RR00645, M01 RR000645, 1KL2 RR02154-02, M01 RR000046, M01 RR16500, KL2 RR024154]; NIDDK NIH HHS [U01 DK060349, U01 DK60340, U01 DK060345, U01 DK60349, U01 DK60346, U01 DK60344, U01 DK060352, U01 DK60309, U01 DK060344, U01 DK060309, U01 DK60342, U01 DK060341, U01 DK060324, U01 DK060329, U01 DK60341, U01 DK060340, U01 DK60329, U01 DK060341-05, U01 DK60335, U01 DK60327, U01 DK60352, U01 DK060346, U01 DK060335, U01 DK060327, U01 DK60324, U01 DK060342, U01 DK60345] NR 24 TC 18 Z9 19 U1 0 U2 1 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 JUN PY 2008 VL 9 IS 4 BP 328 EP 333 DI 10.1038/gene.2008.21 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 308KJ UT WOS:000256388500007 PM 18418397 ER PT J AU Jones, P Chase, K Martin, A Davern, P Ostrander, EA Lark, KG AF Jones, Paul Chase, Kevin Martin, Alan Davern, Pluis Ostrander, Elaine A. Lark, Karl G. TI Single-nucleotide-polymorphism-based association mapping of dog stereotypes SO GENETICS LA English DT Article ID PORTUGUESE WATER DOGS; DOMESTIC DOG; LINKAGE DISEQUILIBRIUM; MAJOR DETERMINANT; CANIS-FAMILIARIS; BREEDS; DISEASE; SIZE; CHROMOSOME; GENETICS AB Phenotypic stereotypes are traits, often polygenic, that have been stringently selected to conform to specific criteria. In dogs, Canis familiaris, stereotypes result from breed standards set for conformation, performance (behaviors), etc. As a consequence, phenotypic values measured on a few individuals are representative of the breed stereotype. We used DNA samples isolated from 148 (log breeds to associate SNP markers with breed stereotypes. Using size as a trait to test the method, we identified six significant quantitative trait loci (QTL) on live chromosomes that include candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Less well-documented data for behavioral stereotypes tentatively identified loci for herding, pointing, boldness, and trainability. Four significant loci were identified for longevity, a breed characteristic not under direct selection, but inversely correlated with breed size. The strengths and limitations of the approach are discussed as well as its potential to identify loci regulating the within-breed incidence of specific polygenic diseases. C1 [Jones, Paul; Martin, Alan] WALTHAM Ctr Pet Nutr, Melton Mowbray LE14 4RT, Leics, England. [Chase, Kevin; Lark, Karl G.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. [Davern, Pluis] Sundowners Kennels, Gilroy, CA 95020 USA. [Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Lark, KG (reprint author), Univ Utah, Dept Biol, 257 S 1400 E,Room 201, Salt Lake City, UT 84102 USA. EM lark@bioscience.utah.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM063056-06, GM063056, R01 GM063056] NR 54 TC 65 Z9 66 U1 79 U2 115 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 2008 VL 179 IS 2 BP 1033 EP 1044 DI 10.1534/genetics.108.087866 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 315PV UT WOS:000256892800028 PM 18505865 ER PT J AU Varela-Lema, L Taioli, E Ruano-Ravina, A Barros-Dios, JM Anantharaman, D Benhamou, S Boccia, S Bhisey, RA Cadoni, G Capoluongo, E Chen, CJ Foulkes, WD Goloni-Bertollo, EM Hatagima, A Hayes, RB Katoh, T Koifman, S Lazarus, P Manni, JJ Mahimkar, M Morita, S Park, J Park, KK Bertelli, ECP Ribeiro, EMDSF Roy, B Spitz, MR Strange, RC Wei, QY Ragin, CC AF Varela-Lema, Leonor Taioli, Emanuela Ruano-Ravina, Alberto Barros-Dios, Juan M. Anantharaman, Devasena Benhamou, Simone Boccia, Stefania Bhisey, Rajani A. Cadoni, Gabriella Capoluongo, Ettore Chen, Chien-Jen Foulkes, William D. Goloni-Bertollo, Eny Maria Hatagima, Ana Hayes, Richard B. Katoh, Takahiko Koifman, Sergio Lazarus, Phillip Manni, Johannes J. Mahimkar, Manoj Morita, Shunji Park, Jong Park, Kwang-Kyun Pavarino Bertelli, Erika Cristina de Souza Fonseca Ribeiro, Enilze Maria Roy, Bidyut Spitz, Margaret R. Strange, Richard C. Wei, Qingyi Ragin, Camille C. TI Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review SO GENETICS IN MEDICINE LA English DT Review DE GSTM1; CYP1A1; oral and pharyngeal cancers; epidemiology; meta-analysis and pooled analysis ID GLUTATHIONE-S-TRANSFERASE; SQUAMOUS-CELL CARCINOMA; DNA ADDUCT LEVELS; MICROSOMAL EPOXIDE HYDROLASE; DRUG-METABOLIZING-ENZYMES; TOBACCO-RELATED CANCERS; RIO-DE-JANEIRO; NECK-CANCER; GENETIC POLYMORPHISMS; HUMAN-PAPILLOMAVIRUS AB The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4-2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3-3.1; ORm1m2 (or) ([infi]m2m2): 1.3 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. bur findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer. C1 [Taioli, Emanuela; Ragin, Camille C.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA. [Anantharaman, Devasena; Mahimkar, Manoj] Tata Mem Hosp, ACTREC, Canc Res Inst, Bombay 400012, Maharashtra, India. [Benhamou, Simone] NSERM & Evry Univ, Evry, France. [Boccia, Stefania; Cadoni, Gabriella; Capoluongo, Ettore] Catholic Univ, Mol Biol Lab, Inst Hyg Otorhinolaryngol & Biochem, Dept Genet Epidemiol, Rome, Italy. [Boccia, Stefania; Cadoni, Gabriella; Capoluongo, Ettore] Catholic Univ, Mol Biol Lab, Inst Hyg Otorhinolaryngol & Biochem, Mol Biol Unit, Rome, Italy. [Bhisey, Rajani A.] Canc Res Inst, Bombay, Maharashtra, India. [Chen, Chien-Jen] Natl Taiwan Univ, Taipei 10764, Taiwan. [Foulkes, William D.] Montreal Gen Hosp, Quebec City, PQ, Canada. [Goloni-Bertollo, Eny Maria; Pavarino Bertelli, Erika Cristina] Sch Med, Dept Mol Biol, Sao Jose Do Rio Preto, Brazil. [Hatagima, Ana] Inst Oswaldo Cruz, Dept Genet, BR-20001 Rio De Janeiro, Brazil. [Hayes, Richard B.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol Genet, Bethesda, MD 20892 USA. [Katoh, Takahiko] Kumamoto Univ, Dept Publ Hlth, Kumamoto, Japan. [Koifman, Sergio] Natl Sch Publ Hlth, Dept Epidemiol & Quantitat Methods Hlth, Rio de Janeiro, Brazil. [Lazarus, Phillip] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA USA. Penn State Univ, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA USA. [Manni, Johannes J.] Univ Hosp Maastricht, Dept Otorhinolaryngol, Maastricht, Netherlands. [Morita, Shunji] Yao Municipal Hosp, Yao, Japan. [Park, Jong] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Interdisciplinary Oncol, Tampa, FL 33682 USA. [Park, Kwang-Kyun] Yonsei Univ Dent, Dept Oral Biol, Seoul, South Korea. [de Souza Fonseca Ribeiro, Enilze Maria] Univ Fed Parana, Dept Genet, BR-80060000 Curitiba, Parana, Brazil. [Roy, Bidyut] Indian Stat Inst, AHGU, Kolkata 700035, W Bengal, India. [Spitz, Margaret R.; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Strange, Richard C.] Univ Keele, Ctr Cell & Mol Med, Keele ST5 5BG, Staffs, England. [Varela-Lema, Leonor; Ruano-Ravina, Alberto; Barros-Dios, Juan M.] Univ Santiago, Dept Prevent Med & Publ Hlth, Santiago de Compostela, Spain. RP Taioli, E (reprint author), Univ Pittsburgh, Inst Canc, 5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM taiolien@upmc.edu RI Chen, Chien-Jen/C-6976-2008; Goloni-Bertollo, Eny/B-8405-2012; Benhamou, Simone/K-6554-2015; OI Goloni-Bertollo, Eny/0000-0002-2622-4673; Varela-Lema, Leonor/0000-0001-8365-7961; Hayes, Richard/0000-0002-0918-661X; foulkes, william/0000-0001-7427-4651 FU NCI NIH HHS [5P50CA097190, F32 CA073173, P50 CA097190, P50CA097190]; NCRR NIH HHS [1KL2 RR024154-02, KL2 RR024154] NR 120 TC 40 Z9 42 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JUN PY 2008 VL 10 IS 6 BP 369 EP 384 DI 10.1097/GIM.0b013e3181770196 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 316OP UT WOS:000256959900001 PM 18496222 ER PT J AU Akagi, K Li, JF Stephens, RM Volfovsky, N Symer, DE AF Akagi, Keiko Li, Jingfeng Stephens, Robert M. Volfovsky, Natalia Symer, David E. TI Extensive variation between inbred mouse strains due to endogenous L1 retrotransposition SO GENOME RESEARCH LA English DT Article ID COPY NUMBER VARIATION; HUMAN GENOME; LABORATORY MOUSE; GENE-EXPRESSION; CYTOSINE METHYLATION; INSERTION; ELEMENTS; LINE-1; CELLS; MAP AB Numerous inbred mouse strains comprise models for human diseases and diversity, but the molecular differences between them are mostly unknown. Several mammalian genomes have been assembled, providing a framework for identifying structural variations. To identify variants between inbred mouse strains at a single nucleotide resolution, we aligned 26 million individual sequence traces from four laboratory mouse strains to the C57BL/6J reference genome. We discovered and analyzed over 10,000 intermediate-length genomic variants (from 100 nucleotides to 10 kilobases), distinguishing these strains from the C57BL/6J reference. Approximately 85% of such variants are due to recent mobilization of endogenous retrotransposons, predominantly L1 elements, greatly exceeding that reported in humans. Many genes' structures and expression are altered directly by polymorphic L1 retrotransposons, including Drosha (also called Rnasen), Parp8, Scn1a, Arhgap15, and others, including novel genes. L1 polymorphisms are distributed nonrandomly across the genome, as they are excluded significantly from the X chromosome and from genes associated with the cell cycle, but are enriched in receptor genes. Thus, recent endogenous L1 retrotransposition has diversified genomic structures and transcripts extensively, distinguishing mouse lineages and driving a major portion of natural genetic variation. C1 [Li, Jingfeng; Symer, David E.] NCI, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA. [Akagi, Keiko] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Stephens, Robert M.; Volfovsky, Natalia] SAIC Frederick Inc, Adv Technol Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Symer, David E.] NCI, Canc Res Ctr, Biochem & Mol Biol Lab, Frederick, MD 21702 USA. RP Symer, DE (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA. EM symerd@mail.nih.gov RI Symer, David/E-4173-2011 FU Intramural NIH HHS [NIH0011255384, Z01 BC010628-04]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 49 TC 46 Z9 47 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 2008 VL 18 IS 6 BP 869 EP 880 DI 10.1101/gr.075770.107 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 307YT UT WOS:000256356200004 PM 18381897 ER PT J AU Ng, WV Wu, TH Berquist, BR Coker, JA Capes, M DasSarma, P DasSarma, S AF Ng, Wailap Victor Wu, Timothy H. Berquist, Brian R. Coker, James A. Capes, Melinda DasSarma, Priya DasSarma, Shiladitya TI Genome sequences of Halobacterium species SO GENOMICS LA English DT Letter ID GAS VESICLE GENE; HALOPHILIC ARCHAEON; PURPLE MEMBRANE; PLASMID PNRC100; STRAIN NRC-1; HALOBIUM; CLUSTER; IDENTIFICATION; EVOLUTION; MUTANTS C1 [Coker, James A.; Capes, Melinda; DasSarma, Priya; DasSarma, Shiladitya] Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. [Ng, Wailap Victor; Wu, Timothy H.] Natl Yang Ming Univ, Inst Biomed Informat, Dept Biotechnol & Lab Sci Med, Taipei 112, Taiwan. [Berquist, Brian R.] NIA, Unit Struct & Funct Base Excis Repair, NIH, Baltimore, MD 21224 USA. RP DasSarma, S (reprint author), Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, 600 E Lombard St, Baltimore, MD 21202 USA. OI Coker, James/0000-0002-1935-5413 NR 58 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2008 VL 91 IS 6 BP 548 EP 552 DI 10.1016/j.ygeno.2008.04.005 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 315YJ UT WOS:000256915800011 PM 18538726 ER PT J AU Malarkey, EB Ni, Y Parpura, V AF Malarkey, Erik B. Ni, Yingchun Parpura, Vladimir TI Ca(2+) entry through TRPC1 channels contributes to intracellular Ca(2+) dynamics and consequent glutamate release from rat astrocytes SO GLIA LA English DT Article DE store-operated Ca(2+) entry; Ca(2+)-dependent glutamate release; exocytosis; signaling ID CAPACITATIVE CALCIUM-ENTRY; CATION CHANNEL; GLIAL-CELLS; HIPPOCAMPAL ASTROCYTES; CEREBELLAR ASTROCYTES; ENDOPLASMIC-RETICULUM; TRANSMITTER RELEASE; MOUSE ASTROCYTES; IN-SITU; BRAIN AB Astrocytes can respond to a variety of stimuli by elevating their cytoplasmic Ca(2+) concentration and can in turn release glutamate to signal adjacent neurons. The majority of this Ca(2+) is derived from internal stores while a portion also comes from outside of the cell. Astrocytes use Ca(2+) entry through store-operated Ca(2+) channels to refill their internal stores. Therefore, we investigated what role this store-operated Ca(2+) entry plays in astrocytic Ca(2+) responses and subsequent glutamate release. Astrocytes express canonical transient receptor potential (TRPC) channels that have been implicated in mediating store-operated Ca(2+) entry. Here, we show that astrocytes in culture and freshly isolated astrocytes from visual cortex express TRPC1, TRPC4, and TRPC5. Indirect immunocytochemistry reveals that these proteins are present throughout the cell; the predominant expression of functionally tested TRPC1, however, is on the plasma membrane. Labeling in freshly isolated astrocytes reveals changes in TRPC expression throughout development. Using an antibody against TRPC1 we were able to block the function of TRPCI channels and determine their involvement in mechanically and agonist-evoked Ca(2+) entry in cultured astrocytes. Blocking TRPC1 was also found to reduce mechanically induced Ca(2+)-dependent glutamate release. These data indicate that Ca(2+) entry through TRPCI channels contributes to Ca(2+) signaling in astrocytes and the consequent glutamate release from these cells. (C) 2008 Wiley-Liss, Inc. C1 [Malarkey, Erik B.; Parpura, Vladimir] Univ Alabama, Dept Neurol,Evelyn F McKnight Brain Inst, Ctr Glial Biol Med,Civitan Int Res Ctr, Atom Force Microscopy & Nanotechnol Labs, Birmingham, AL 35294 USA. [Ni, Yingchun] NICHHD, NIH, Bethesda, MD 20892 USA. RP Parpura, V (reprint author), Univ Alabama, Dept Neurol,Evelyn F McKnight Brain Inst, Ctr Glial Biol Med,Civitan Int Res Ctr, Atom Force Microscopy & Nanotechnol Labs, 1719 6th Ave S,CIRC 429, Birmingham, AL 35294 USA. EM vlad@uab.edu RI Parpura, Vladimir/A-1242-2010 OI Parpura, Vladimir/0000-0002-4643-2197 FU NIMH NIH HHS [MH 069791] NR 72 TC 100 Z9 101 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD JUN PY 2008 VL 56 IS 8 BP 821 EP 835 DI 10.1002/glia.20656 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 298GU UT WOS:000255675200002 PM 18338793 ER PT J AU Shahjee, H Bhattacharyya, N Zappala, G Wiench, M Prakash, S Rechler, MM AF Shahjee, H. Bhattacharyya, N. Zappala, G. Wiench, M. Prakash, S. Rechler, M. M. TI An N-terminal fragment of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in human prostate cancer cells in an IGF-independent manner SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE IGFBP-3; apoptosis; human prostate cancer cells ID FACTOR BINDING-PROTEIN-3; PROTEOLYTIC FRAGMENT; EPITHELIAL-CELLS; SURFACE BINDING; HEPARIN-BINDING; CARCINOMA CELLS; INHIBITION; SERUM; EXPRESSION; DOMAIN AB Objective: IGF-binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by direct, IGF-independent mechanisms that are poorly understood. IGFBP-3 undergoes limited proteolysis by plasmin and other proteases to generate small N-terminal fragments (e.g., amino acids 1-97) that have lost their affinity for IGF-1 and IGF-II yet still can inhibit mitogenesis. The present study examines whether the N-terminal 1-97-IGFBP-3 fragment can induce apoptosis in human prostate cancer cells in an IGF-independent manner. Design: N-terminal 1-97-IGFBP-3 with or without a signal prepeptide was fused to yellow fluorescent protein (YFP) and expressed in PC-3 human prostate cancer cells. In some cases, the N-terminal IGF-binding site was mutated. Subcellular localization was determined by confocal microscopy. Loss of cell viability was determined by Annexin V-APC staining in the presence and absence of a general caspase inhibitor, z-VAD-fmk. Results: All of the fusion proteins, including those synthesized with a signal peptide, were predominantly intracellular, suggesting that they had been internalized following secretion. YFP-1-97-IGFBP-3 is present at comparable concentrations in the nucleus and cytoplasm, indicating that it does not contain a nuclear localization signal. Cells transfected with YFP-1-97-IGFBP-3 lost viability. Cell death was blocked by incubation with a caspase inhibitor suggesting that it resulted from apoptosis. Similar results were obtained with YFP-1-97-IGFBP-3 mutants that do not bind IGFs. Conclusions: The N-terminal 1-97-IGFBP-3 fragment induces apoptosis in human prostate cancer cells in an IGF independent manner. Generation of the fragment might contribute to the proapoptotic activity of IGFBP-3 in vivo. Published by Elsevier Ltd. C1 [Shahjee, H.; Bhattacharyya, N.; Zappala, G.; Prakash, S.; Rechler, M. M.] NIDDK, NIH, Diabet Branch, Bethesda, MD 20892 USA. [Wiench, M.] NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Rechler, MM (reprint author), NIDDK, NIH, Diabet Branch, Bldg 10 Room 8D12,9000 Rockville Pike,MSC 1758, Bethesda, MD 20892 USA. EM mrechler@helix.nih.gov FU Intramural NIH HHS NR 61 TC 7 Z9 8 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD JUN PY 2008 VL 18 IS 3 BP 188 EP 197 DI 10.1016/j.ghir.2007.08.006 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 297BM UT WOS:000255591100002 PM 17959403 ER PT J AU Jara-Acevedo, M Garcia-Montero, AC Teodosio, C Escribano, L Alvarez, I Sanchez-Munoz, L Akin, C Metcalfe, DD Orfao, A AF Jara-Acevedo, M. Garcia-Montero, A. C. Teodosio, C. Escribano, L. Alvarez, I. Sanchez-Munoz, L. Akin, C. Metcalfe, D. D. Orfao, A. TI WELL-DIFFERENTIATED SYSTEMIC MASTOCYTOSIS (WDSM): A NOVEL FORM OF MASTOCYTOSIS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Jara-Acevedo, M.; Garcia-Montero, A. C.; Teodosio, C.; Orfao, A.] Canc Res Ctr, Salamanca, Spain. [Escribano, L.; Alvarez, I.; Sanchez-Munoz, L.] Ctr Estudios Mastocitosis Castilla Mancha, Toledo, Spain. [Akin, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Metcalfe, D. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2008 VL 93 MA 0226 BP 91 EP 91 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200227 ER PT J AU Bates, S Piekarz, R Frye, R Allen, S Craig, M Geskin, L Hutchins, L Joske, D Kirschbaum, M Leonard, J Prince, M Reeder, C Nichols, J AF Bates, S. Piekarz, R. Frye, R. Allen, S. Craig, M. Geskin, L. Hutchins, L. Joske, D. Kirschbaum, M. Leonard, J. Prince, M. Reeder, C. Nichols, J. TI ROMIDEPSIN INDUCES CLINICALLY SIGNIFICANT AND DURABLE RESPONSES IN RELAPSED OR REFRACTORY CTCL: A NCI INTERNATIONAL, MULTICENTER STUDY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Bates, S.; Piekarz, R.; Frye, R.] NCI, Bethesda, MD 20892 USA. [Allen, S.] N Shore Univ Hosp, Manhasset, NY USA. [Craig, M.] W Virginia Univ, Morgantown, WV 26506 USA. [Geskin, L.] Univ Pittsburgh, Pittsburgh, PA USA. [Hutchins, L.] Arkansas Canc Res Ctr, Little Rock, AR USA. [Joske, D.] Sir Charles Gairdner Hosp, Perth, WA 6000, Australia. [Kirschbaum, M.] City Hope Canc Ctr, Duarte, CA USA. [Leonard, J.] Cornell Univ, New York, NY 10021 USA. [Prince, M.] Peter MacCallum Canc Inst, Melbourne, Australia. [Reeder, C.] Mayo Clin, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2008 VL 93 MA 0435 BP 175 EP 176 PG 2 WC Hematology SC Hematology GA 408JB UT WOS:000263430200436 ER PT J AU Badros, Z Philip, S Niesvizky, R Goloubeva, O Harris, C Zweibel, J Wright, J Burger, A Baer, M Egorin, M Grant, S AF Badros, Z. Philip, S. Niesvizky, R. Goloubeva, O. Harris, C. Zweibel, J. Wright, J. Burger, A. Baer, M. Egorin, M. Grant, S. TI PHASE I TRIAL OF VORINOSTAT PLUS BORTEZOMIB (BORT) IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA (MM) PATIENTS (PTS) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Badros, Z.; Philip, S.; Goloubeva, O.; Harris, C.; Burger, A.; Baer, M.] Univ Maryland, Baltimore, MD 21201 USA. [Niesvizky, R.] Cornell Univ, New York, NY 10021 USA. [Zweibel, J.; Wright, J.] NCI, CTEP, Bethesda, MD 20892 USA. [Egorin, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Grant, S.] Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2008 VL 93 MA 0642 BP 258 EP 258 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200643 ER PT J AU Cunha, A Brugnerotto, AF de Melo, MB Corat, MAF Gimenes, AP Passos, LAC Devlin, EE Bodine, D Saad, STO Costa, FF AF Cunha, A. Brugnerotto, A. F. de Melo, M. B. Corat, M. A. F. Gimenes, A. P. Passos, L. A. C. Devlin, E. E. Bodine, D. Saad, S. T. O. Costa, F. F. TI HIGH LEVELS OF HUMAN GAMMA-GLOBIN ARE EXPRESSED IN ADULT MICE CARRYING A TRANSGENE OF THE BRAZILIAN TYPE OF HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Cunha, A.; Brugnerotto, A. F.; de Melo, M. B.; Corat, M. A. F.; Gimenes, A. P.; Passos, L. A. C.; Saad, S. T. O.; Costa, F. F.] Univ Estadual Campinas, Campinas, SP, Brazil. [Devlin, E. E.; Bodine, D.] NHGRI, Hematopoiesis Sect, Bethesda, MD 20892 USA. RI Corat, Marcus/M-2301-2013 OI Corat, Marcus/0000-0002-8801-2318 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2008 VL 93 MA 0850 BP 337 EP 338 PG 2 WC Hematology SC Hematology GA 408JB UT WOS:000263430201090 ER PT J AU Aue, G Njuguna, N Vire, B Soto, S Boss, C Pittaluga, S Wiestner, AW AF Aue, G. Njuguna, N. Vire, B. Soto, S. Boss, C. Pittaluga, S. Wiestner, A. W. TI LENALIDOMIDE LEADS TO A PRO-INFLAMMATORY CYTOKINE RELEASE SYNDROME IN CLL WHICH MAY HAVE IMPLICATIONS ON THE MANAGEMENT SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Aue, G.; Njuguna, N.; Vire, B.; Soto, S.; Boss, C.; Pittaluga, S.; Wiestner, A. W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2008 VL 93 MA 0983 BP 391 EP 392 PG 2 WC Hematology SC Hematology GA 408JB UT WOS:000263430201222 ER PT J AU Clauser, SB Haffer, SC AF Clauser, Steven B. Haffer, Samuel C. (Chris) TI SEER-MHOS: A new federal collaboration on cancer outcomes research SO HEALTH CARE FINANCING REVIEW LA English DT Editorial Material C1 [Clauser, Steven B.] NCI, EPN, Bethesda, MD 20892 USA. RP Clauser, SB (reprint author), NCI, EPN, 6130 Execut Blvd,Room 4086, Bethesda, MD 20892 USA. EM clausers@mail.nih.gov NR 5 TC 4 Z9 4 U1 0 U2 1 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2008 VL 29 IS 4 BP 1 EP 4 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 339DO UT WOS:000258558500001 PM 18773610 ER PT J AU Ambs, A Warren, JL Bellizzi, KM Topor, M Haffer, SC Clauser, SB AF Ambs, Anita Warren, Joan L. Bellizzi, Keith M. Topor, Marie Haffer, Samuel C. (Chris) Clauser, Steven B. TI Overview of the SEER-Medicare Health Outcomes Survey linked dataset SO HEALTH CARE FINANCING REVIEW LA English DT Article ID CANCER; AGE; SURVIVORS; NATION AB The Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) links cancer registry data with survey data from Medicare managed care enrollees. The linked file includes clinical information about the cancer with self-reported data about symptoms, functional status and health-related quality of life (HRQOL) for Medicare managed care enrollees. This article provides a description of the SEER-MHOS data as a tool to study cancer among Medicare enrollees. In order to highlight the strengths of the database, we also present some descriptive statistics from the database. C1 [Ambs, Anita; Warren, Joan L.; Bellizzi, Keith M.; Clauser, Steven B.] NCI, Bethesda, MD 20892 USA. RP Ambs, A (reprint author), NCI, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM ambsa@mail.nih.gov NR 27 TC 41 Z9 41 U1 2 U2 6 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2008 VL 29 IS 4 BP 5 EP 21 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 339DO UT WOS:000258558500002 PM 18773611 ER PT J AU Clauser, SB Arora, NK Bellizzi, KM Haffer, SC Topor, M Hays, RD AF Clauser, Steven B. Arora, Neeraj K. Bellizzi, Keith M. Haffer, Samuel C. (Chris) Topor, Marie Hays, Ron D. TI Disparities in HRQOL of cancer survivors and non-cancer managed care enrollees SO HEALTH CARE FINANCING REVIEW LA English DT Article ID QUALITY-OF-LIFE; HEALTH-STATUS; PROSTATE-CANCER; MULTIETHNIC SAMPLE; ETHNIC DISPARITIES; BREAST-CARCINOMA; LUNG; MEN AB Health plan member survey and cancer registry data were analyzed to understand differences in health-related quality of life (HRQOL) among cancer survivors and those without a cancer diagnosis enrolled in Medicare managed care. HRQOL was measured by the physical component summary score (PCS) and mental component summary score (MCS) of the Medical Outcomes Study SF-36 (R), version 1.0. Cancer survivors enrolled in Medicare managed care have lower PCS and MCS scores than those enrollees who have never been diagnosed with cancer. PCS scores are worse than the MCS scores, and lowest for cancer survivors who are Hispanic, Medicaid enrollees, and those who have low income or education. HRQOL disparities are greatest among cancer survivors diagnosed with lung cancer and those with multiple primary cancer diagnoses. The influence of these variables persists when controlling for multiple variables including comorbidity status. Health plans should focus on addressing these disparities. C1 [Clauser, Steven B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hays, Ron D.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Clauser, SB (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM clausers@mail.nih.gov RI Hays, Ronald/D-5629-2013 FU National Cancer Institute; National Institute on Aging [AG020679-01]; UCLA [2P30-AG-021684] FX Steven B. Clauser, Neeraj K. Arora, and Keith M. Bellizzi are with the National Cancer Institute (NCI). Samuel C. (Chris) Haffer is with the Centers for Medicare & Medicaid Services (CMS). Marie Topor is with Information Management Services, Inc. Ron D. Hays is with the University of California, Los Angeles (UCLA). He was supported by the National Cancer Institute under the Intergovernmental Personnel Act and in part by a P01 Grant Number AG020679-01 from the National Institute on Aging and by UCLA under Grant Number 2P30-AG-021684. The statements expressed in this article are those of the authors and do not necessarily reflect the views or policies of NCI, CMS, Information Management Services, Inc., or UCLA NR 34 TC 18 Z9 19 U1 2 U2 12 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2008 VL 29 IS 4 BP 23 EP 40 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 339DO UT WOS:000258558500003 PM 18773612 ER PT J AU Smith, AW Reeve, BB Bellizzi, KM Harlan, LC Klabunde, CN Amsellem, M Bierman, AS Hays, RD AF Smith, Ashley Wilder Reeve, Bryce B. Bellizzi, Keith M. Harlan, Linda C. Klabunde, Carrie N. Amsellem, Marni Bierman, Arlene S. Hays, Ron D. TI Cancer, comorbidities, and health-related quality of life of older adults SO HEALTH CARE FINANCING REVIEW LA English DT Article ID PROSTATE-CANCER; OUTCOMES SURVEY; CO-MORBIDITY; DISABILITY; DISEASE; CARE; AGE AB This study examined the physical and mental health of 126,685 males and females age 65 or over, with and without cancer that completed a Medicare Health Outcomes Survey (MHOS) between 1998-2002. Cancer information was ascertained through the National Cancer Institute's (NCI's) Surveillance, Epidemiology and End Results (SEER) program and linked to MHOS data. Results indicated that across most cancer types, cancer patients reported significantly more comorbid conditions and poorer physical and mental health compared with patients without cancer. Negative associations were most pronounced in those with two or more comorbidities and in those diagnosed with cancer within the past year. C1 [Smith, Ashley Wilder; Reeve, Bryce B.; Bellizzi, Keith M.; Harlan, Linda C.; Klabunde, Carrie N.] NCI, Bethesda, MD 20892 USA. [Amsellem, Marni] SAIC Frederick, Frederick, MD USA. [Bierman, Arlene S.] Univ Toronto, Toronto, ON, Canada. [Bierman, Arlene S.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Hays, Ron D.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Smith, AW (reprint author), NCI, 6130 Execut Blvd,MSC 7344,Execut Plaza N,Room 409, Bethesda, MD 20892 USA. EM smithas@mail.nih.gov RI Hays, Ronald/D-5629-2013 FU NCI; National Institute on Aging [AG020679-01]; UCLA Center for Health Improvement in Minority Elderly/Resource Centers for Minority Aging Research [2P30-AG-021684] FX Ashley Wilder Smith, Bryce B. Reeve, Keith M. Beilizzi, Linda C. Harlan, and Carrie N. Klabunde, are with the National Cancer Institute (NCI). Marni S. Amsellem is with SAIC-Frederick. Arlene S. Bierman, M.D., is with the University of Toronto and St. Michael's Hospital, Toronto, Canada. Ron D. Hays is with the University of California, Los Angeles; he was supported by NCI under the Intergovernmental Personnel Act and in part by P01 Grant Number AG020679-01 from the National Institute on Aging and the UCLA Center for Health Improvement in Minority Elderly/Resource Centers for Minority Aging Research under Grant 2P30-AG-021684. The statements expressed in this article are those of the authors and do not reflect the views or policies of NCI, St. Michael's Hospital, Toronto, Canada; National Institute on Aging; University of California, Los Angeles; or the Centers for Medicare & Medicaid Services (CMS). NR 34 TC 78 Z9 78 U1 1 U2 13 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2008 VL 29 IS 4 BP 41 EP 56 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 339DO UT WOS:000258558500004 PM 18773613 ER PT J AU Hays, RD Smith, AW Reeve, BB Spritzer, KL Marcus, SE Clauser, SB AF Hays, Ron D. Smith, Ashley Wilder Reeve, Bryce B. Spritzer, Karen L. Marcus, Stephen E. Clauser, Steven B. TI Cigarette smoking and health-related quality of life in Medicare beneficiaries SO HEALTH CARE FINANCING REVIEW LA English DT Article ID MANAGED CARE ENROLLEES; CANCER; PROGRAM AB This study examined associations between cigarette smoking, cancer, and self-reported physical (SF-36 (R) Physical Component Summary score, [PCS]) and mental health (SF-36 (R) Mental Component Summary Score, [MCS]) among 123,567 Medicare beneficiaries enrolled in managed care plans. As expected for a sample of older individuals, the SF-30 (R) PCS mean (42.6) was lower than the U.S. general population mean of 50. The SF-30 (R) MCS mean (51.7) for the sample was higher than the general population mean. In addition, least squares means revealed significantly poorer health for current smokers and those who recently quit, regardless of their cancer status. Although statistically significant, the differences between current smokers and never smokers were small among those with or without cancer. Encouraging smokers to quit and providing abstinence support to Persons who have recently quit may help reduce health-related impacts of cigarette use. C1 [Hays, Ron D.; Spritzer, Karen L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Smith, Ashley Wilder; Reeve, Bryce B.; Marcus, Stephen E.; Clauser, Steven B.] NCI, Bethesda, MD 20892 USA. RP Hays, RD (reprint author), Univ Calif Los Angeles, Dept Med, 911 Broxton Ave, Los Angeles, CA 90024 USA. EM drhays@ucla.edu RI Hays, Ronald/D-5629-2013 FU National Cancer Institute; National Institute on Aging [AG020679-01]; UCLA Center for Health Improvement in Minority Elderly/Resource Centers for Minority Aging Research [2P30-AG-021684] FX Ron D. Hays and Karen L. Spritzer are with the University of California, Los Angeles. Ashley Wilder Smith, Bryce B. Reeve, Stephen E. Marcus, and Steven B. Clauser are with the National Cancer Institute (NCI). Ron Hays was supported by the National Cancer Institute under the Intergovernmental Personnel Act and in part by a P01 Grant Number AG020679-01 from the National Institute on Aging and the UCLA Center for Health Improvement in Minority Elderly/Resource Centers for Minority Aging Research under Grant Number 2P30-AG-021684. The statements expressed in this article are those of the authors and do not necessarily reflect the views or policies of the University of California, Los Angeles; NCI; National Institute on Aging; or the Centers for Medicare & Medicaid Services (CMS). NR 24 TC 10 Z9 10 U1 0 U2 0 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2008 VL 29 IS 4 BP 57 EP 67 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 339DO UT WOS:000258558500005 PM 18773614 ER PT J AU Reeve, BB Smith, AW Arora, NK Hays, RD AF Reeve, Bryce B. Smith, Ashley Wilder Arora, Neeraj K. Hays, Ron D. TI Reducing bias in cancer research: Application of propensity score matching SO HEALTH CARE FINANCING REVIEW LA English DT Article ID MULTIPLE CONTROLS; ADJUSTMENT; REGRESSION; MEDICARE AB In cancer observational studies, differences between groups on confounding variables may have a significant effect on results when examining health outcomes. This study demonstrates the utility of Propensity score matching to balance a non-cancer and cancer cohort of older adults on multiple relevant covariates. This approach matches cases to controls on a single indicator, the Propensity score, rather than multiple variables. Results indicated that Propensity score matching is an efficient and useful way to create a matched case-control study out of a large cohort study, and allows confidence in the strength of the observed outcomes of the study. C1 [Reeve, Bryce B.; Smith, Ashley Wilder; Arora, Neeraj K.] NCI, Bethesda, MD 20892 USA. [Hays, Ron D.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Reeve, BB (reprint author), NCI, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM reeveb@mail.nih.gov RI Hays, Ronald/D-5629-2013 FU National Cancer Institute; National Institute on Aging [AG020679-01]; UCLA Center for Health Improvement in Minority Elderly/Resource Centers for Minority Aging Research [2P30-AG021684] FX Bryce B. Reeve, Ashley Wilder Smith, and Neeraj K. Arora are with the National Cancer Institute (NCI). Ron D. Hays is with the University of California, Los Angeles. Ron Hays was supported by the National Cancer Institute under the Intergovernmental Personnel Act and in part by a P01 Grant Number AG020679-01 from the National Institute on Aging and the UCLA Center for Health Improvement in Minority Elderly/Resource Centers for Minority Aging Research under Grant Number 2P30-AG021684. The statements expressed in this article are those of the authors and do not necessarily reflect the views or policies of NCI; the University of California, Los Angeles; National Institute on Aging; or the Centers for Medicare & Medicaid Services (CMS). NR 22 TC 18 Z9 18 U1 1 U2 3 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2008 VL 29 IS 4 BP 69 EP 80 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 339DO UT WOS:000258558500006 PM 18773615 ER PT J AU Whitmore, SC Grefsheim, SF Rankin, JA AF Whitmore, Susan C. Grefsheim, Suzanne F. Rankin, Jocelyn A. TI Informationist programme in support of biomedical research: a programme description and preliminary findings of an evaluation SO HEALTH INFORMATION AND LIBRARIES JOURNAL LA English DT Article ID HEALTH-SCIENCES LIBRARY; KNOWLEDGE; SERVICE; MODEL AB Background: The informationist programme at the Library of the National Institutes of Health (NIH) in Bethesda, MD, USA has grown to 14 informationists working with 40 clinical and basic science research teams. Purpose: This case report, intended to contribute to the literature on informationist programmes, describes the NIH informationist programme, including implementation experiences, the informationists' training programme, their job responsibilities and programme outcomes. Brief description: The NIH informationist programme was designed to enhance the library's service capacity. Over time, the steps for introducing the service to new groups were formalized to ensure support by leadership, the team being served and the library. Job responsibilities also evolved from traditional library roles to a wide range of knowledge management activities. The commitment by the informationist, the team and the library to continuous learning is critical to the programme's success. Results/outcomes: NIH scientists reported that informationists saved them time and contributed to teamwork with expert searching and point-of-need instruction. Process evaluation helped refine the programme. Evaluation method: High-level, preliminary outcomes were identified from a survey of scientists receiving informationist services, along with key informant interviews. Process evaluation examined service implementation, informationists' training and service components. Anecdotal evidence has also indicated a favourable response to the programme. C1 [Whitmore, Susan C.] US Natl Inst Hlth, NIH Lib, Informat & Educ Serv Branch, Bethesda, MD 20892 USA. [Rankin, Jocelyn A.] US Ctr Dis Control & Prevent, Publ Hlth Lib & Informat Ctr, Atlanta, GA USA. RP Whitmore, SC (reprint author), US Natl Inst Hlth, NIH Lib, Informat & Educ Serv Branch, Bethesda, MD 20892 USA. EM whitmors@mail.nih.gov FU Intramural NIH HHS [NIH0010119254] NR 17 TC 14 Z9 15 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1471-1834 EI 1471-1842 J9 HEALTH INFO LIBR J JI Heatlth Info. Libr. J. PD JUN PY 2008 VL 25 IS 2 BP 135 EP 141 DI 10.1111/j.1471-1842.2007.00756.x PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 304HK UT WOS:000256100400007 PM 18494648 ER PT J AU Vanwolleghem, T Bukh, J Meuleman, P Desombere, I Meunier, JC Alter, H Purcell, RH Leroux-Roels, G AF Vanwolleghem, Thomas Bukh, Jens Meuleman, Philip Desombere, Isabelle Meunier, Jean-Christophe Alter, Harvey Purcell, Robert H. Leroux-Roels, Geert TI Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain SO HEPATOLOGY LA English DT Article ID IN-VIVO; NEUTRALIZING ANTIBODY; IMMUNE GLOBULIN; CHIMPANZEES; HCV; REPLICATION; PREVENTION; VITRO; TRANSPLANTATION; PSEUDOPARTICLES AB The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these IgG can prevent a de novo HCV infection in vivo and contribute to the control of viremia in infected individuals. We addressed this question with homologous in vivo protection studies in human liver-urokinase-type plasminogen activator (uPA)+/+ severe combined immune deficient (SCID) mice. Chimeric mice were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naive chimeric mice, the inoculum was pre-incubated in vitro at an IgG concentration normally observed in humans. Conclusion: Polyclonal IgG from a patient with a long-standing HCV infection not only displays neutralizing activity in vitro using the HCVpp system, but also conveys sterilizing immunity toward the ancestral HCV strain in vivo, using the human liver-chimeric mouse model. Both experimental systems will be useful tools to identify neutralizing antibodies for future clinical use. C1 [Vanwolleghem, Thomas; Meuleman, Philip; Desombere, Isabelle; Leroux-Roels, Geert] Ghent Univ & Hosp, Ctr Vaccinol, B-9000 Ghent, Belgium. [Bukh, Jens; Meunier, Jean-Christophe; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen N, Denmark. [Meunier, Jean-Christophe] Ecole Normale Super Lyon, INSERM, U758, Human Virol Dept, F-69364 Lyon, France. [Alter, Harvey] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD USA. RP Leroux-Roels, G (reprint author), Ghent Univ & Hosp, Ctr Vaccinol, Bldg A,1st Floor,Pintelaan 185, B-9000 Ghent, Belgium. EM geert.lerouxroels@ugent.be RI Meuleman, Philip/H-2899-2013 OI Meuleman, Philip/0000-0001-6821-234X FU Intramural NIH HHS NR 31 TC 78 Z9 83 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2008 VL 47 IS 6 BP 1846 EP 1855 DI 10.1002/hep.22244 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 308LL UT WOS:000256391500011 PM 18452146 ER PT J AU Coulouarn, C Factor, VM Thorgeirsson, SS AF Coulouarn, Cedric Factor, Valentina M. Thorgeirsson, Snorri S. TI Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; TGF-BETA; FUNCTIONAL GENOMICS; MEMBRANE; MICE; METASTASIS; ACTIVATION; MECHANISMS; PATHWAY; CELLS AB Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The clinical heterogeneity of HCC, and the lack of good diagnostic markers and treatment strategies, has rendered the disease a major challenge. Patients with HCC have a highly variable clinical course, indicating that HCC comprises several biologically distinctive subgroups reflecting a molecular heterogeneity of the tumors. Transforming growth factor beta (TGF-beta) is known to exhibit tumor stage dependent suppressive (that is, growth inhibition) and oncogenic (that is, invasiveness) properties. Here, we asked if a TGF-beta specific gene expression signature could refine the classification and prognostic predictions for HCC patients. Applying a comparative functional genomics approach we demonstrated that a temporal TGF-beta gene expression signature established in mouse primary hepatocytes successfully discriminated distinct subgroups of HCC. The TGF-beta positive duster included two novel homogeneous groups of HCC associated with early and late TGF-beta signatures. Kaplan-Meier plots and log-rank statistics indicated that the patients with a late TGF-beta signature showed significantly (P < 0.005) shortened mean survival time (16.2 +/- 5.3 months) compared to the patients with an early (60.7 +/- 16.1 months) TGF-beta signature. Also, tumors expressing late TGF-beta-responsive genes displayed invasive phenotype and increased tumor recurrence. We also showed that the late TGF-beta signature accurately predicted liver metastasis and discriminated HCC cell lines by degree of invasiveness. Finally, we established that the TGF-beta gene expression signature possessed a predictive value for tumors other than HCC. Conclusion: These data demonstrate the clinical significance of the genes embedded in TGF-beta expression signature for the molecular classification of HCC. C1 [Coulouarn, Cedric; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 4146, Bethesda, MD 20892 USA. EM snorri_s_thorgeirsson@nih.gov RI Coulouarn, Cedric/E-5472-2011 FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 136 Z9 139 U1 2 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2008 VL 47 IS 6 BP 2059 EP 2067 DI 10.1002/hep.22283 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 308LL UT WOS:000256391500032 PM 18506891 ER PT J AU Heyerdahl, SL Boikos, S Horvath, A Giatzakis, C Bossis, I Stratakis, CA AF Heyerdahl, S. L. Boikos, S. Horvath, A. Giatzakis, C. Bossis, I. Stratakis, C. A. TI Protein kinase a subunit expression is altered in bloom syndrome fibroblasts and the BLM protein is increased in adrenocortical hyperplasias: Inverse findings for BLM and PRKAR1A SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE adrenocortical hyperplasia; PRKAR1A; PKA; BLM; Bloom syndrome; adrenal tumors; genomic instability ID TOPOISOMERASE-III-ALPHA; CARNEY COMPLEX; SYNDROME HELICASE; ENDOCRINE; TUMORS; GENE; RECOMBINATION; STABILITY; 17Q22-24; MYXOMAS AB Bloom syndrome is a genetic disorder associated with chromosomal instability and a predisposition to tumors that is caused by germline mutations of the BLM gene, a RecQ helicase. Benign adrenocortical tumors display a degree of chromosomal instability that is more significant than benign tumors of other tissues. Cortisol-producing hyperplasias, such as primary pigmented nodular adrenocortical disease (PPNAD), which has been associated with protein kinase A (PKA) abnormalities and/or PRMR1A mutations, also show genomic instability. Another RecQ helicase, WRN, directly interacts with the PRKAR1B subunit of PKA. In this study, we have investigated the PRKAR1A expression in primary human Bloom syndrome cell lines with known BLM mutations and examined the BLM gene expression in PPNAD and other adrenal tumor tissues. PRMR1A and other protein kinase A (PI(A) subunits were expressed in Bloom syndrome cells and their level of expression differed by subunit and cell type. Overall, fibroblasts exhibited a significant decrease in protein expression of all PKA subunits except for PRKAR1A, a pattern that has been associated with neoplastic transformation in several cell types. The BLM protein was upregulated in PPNAD and other hyperplasias, compared to samples from normal adrenals and normal cortex, as well as samples from cortisol- and aldosterone-producing adenomas (in which BLM was largely absent). These data reveal an inverse relationship between BLM and PRKAR1A: BLM deficiency is associated with a relative excess of PRKAR1A in fibroblasts compared to other PKA subunits; and PRKAR1A deficiency is associated with increased BLM protein in adrenal hyperplasias. C1 [Heyerdahl, S. L.; Boikos, S.; Horvath, A.; Giatzakis, C.; Bossis, I.; Stratakis, C. A.] NICHD, SEGEN, PDEGEN, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, SEGEN, PDEGEN, NIH, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS NR 30 TC 3 Z9 3 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2008 VL 40 IS 6 BP 391 EP 397 DI 10.1055/s-2008-1058089 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323RM UT WOS:000257466100006 PM 18401830 ER PT J AU Macbeth, AH Scharfman, HE MacLusk, NJ Gautreaux, C Luine, VN AF Macbeth, Abbe H. Scharfman, Helen E. MacLusk, Neil J. Gautreaux, Claris Luine, Victoria N. TI Effects of multiparity on recognition memory, monoaminergic neurotransmitters, and brain-derived neurotrophic factor (BDNF) SO HORMONES AND BEHAVIOR LA English DT Article DE reproductive experience; multiparity; recognition memory; monoamines; BDNF ID LONG-TERM-MEMORY; AFFECTS SPATIAL REFERENCE; MEDIAL PREFRONTAL CORTEX; FACTOR MESSENGER-RNA; AGE-RELATED-CHANGES; OLFACTORY-BULB; REPRODUCTIVE EXPERIENCE; MATERNAL-BEHAVIOR; OBJECT RECOGNITION; WORKING-MEMORY AB Recognition memory and anxiety were examined in nulliparous (NP: 0 litters) and multiparous (MP: 5-6 litters) middle-aged female rats (12 months old) to assess possible enduring effects of multiparity at least 3 months after the last litter was weaned. NIP females performed significantly better than NP females on the non-spatial memory task, object recognition, and the spatial memory task, object placement. Anxiety as measured on the elevated plus maze did not differ between groups. Monoaminergic activity and levels were measured in prefrontal cortex, CA1 hippocampus, CA3 hippocampus, and olfactory bulb (013). NP and MP females differed in monoamine concentrations in the 013 only, with MP females having significantly greater concentrations of dopamine and metabolite DOPAC, norepinephrine and metabolite MHPG, and the serotonin metabolite 5-HIAA, as compared to NP females. These results indicate a long-term change in OB neurochemistry as a result of multiparity. Brain-derived neurotrophic factor (BDNF) was also measured in hippocampus (CA1, CA3, dentate gyrus) and septum. MP females had higher BDNF levels in both CA1 and septum; as these regions are implicated in memory performance, elevated BDNF may underlie the observed memory task differences. Thus, MP females (experiencing multiple bouts of pregnancy, birth, and pup rearing during the first year of life) displayed enhanced memory task performance but equal anxiety responses, as compared to NP females. These results are consistent with previous studies showing long-term changes in behavioral function in MP, as compared to NP, rats and suggest that alterations in monoamines and a neurotrophin, BDNF, may contribute to the observed behavioral changes. (C) 2007 Elsevier Inc. All rights reserved. C1 [Macbeth, Abbe H.; Gautreaux, Claris; Luine, Victoria N.] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA. [Macbeth, Abbe H.; Luine, Victoria N.] CUNY, Grad Ctr, New York, NY 10016 USA. [Scharfman, Helen E.] Helen Hayes Hosp, Ctr Neural Recovery & Rehabil Res, W Haverstraw, NY 10993 USA. [MacLusk, Neil J.] Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. RP Macbeth, AH (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, 9000 Rockville Pike,Bldg 49,Room 5A51, Bethesda, MD 20892 USA. EM macbetha@mail.nih.gov OI MacLusky, Neil/0000-0002-9202-0564 FU NCRR NIH HHS [G12 RR003037-22, G12 RR003037, RR-03037]; NIGMS NIH HHS [R25 GM060665, R25 GM060665-08, S06 GM060654, S06 GM060654-070015, S06 GM060654-08, S06-GM-60654]; NINDS NIH HHS [NS 37562, R01 NS037562, R01 NS037562-08, R56 NS037562] NR 83 TC 44 Z9 46 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 0018-506X J9 HORM BEHAV JI Horm. Behav. PD JUN PY 2008 VL 54 IS 1 BP 7 EP 17 DI 10.1016/j.yhbeh.2007.08.011 PG 11 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 313ZT UT WOS:000256779200003 PM 17927990 ER PT J AU Horovitz, SG Fukunaga, M de Zwart, JA van Gelderen, P Fulton, SC Balkin, TJ Duyn, JH AF Horovitz, Silvina G. Fukunaga, Masaki de Zwart, Jacco A. van Gelderen, Peter Fulton, Susan C. Balkin, Thomas J. Duyn, Jeff H. TI Low frequency BOLD fluctuations during resting wakefulness and light sleep: A simultaneous EEG-fMRI study SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; EEG; sleep; resting state; functional connectivity; low frequency fluctuations; default-mode network; visual cortex ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; INDEPENDENT COMPONENT ANALYSIS; EYE-MOVEMENT SLEEP; FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; VISUAL-CORTEX; DEFAULT MODE; ALPHA-RHYTHM; RETICULAR-FORMATION AB Recent blood oxygenation level dependent functional MRI (BOLD fMRI) studies of the human brain have shown that in the absence of external stimuli, activity persists in the form of distinct patterns of temporally correlated signal fluctuations. In this work, we investigated the spontaneous BOLD signal fluctuations during states of reduced consciousness such as drowsiness and sleep. For this purpose, we performed BOLD fMRI on normal subjects during varying levels of consciousness, from resting wakefulness to light (non-slow wave) sleep. Depth of sleep was determined based on concurrently acquired EEG data. During light sleep, significant increases in the fluctuation level of the BOLD signal were observed in several cortical areas, among which visual cortex was the most significant. Correlations among brain regions involved with the default-mode network persisted during light sleep. These results suggest that activity in areas such as the default-mode network and primary sensory cortex, as measured from BOLD fMRI fluctuations, does not require a level of consciousness typical of wakefulness. C1 [Horovitz, Silvina G.; Fukunaga, Masaki; de Zwart, Jacco A.; van Gelderen, Peter; Fulton, Susan C.; Duyn, Jeff H.] NINDS, Adv MRI Sect, LFMI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Balkin, Thomas J.] Walter Reed Army Inst Res, Dept Behav Biol, Silver Spring, MD USA. RP Horovitz, SG (reprint author), 9000 Rockville Pike,Bldg 10,Room B1D722, Bethesda, MD 20814 USA. EM silvina.horovitz@nih.gov RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 FU Intramural NIH HHS NR 70 TC 244 Z9 247 U1 3 U2 28 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2008 VL 29 IS 6 BP 671 EP 682 DI 10.1002/hbm.20428 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 311OM UT WOS:000256609500005 PM 17598166 ER PT J AU Rismanchi, N Soderblom, C Stadler, J Zhu, PP Blackstone, C AF Rismanchi, Neggy Soderblom, Cynthia Stadler, Julia Zhu, Peng-Peng Blackstone, Craig TI Atlastin GTPases are required for Golgi apparatus and ER morphogenesis SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; ENDOPLASMIC-RETICULUM; LIVING CELLS; GROWTH CONES; SPG3A; MUTATIONS; ONSET; TRANSPORT; PATHWAY; MICROTUBULES AB The hereditary spastic paraplegias (SPG1-33) comprise a cluster of inherited neurological disorders characterized principally by lower extremity spasticity and weakness due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. Mutations in the gene encoding the large oligomeric GTPase atlastin-1 are responsible for SPG3A, a common autosomal dominant hereditary spastic paraplegia. Here we describe a family of human GTPases, atlastin-2 and -3 that are closely related to atlastin-1. Interestingly, while atlastin-1 is predominantly localized to vesicular tubular complexes and cis-Golgi cisternae, mostly in brain, atlastin-2 and -3 are localized to the endoplasmic reticulum (ER) and are most enriched in other tissues. Knockdown of atlastin-2 and -3 levels in HeLa cells using siRNA (small interfering RNA) causes disruption of Golgi morphology, and these Golgi structures remain sensitive to brefeldin A treatment. Interestingly, expression of SPG3A mutant or dominant-negative atlastin proteins lacking GTPase activity causes prominent inhibition of ER reticularization, suggesting a role for atlastin GTPases in the formation of three-way junctions in the ER. However, secretory pathway trafficking as assessed using vesicular stomatitis virus G protein fused to green fluorescent protein (VSVG-GFP) as a reporter was essentially normal in both knockdown and dominant-negative overexpression conditions for all atlastins. Thus, the atlastin family of GTPases functions prominently in both ER and Golgi morphogenesis, but they do not appear to be required generally for anterograde ER-to-Golgi trafficking. Abnormal morphogenesis of the ER and Golgi resulting from mutations in atlastin-1 may ultimately underlie SPG3A by interfering with proper membrane distribution or polarity of the long corticospinal motor neurons. C1 [Rismanchi, Neggy; Soderblom, Cynthia; Stadler, Julia; Zhu, Peng-Peng; Blackstone, Craig] NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. [Rismanchi, Neggy] Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. [Soderblom, Cynthia] Karolinska Inst, Dept Neurosci, Natl Inst Hlth, Grad Partnerships Program, S-17177 Stockholm, Sweden. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, NIH, Bldg 35,Room 2C-913,35 Convent Dr, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Intramural NIH HHS NR 36 TC 91 Z9 98 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2008 VL 17 IS 11 BP 1591 EP 1604 DI 10.1093/hmg/ddn046 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 305IE UT WOS:000256170800008 PM 18270207 ER PT J AU Xue, YT Li, YJ Guo, R Ling, C Wang, WD AF Xue, Yutong Li, Yongjiang Guo, Rong Ling, Chen Wang, Weidong TI FANCM of the Fanconi anemia core complex is required for both monoubiquitination and DNA repair SO HUMAN MOLECULAR GENETICS LA English DT Article ID DAMAGED REPLICATION FORKS; PROMOTES BRANCH MIGRATION; HOLLIDAY JUNCTIONS; HOMOLOGOUS RECOMBINATION; ESCHERICHIA-COLI; HELICASE BRIP1; RAD54 PROTEIN; X-RAY; PATHWAY; GENE AB In response to DNA damage, the Fanconi anemia (FA) core complex functions as a signaling machine for monoubiquitination of FANCD2 and FANCI. It remains unclear whether this complex can also participate in subsequent DNA repair. We have shown previously that the FANCM constituent of the complex contains a highly conserved helicase domain and an associated ATP-dependent DNA translocase activity. Here we show that FANCM also possesses an ATP-independent binding activity and an ATP-dependent bi-directional branch-point translocation activity on a synthetic four-way junction DNA, which mimics intermediates generated during homologous recombination or at stalled replication forks. Using an siRNA-based complementation system, we found that the ATP-dependent activities of FANCM are required for cellular resistance to a DNA-crosslinking drug, mitomycin C, but not for the monoubiquitination of FANCD2 and FANCI. In contrast, monoubiquitination requires the entire helicase domain of FANCM, which has both ATP dependent and independent activities. These data are consistent with participation of FANCM and its associated FA core complex in the FA pathway at both signaling through monoubiquitination and the ensuing DNA repair. C1 [Xue, Yutong; Li, Yongjiang; Guo, Rong; Ling, Chen; Wang, Weidong] NIA, Natl Inst Hlth, Genet Lab, Baltimore, MD 21224 USA. RP Wang, WD (reprint author), NIA, Natl Inst Hlth, Genet Lab, 333 Cassell Dr,TRIAD Ctr Room 3000, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov FU Intramural NIH HHS NR 46 TC 63 Z9 63 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2008 VL 17 IS 11 BP 1641 EP 1652 DI 10.1093/hmg/ddn054 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 305IE UT WOS:000256170800013 PM 18285517 ER PT J AU Milhavet, F Cuisset, L Hoffman, HM Slim, R El-Shanti, H Aksentijevich, I Lesage, S Waterham, H Wise, C de Menthiere, CS Touitou, I AF Milhavet, Florian Cuisset, Laurence Hoffman, Hal M. Slim, Rima El-Shanti, Hatem Aksentijevich, Ivona Lesage, Suzanne Waterham, Hans Wise, Carol de Menthiere, Cyril Sarrauste Touitou, Isabelle TI The infevers autoinflammatory mutation online registry: Update with new genes and functions SO HUMAN MUTATION LA English DT Article DE autoinflammatory disease; registry; infevers; MEFV; MVK; TNFRSF1A; NLRP3; NOD2; PSTPIP1; LPIN2; NLRP7 ID MULTIFOCAL OSTEOMYELITIS; MAJEED-SYNDROME; FEVER; ASSOCIATION; DISORDERS; SYNDROME/; PROTEIN; PATHWAY; DISEASE; LPIN2 AB Infevers (Internet Fevers; http://fmf.igh.cnrs.fr/ISSAID/infevers), a website dedicated to mutations responsible for hereditary autoinflammatory diseases, was created in 2002 and has continued to evolve. This new version includes eight genes; six were already present: MEFV, NVK, TNFRSF1A, NLRP3, NOD2, PSTPIP1, and two are new, LPIN2 and NLRP7. Currently, Infevers contains over 540 sequence variants. Several new database functions were recently instituted. The website now accepts confidential data and complex alleles. For each gene, a newly created menu offers: 1) a tabular list of the variants that can be sorted by several parameters; 2) a gene graph providing a schematic representation of the variants along the gene; 3) statistical analysis of the data according to the phenotype, alteration type, and location of the mutation in the gene; 4) the cDNA and gDNA sequences of each gene, showing the nucleotide changes along the sequence, with a color-based code highlighting the gene domains, the first ATG, and the termination codon; and 5) a "download" menu making all tables and figures available for the users, which, except for the gene graphs, are all automatically generated and updated upon submission of the variants. Finally, the entire database was curated to comply with the HUGO Gene Nomenclature Committee (HGNC) and HGVS nomenclature guidelines, and wherever necessary, an informative note was provided. Infevers has already proven useful for the scientific community with a mean number of visits per month of 200 in 2002 and 800 in 2007, and its new design will lead to a more comprehensive comparative analysis and interpretation of auto, inflammatory sequence variants. C1 [Touitou, Isabelle] Hop Arnaud de Villeneuve, Unite Med Malad Autoinflammatories, CHU Montpellier, F-34295 Montpellier, France. [Milhavet, Florian; de Menthiere, Cyril Sarrauste; Touitou, Isabelle] CNRS, UPR 1142, Inst Human Genet, Montpellier, France. [Cuisset, Laurence] Hop Cochin, Biochim Genet Lab, F-75674 Paris, France. [Hoffman, Hal M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Slim, Rima] McGill Univ, Ctr Hlth, Res Inst, Dept Human Genet Obstet & Gynecol, Montreal, PQ, Canada. [El-Shanti, Hatem] Univ Iowa, Childrens Hosp, Div Med Genet, Iowa City, IA USA. [Aksentijevich, Ivona] NIAMSD, NIH, Bethesda, MD 20892 USA. [Lesage, Suzanne] Grp Hosp Pitie Salpetriere, Lab Neurol & Therapeut Expt, INSERM, U679, F-75634 Paris, France. [Waterham, Hans] Emma Childrens Hosp, Amsterdam, Netherlands. [Waterham, Hans] Univ Amsterdam, Acad Med Ctr, Lab Genet Metab Dis, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands. [Wise, Carol] Texas Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA. RP Touitou, I (reprint author), Hop Arnaud de Villeneuve, Unite Med Malad Autoinflammatories, CHU Montpellier, F-34295 Montpellier, France. EM isabelle.touitou@igh.cnrs.fr RI EL-SHANTI, HATEM/Q-4932-2016; OI EL-SHANTI, HATEM/0000-0001-6230-8316; Wise, Carol/0000-0002-6790-2194 FU NIAID NIH HHS [R01 AI052430] NR 19 TC 112 Z9 117 U1 1 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2008 VL 29 IS 6 BP 803 EP 808 DI 10.1002/humu.20720 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 311OK UT WOS:000256609300005 PM 18409191 ER PT J AU Granados, EL Keenan, JE Kinney, MC Leo, H Jain, N Ma, CA Quinones, R Gelfand, EW Jain, A AF Granados, Eduardo Lopez Keenan, Jeffrey E. Kinney, Matthew C. Leo, Harvey Jain, Neal Ma, Chi A. Quinones, Ralph Gelfand, Erwin W. Jain, Ashish TI A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency SO HUMAN MUTATION LA English DT Article DE primary immunodeficiency; ectodermal dysplasia; EDI; lymphocyte activation; antigen presenting cell; NEMO; NF-kappa B; IKBKG; I kappa B alpha; IKBA; NFKBIA ID KAPPA-B-ALPHA; IMMUNE-DEFICIENCY; TRANSLATION; NEMO; REINITIATION; INITIATION; LEADS AB Alterations in nuclear factor kappa B (NF-kappa B) essential modulator (NEMO; HUGO-approved symbol IKBKG) underlie most cases of ectodermal dysplasia with immune deficiency (EDI), a human disorder characterized by anhidrosis with diminished immunity. EDI has also been associated with a single heterozygous mutation at position Ser32 of the NF-kappa B inhibitor I kappa B alpha, one of two phosphorylation sites that are essential for targeting I kappa B alpha for proteasomal degradation and hence for activation of NF-kappa B. We report a novel heterozygous nonsense mutation in the IKBA (HUGO-approved symbol, NFKBIA) gene of a I year,old male child with EDI that introduces a premature termination codon at position Glu14. An in-frame methionine downstream of the nonsense mutation allows for reinitiation of translation. The resulting N-terminally truncated protein lacks both serine phosphorylation sites and inhibits NF-kappa B signaling by functioning as a dominant negative on NF-kappa B activity in lymphocytes and monocytes. These findings support the scanning model for translation initiation in eukaryotes and confirm the critical role of the NF-kappa B in the human immune response. C1 [Jain, Ashish] NIAID, Host Def Lab, NIH, CRC, Bethesda, MD 20892 USA. [Leo, Harvey; Jain, Neal; Gelfand, Erwin W.] Natl Jewish Med & Res Ctr, Div Allergy Immunol, Denver, CO USA. [Leo, Harvey; Jain, Neal; Gelfand, Erwin W.] Natl Jewish Med & Res Ctr, Div Cell Biol, Denver, CO USA. [Quinones, Ralph] Childrens Hosp, Div Hematol Oncol, Denver, CO 80218 USA. RP Jain, A (reprint author), NIAID, Host Def Lab, NIH, CRC, 10 Ctr Dr,Rm 5W3950, Bethesda, MD 20892 USA. EM ajain@niaid.nih.gov NR 23 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2008 VL 29 IS 6 BP 861 EP 868 DI 10.1002/humu.20740 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 311OK UT WOS:000256609300011 ER PT J AU Xu, X Fassett, J Hu, XL Zhu, GS Lu, ZB Li, YF Schnermann, J Bache, RJ Chen, YJ AF Xu, Xin Fassett, John Hu, Xinli Zhu, Guangshuo Lu, Zhongbing Li, Yunfang Schnermann, Jurgen Bache, Robert J. Chen, Yingjie TI Ecto-5'-nucleotidase deficiency exacerbates pressure-overload-induced left ventricular hypertrophy and dysfunction SO HYPERTENSION LA English DT Article DE hypertrophy; heart failure; fibrosis; 5'-nucleotidase; adenosine ID A(2B) ADENOSINE RECEPTORS; CONGESTIVE-HEART-FAILURE; CARDIAC-HYPERTROPHY; MICE; CARDIOPROTECTION; OVEREXPRESSION; CONTRACTILITY; FIBROBLASTS; INHIBITION; ACTIVATION AB This study examined whether endogenous extracellular adenosine acts to facilitate the adaptive response of the heart to chronic systolic overload. To examine whether endogenous extracellular adenosine can protect the heart against pressure-overload-induced heart failure, transverse aortic constriction was performed on mice deficient in extracellular adenosine production as the result of genetic deletion of CD73. Although there was no difference in left ventricular size or function between CD73-deficient mice (knockout [KO] mice) and wild-type mice under unstressed conditions, aortic constriction for 2 or 4 weeks induced significantly more myocardial hypertrophy, left ventricular dilation, and left ventricular dysfunction in KO mice compared with wild-type mice. Thus, after 2 weeks of transverse aortic constriction, left ventricular fractional shortening decreased to 27.4 +/- 2.5% and 21.9 +/- 1.7% in wild-type and KO mice, respectively (P < 0.05). Consistent with a role of adenosine in reducing tissue remodeling, KO mice displayed increased myocardial fibrosis and myocyte hypertrophy compared with wild-type mice. Furthermore, adenosine treatment reduced phenyl-ephrine-induced cardiac myocyte hypertrophy and collagen production in cultured neonatal rat cardiac myocytes and cardiac fibroblasts, respectively. Consistent with a role for adenosine in modulating cardiomyocyte hypertrophy, KO mice demonstrated increased activation of mammalian target of rapamycin signaling, accompanied by higher expression of the hypertrophy marker atrial natriuretic peptide. Conversely, the adenosine analogue 2-chloro-adenosine significantly reduced cell size, mammalian target of rapamycin/p70 ribosomal S6 kinase activation, and atrial natriuretic peptide expression in cultured neonatal cardiomyocytes. These data demonstrate that CD73 helps to preserve cardiac function during chronic systolic overload by preventing maladaptive tissue remodeling. C1 [Xu, Xin; Fassett, John; Li, Yunfang; Bache, Robert J.; Chen, Yingjie] Univ Minnesota, Sch Med, Dept Med,Div Cardiovasc, Minneapolis, MN 55455 USA. [Hu, Xinli; Zhu, Guangshuo; Lu, Zhongbing; Chen, Yingjie] Univ Minnesota, Sch Med, Dept Med,Vasc Biol Ctr, Minneapolis, MN 55455 USA. [Schnermann, Jurgen] NIDDKD, NIH, Bethesda, MD USA. RP Chen, YJ (reprint author), Univ Minnesota, Sch Med, Dept Med,Div Cardiovasc, MMC-508,420 Delaware St SE, Minneapolis, MN 55455 USA. EM chenx106@tc.umn.edu OI Lu, Zhongbing/0000-0002-2717-4698; Fassett, John/0000-0003-4591-6875 FU NHLBI NIH HHS [R01 HL071790-03, R01 HL071790-02, R01 HL071790-01A1, R01 HL021872, R01 HL071790, HL71790, R01 HL071790-04, HL21872] NR 36 TC 26 Z9 26 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2008 VL 51 IS 6 BP 1557 EP 1564 DI 10.1161/HYPERTENSIONAHA.108.110833 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 303PT UT WOS:000256053500028 PM 18391093 ER PT J AU Schnabel, R Larson, MG Dupuis, J Lunetta, KL Lipinska, I Meigs, JB Yin, XY Rong, J Vita, JA Newton-Cheh, C Levy, D Keaney, JF Vasan, RS Mitchell, GF Benjamin, EJ AF Schnabel, Renate Larson, Martin G. Dupuis, Josee Lunetta, Kathryn L. Lipinska, Izabella Meigs, James B. Yin, Xiaoyan Rong, Jian Vita, Joseph A. Newton-Cheh, Christopher Levy, Daniel Keaney, John F., Jr. Vasan, Ramachandran S. Mitchell, Gary F. Benjamin, Emelia J. TI Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection SO HYPERTENSION LA English DT Article DE tonometry; inflammation; epidemiology; polymorphism; single nucleotide; genetics ID C-REACTIVE-PROTEIN; SERUM OSTEOPROTEGERIN LEVELS; SYSTEMIC INFLAMMATION; MENDELIAN RANDOMIZATION; ESSENTIAL-HYPERTENSION; JAPANESE SUBJECTS; AORTIC STIFFNESS; BLOOD-PRESSURE; OLDER-ADULTS; HEALTHY-MEN AB Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained < 1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P < 0.01) were as follows: tumor necrosis factor receptor-II ( inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate < 0.50) were observed for rs10509561 (FAS), P=6.6x10(-5) for central pulse pressure and rs11559271 (ITGB2), P=1.1x10(-4) for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures. C1 [Schnabel, Renate; Larson, Martin G.; Dupuis, Josee; Lunetta, Kathryn L.; Lipinska, Izabella; Newton-Cheh, Christopher; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Dupuis, Josee; Lunetta, Kathryn L.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Evans Mem Dept Med, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Dept Prevent Med, Sch Med, Boston, MA 02215 USA. [Levy, Daniel] Ctr Populat Studies, NHLBI, Bethesda, MD USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA. [Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Cambridge, MA USA. [Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Vita, Joseph/0000-0001-5607-1797; Lunetta, Kathryn/0000-0002-9268-810X; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [M01 RR001066, M01 RR001066-26, M01-RR-01066]; NHLBI NIH HHS [R01 HL077447, HL04334, HL064753, HL076784, HL077447, HL080025, HL080124, HL60040, HL70139, K23 HL080025, K23 HL080025-05, K24 HL004334, K24 HL004334-08, N01 HC025195, N01-HC-25195, N01HC25195, R01 HL060040, R01 HL060040-04, R01 HL064753, R01 HL064753-04, R01 HL071039, R01 HL071039-02, R01 HL076784, R01 HL076784-05, R01 HL077447-05, R01 HL080124, R01 HL080124-05, U01 HL066582, U01 HL066582-04S1, U01-HL66582]; NIA NIH HHS [AG028321, R01 AG028321, R01 AG028321-04]; NIDDK NIH HHS [K24 DK080140-01] NR 48 TC 82 Z9 88 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2008 VL 51 IS 6 BP 1651 EP 1657 DI 10.1161/HYPERTENSIONAHA.107.105668 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 303PT UT WOS:000256053500042 PM 18426996 ER PT J AU Koay, CG Nevo, U Chang, LC Pierpaoli, C Basser, PJ AF Koay, Cheng Guan Nevo, Uri Chang, Lin-Ching Pierpaoli, Carlo Basser, Peter J. TI The elliptical cone of uncertainty and its normalized measures in diffusion tensor imaging SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE cone of uncertainty; diffusion tensor imaging (DTI); eigenvector dispersion; normalized areal measure; normalized circumferential measure ID WHITE-MATTER TRACTOGRAPHY; DT-MRI DATA; HUMAN BRAIN; WATER DIFFUSION; FRAMEWORK; CONNECTIVITY; ANISOTROPY; TRACKING; NOISE; ORIENTATION AB Diffusion tensor magnetic resonance imaging (DT-MRI) is capable of providing quantitative insights into tissue microstructure in the brain. An important piece of information offered by DT-MRI is the directional preference of diffusing water molecules within a voxel. Building upon this local directional information, DT-MRI tractography attempts to construct global connectivity of white matter tracts. The interplay between local directional information and global structural information is crucial in understanding changes in tissue microstructure as well as in white matter tracts. To this end, the right circular cone of uncertainty was proposed by Basser as a local measure of tract dispersion. Recent experimental observations by Jeong et al. and Lazar et al. that the cones of uncertainty in the brain are mostly elliptical motivate the present study to investigate analytical approaches to quantify their findings. Two analytical approaches for constructing the elliptical cone of uncertainty, based on the first-order matrix perturbation and the error propagation method via diffusion tensor representations, are presented and their theoretical equivalence is established. We propose two normalized measures, circumferential and areal, to quantify the uncertainty of the major eigenvector of the diffusion tensor. We also describe a new technique of visualizing the cone of uncertainty in 3-D. C1 [Koay, Cheng Guan; Nevo, Uri; Chang, Lin-Ching; Pierpaoli, Carlo; Basser, Peter J.] NICHHD, NIH, Bethesda, MD 20892 USA. [Chang, Lin-Ching] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA. RP Koay, CG (reprint author), NICHHD, NIH, 13 S Dr, Bethesda, MD 20892 USA. EM guankoac@mail.nih.gov RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 FU Intramural NIH HHS [ZIA HD000266-12] NR 47 TC 23 Z9 23 U1 3 U2 3 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 JUN PY 2008 VL 27 IS 6 BP 834 EP 846 DI 10.1109/TMI.2008.915663 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 307YD UT WOS:000256354600010 PM 18541490 ER PT J AU Lev, A Takeda, K Zanker, D Maynard, JC Dimberu, P Waffarn, E Gibbs, J Netzer, N Princiotta, MF Neckers, L Picard, D Nicchitta, CV Chen, W Reiter, Y Bennink, JR Yewdelll, JW AF Lev, Avital Takeda, Kazuyo Zanker, Damien Maynard, Jason C. Dimberu, Peniel Waffarn, Elizabeth Gibbs, James Netzer, Nir Princiotta, Michael F. Neckers, Len Picard, Didier Nicchitta, Christopher V. Chen, Weisan Reiter, Yoram Bennink, Jack R. Yewdelll, Jonathan W. TI The exception that reinforces the rule: Crosspriming by cytosolic peptides that escape degradation SO IMMUNITY LA English DT Article ID MHC CLASS-I; HEAT-SHOCK PROTEINS; COMPLEX-RESTRICTED SPECIFICITY; CYTOTOXIC T-LYMPHOCYTES; CROSS-PRESENTATION; ENDOPLASMIC-RETICULUM; IMMUNODOMINANCE HIERARCHY; RECOMBINANT ANTIBODIES; ANTIGEN PRESENTATION; PRESENTING CELLS AB The nature of crosspriming immunogens for CD8(+) T cell responses is highly controversial. By using a panel of T cell receptor-like antibodies specific for viral peptides bound to mouse D-b major histocompatibility complex class I molecules, we show that an exceptional peptide (PA(224-233)) expressed as a viral minigene product formed a sizeable cytosolic pool continuously presented for hours after protein synthesis was inhibited. PA224-233 pool formation required active cytosolic heat-shock protein 90 but not ER g96 and uniquely enabled crosspriming by this peptide. These findings demonstrate that exceptional class I binding oligopeptides that escape proteolytic degradation are potent crosspriming agents. Thus, the feeble immunogenicity of natural proteasome products in crosspriming can be attributed to their evanescence in donor cells and not an absolute inability of cytosolic oligopeptides to be transferred to and presented by professional antigen-presenting cells. C1 [Lev, Avital; Takeda, Kazuyo; Dimberu, Peniel; Waffarn, Elizabeth; Gibbs, James; Netzer, Nir; Bennink, Jack R.; Yewdelll, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zanker, Damien; Chen, Weisan] Ludwig Inst Canc Res, Melbourne Ctr Clin Sci, T Cell Lab, Heidelberg, Vic 3084, Australia. [Maynard, Jason C.; Nicchitta, Christopher V.] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. [Princiotta, Michael F.] SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. [Picard, Didier] Univ Geneva, Dept Biol Cellulaire, CH-1211 Geneva, Switzerland. [Reiter, Yoram] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel. RP Yewdelll, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012; OI Zanker, Damien/0000-0003-1163-9902 FU Intramural NIH HHS [Z01 AI000542-20, Z01 AI000653-16, Z01 AI000658-16, Z01 AI000814-11] NR 44 TC 38 Z9 38 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2008 VL 28 IS 6 BP 787 EP 798 DI 10.1016/j.immuni.2008.04.015 PG 12 WC Immunology SC Immunology GA 313SL UT WOS:000256760200010 PM 18549799 ER PT J AU Chaturvedi, A Dorward, D Pierce, SK AF Chaturvedi, Akanksha Dorward, David Pierce, Susan K. TI The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-Containing antigens SO IMMUNITY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; ISOLATED RAT HEPATOCYTES; PHOSPHOLIPASE-D; CPG-DNA; MOLECULAR-MECHANISMS; SIGNAL-TRANSDUCTION; ACQUIRED-IMMUNITY; CROSS-LINKING; BACTERIAL-DNA; KAPPA-B AB Synergistic engagement of the B cell receptor (BCR) and Toll-like receptor 9 (TLR9) in response to DNA-containing antigens underlies the production of many autoantibodies in systemic autoimmune diseases. However, the molecular basis of this synergistic engagement is not known. Given that these receptors are spatially segregated, with the BCR on the cell surface and TLR9 in endocytic vesicles, achieving synergy must involve unique mechanisms. We show that upon antigen binding, the BCR initiates signaling at the plasma membrane and continues to signal to activate MAP kinases as it traffics to autophagosome-like compartments. The internalized BCR signals through a phospholipase-D-dependent pathway to recruit TLR9-containing endosomes to the autophagosome via the microtubular network. The recruitment of TLR9 to the autophagosomes was necessary for hyperactivation of MAP kinases. This unique mechanism for BCR-induced TLR9 recruitment resulting in B cells hyperresponses may provide new targets for therapeutics for autoimmune diseases. C1 [Chaturvedi, Akanksha; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Dorward, David] NIAID, Microscopy Unit, Rocky Mt Labs, Res Technol Sec,NIH, Hamilton, MT 59840 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM spierce@nih.gov FU Intramural NIH HHS [Z01 AI000899-07] NR 49 TC 168 Z9 172 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2008 VL 28 IS 6 BP 799 EP 809 DI 10.1016/j.immuni.2008.03.019 PG 11 WC Immunology SC Immunology GA 313SL UT WOS:000256760200011 PM 18513998 ER PT J AU Sette, A Moutaftsi, M Moyron-Quiroz, J McCausland, MM Davies, DH Johnston, RJ Peters, L Benhnia, MREI Hoffmann, J Su, HP Singh, K Garboczi, DN Head, S Grey, H Felgner, PL Crotty, S AF Sette, Alessandro Moutaftsi, Magdalini Moyron-Quiroz, Juan McCausland, Megan M. Davies, D. Huw Johnston, Robert J. Peters, Ljoem Benhnia, Mohammed Rafii-El-Idrissi Hoffmann, Julia Su, Hua-Poo Singh, Kavita Garboczi, David N. Head, Steven Grey, Howard Felgner, Philip L. Crotty, Shane TI Selective CD4(+) T cell help for antibody responses to a large viral pathogen: Deterministic linkage of specificities SO IMMUNITY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; NODE B-CELLS; VACCINIA VIRUS; DENDRITIC CELLS; SMALLPOX VACCINE; LYMPH-NODES; NEUTRALIZING ANTIBODIES; SUBCAPSULAR SINUS; PROTECT MICE; ANTIGEN AB Antibody responses are critical components of protective immune responses to many pathogens, but parameters determining which proteins are targeted remain unclear. Vaccination with individual MHC-II-restricted vaccinia virus (VACV, smallpox vaccine) epitopes revealed that CD4(+) T cell help to B cells was surprisingly nontransferable to other virion protein specificities. Many VACV CD4(+) T cell responses identified in an unbiased screen targeted antibody virion protein targets, consistent with deterministic linkage between specificities. We tested the deterministic linkage model by efficiently predicting new vaccinia MHC II epitopes (830% improved efficiency). Finally, we showed CD4(+) T cell help was limiting for neutralizing antibody development and protective immunity in vivo. In contrast to the standard model, these data indicate individual proteins are the unit of B cell-T cell recognition for a large virus. Therefore, MHC restriction is a key selective event for the antiviral antibody response and is probably important for vaccine development to large pathogens. C1 [Sette, Alessandro; Moutaftsi, Magdalini; Moyron-Quiroz, Juan; McCausland, Megan M.; Johnston, Robert J.; Peters, Ljoem; Benhnia, Mohammed Rafii-El-Idrissi; Grey, Howard; Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. [Davies, D. Huw; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92697 USA. [Hoffmann, Julia; Head, Steven] Scripps Res Inst, DNA Array Core Facil, La Jolla, CA 92037 USA. [Hoffmann, Julia; Head, Steven] Scripps Res Inst, Consortium Funct Glyc, La Jolla, CA 92037 USA. [Su, Hua-Poo; Singh, Kavita; Garboczi, David N.] NIAAA, Struct Biol Sect, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA. RP Crotty, S (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. EM shane@liai.org RI rafii el idrissi benhnia, mohammed/F-3019-2015 OI rafii el idrissi benhnia, mohammed/0000-0001-7405-9476 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI063107-01A1, R01 AI063107-02, R01 AI063107-04, U01 AI077953-01, R01 AI063107, U01 AI077953, R01 AI063107-03]; PHS HHS [HHSN266200400024] NR 55 TC 97 Z9 97 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2008 VL 28 IS 6 BP 847 EP 858 DI 10.1016/j.immuni.2008.04.018 PG 12 WC Immunology SC Immunology GA 313SL UT WOS:000256760200015 PM 18549802 ER PT J AU Chen, Z O'Shea, JJ AF Chen, Zhi O'Shea, John J. TI Th17 cells: a new fate for differentiating helper T cells SO IMMUNOLOGIC RESEARCH LA English DT Review DE T cells; cytokines; interleukins; immunoregulation; Th1; Th2; Th17; regulatory T cells ID GROWTH-FACTOR-BETA; INFLAMMATORY-BOWEL-DISEASE; CENTRAL-NERVOUS-SYSTEM; AUTOIMMUNE ENCEPHALOMYELITIS; CUTTING EDGE; TGF-BETA; NEUTROPHIL RECRUITMENT; INTERLEUKIN-17 FAMILY; RHEUMATOID-ARTHRITIS; INCREASED EXPRESSION AB Classically naive CD4(+) have been thought to differentiate into two possible lineages, T helper 1 (Th1) or T helper 2 (Th2) cells. Within this paradigm the pathogenesis of autoimmunity was suggested to predominantly relate to Th1 cells and the production of IFN-gamma. However, there were many aspects of this model that did not seem to fit, not the least of which was that IFN-gamma was protective in some models of autoimmunity. During the past 2 years, remarkable progress has been made to characterize a new lineage of helper T cells. Designated Th17 cells, this lineage selectively produces proinflammatory cytokines including IL-17, IL-21, and IL-22. In the mouse, the differentiation of this new lineage is initiated by TGF beta-1 and IL-6 and IL-21, which activate Stat3 and induce the expression of the transcription factor retinoic acid-related orphan receptor (ROR gamma t). IL-23, which also activates Stat3, apparently serves to maintain Th17 cells in vivo. In human cells, IL-1, IL-6, and IL-23 promote human Th17 differentiation, but TGF beta-1 is reportedly not needed. Emerging data have suggested that Th17 plays an essential role in the host defense against extracellular bacteria and fungi and in pathogenesis of autoimmune diseases. Selectively targeting the Th17 lineage may be beneficial for the treatment of inflammatory and autoimmune diseases. C1 [Chen, Zhi; O'Shea, John J.] Univ Turku, Inst Biomed, Fac Med, Washington, DC 20520 USA. [Chen, Zhi; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NHGRI, NIH, Bethesda, MD USA. RP Chen, Z (reprint author), Univ Turku, Inst Biomed, Fac Med, Kiinamyllynkatu 10, Washington, DC 20520 USA. EM zchen@utu.fi; osheajo@mail.nih.gov NR 110 TC 159 Z9 176 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD JUN PY 2008 VL 41 IS 2 BP 87 EP 102 DI 10.1007/s12026-007-8014-9 PG 16 WC Immunology SC Immunology GA 334TP UT WOS:000258244400001 PM 18172584 ER PT J AU Ettinger, R Kuchen, S Lipsky, PE AF Ettinger, Rachel Kuchen, Stefan Lipsky, Peter E. TI The role of IL-21 in regulating B-cell function in health and disease SO IMMUNOLOGICAL REVIEWS LA English DT Review DE IL-21; cytokines; human; autoimmunity; B cells; humoral immunity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; GROWTH-FACTOR-BETA; HELPER T-CELLS; SECRETING PLASMA-CELLS; STIMULATORY FACTOR-I; RHEUMATOID-ARTHRITIS; IGE PRODUCTION; INTERLEUKIN-21 RECEPTOR; IMMUNE-RESPONSES AB Interleukin-21 (IL-21) belongs to a family of cytokines that includes IL-2, IL-4, IL-7, IL-9, and IL-15, all of which bind to private (or shared) receptors as well as the common cytokine receptor gamma-chain as a component. Most cytokines in this family are critically important for both the maintenance and function of T cells and B cells. The receptor for IL-21 is widely distributed on lymphohematopoietic cells, and IL-21 plays many biologic roles, including maintenance and function of CD8(+) memory T cells and natural killer cells, as well as promoting the generation of Th17 cells in the mouse. One principal non-redundant role of IL-21 is the promotion of B-cell activation, differentiation or death during humoral immune responses. Furthermore, increased IL-21 production is characteristic of certain autoimmune diseases and is likely to contribute to autoantibody production as well as pathologic features of autoimmune disease. In contrast, IL-21 may function as a co-adjuvant to enhance antibody responses and thereby facilitate host defense to malignances and infectious diseases. The critical role of IL-21 in promoting humoral immune responses makes it an important focus of potential therapeutic interventions in conditions characterized by either overproduction of pathogenic autoantibodies or under production of protective antibodies. C1 [Ettinger, Rachel; Kuchen, Stefan; Lipsky, Peter E.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Ettinger, R (reprint author), Medimmune Inc, Resp Inflammat & Autoimmun Dis, 1 Medimmune Way, Gaithersburg, MD 20878 USA. EM ettingerc@medimmune.com FU Intramural NIH HHS NR 155 TC 118 Z9 124 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2008 VL 223 BP 60 EP 86 DI 10.1111/j.1600-065X.2008.00631.x PG 27 WC Immunology SC Immunology GA 325CG UT WOS:000257565200005 PM 18613830 ER PT J AU Pesu, M Laurence, A Kishore, N Zwillich, SH Chan, G O'Shea, JJ AF Pesu, Marko Laurence, Arian Kishore, Nandini Zwillich, Samuel H. Chan, Gary O'Shea, John J. TI Therapeutic targeting of Janus kinases SO IMMUNOLOGICAL REVIEWS LA English DT Review DE cytokines; immunoregulation; immunosuppression; autoimmunity; transplantation; kinase ID MICE LACKING JAK3; SEVERE COMBINED IMMUNODEFICIENCY; PROTEIN-TYROSINE KINASES; DEFECTIVE LYMPHOID DEVELOPMENT; TRANSDUCING ADAPTER MOLECULE; CHRONIC MYELOID-LEUKEMIA; T-CELL DIFFERENTIATION; RECEPTOR-GAMMA CHAIN; MYELOPROLIFERATIVE-DISORDERS; POLYCYTHEMIA-VERA AB Cytokines play pivotal roles in immunity and inflammation, and targeting cytokines and their receptors is an effective means of treating such disorders. Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. These structurally unique protein kinases play essential and specific roles in immune cell development and function. One JAK, JAK3, has particularly selective functions. Mutations of this kinase underlie severe combined immunodeficiency, indicative of its critical role in the development and function of lymphocytes. Because JAK3 appears not to have functions outside of hematopoietic cells, this kinase has been viewed as an excellent therapeutic target for the development of a new class of immunosuppressive drugs. In fact, several companies are developing JAK3 inhibitors, and Phase II studies are underway. Mutations of Tyk2 cause autosomal recessive hyperIgE syndrome, and in principle, Tyk2 inhibitors might also be useful as immunosuppressive drugs. JAK2 gain-of-function mutations (V617F) underlie a subset of disorders collectively referred to as myeloproliferative diseases and phase 2 trials using JAK inhibitors are underway in this setting. Thus, we are learning a great deal about the feasibility and effectiveness of targeting Janus kinases, and it appears likely that this will be a fruitful strategy in a variety of settings. C1 [Pesu, Marko; Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Kishore, Nandini] Pfizer, St Louis, MO USA. [Zwillich, Samuel H.; Chan, Gary] Pfizer, New London, CT USA. RP O'Shea, JJ (reprint author), Bldg 10 Magnuson CC,6N204 10 Ctr Dr,Mail Stop 161, Bethesda, MD USA. EM osheajo@mail.nih.gov RI Laurence, Arian/A-8770-2009; Pesu, marko/L-6344-2013 OI Laurence, Arian/0000-0003-0942-8292; FU Intramural NIH HHS [Z99 AR999999] NR 105 TC 131 Z9 134 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2008 VL 223 BP 132 EP 142 DI 10.1111/j.1600-065X.2008.00644.x PG 11 WC Immunology SC Immunology GA 325CG UT WOS:000257565200008 PM 18613833 ER PT J AU Carlson, JH Whitmire, WM Crane, DD Wicke, L Virtaneva, K Sturdevant, DE Kupko, JJ Porcella, SF Martinez-Orengo, N Heinzen, RA Kari, L Caldwell, HD AF Carlson, John H. Whitmire, William M. Crane, Deborah D. Wicke, Luke Virtaneva, Kimmo Sturdevant, Daniel E. Kupko, John J., III Porcella, Stephen F. Martinez-Orengo, Neysha Heinzen, Robert A. Kari, Laszlo Caldwell, Harlan D. TI The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor SO INFECTION AND IMMUNITY LA English DT Article ID GENOME SEQUENCE; COMMON PLASMID; LYMPHOGRANULOMA-VENEREUM; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; BIOVAR TRACHOMA; C-TRACHOMATIS; HOST-CELLS; GLYCOGEN; IDENTIFICATION AB Chlamydia trachomatis possesses a cryptic 7.5-kb plasmid of unknown function. Here, we describe a comprehensive molecular and biological characterization of the naturally occurring plasmidless human C trachomatis strain L2(25667R). We found that despite minimal chromosomal polymorphisms, the LGV strain L2(25667R) was indistinguishable from plasmid-positive strain L2(434) with regard to its in vitro infectivity characteristics such as growth kinetics, plaquing efficiency, and plaque size. The only in vitro phenotypic differences between L2(434) and L2(25667R) were the accumulation of glycogen granules in the inclusion matrix and the lack of the typical intrainclusion Brownian-like movement characteristic of C trachomatis strains. Conversely, we observed a marked difference between the two strains in their abilities to colonize and infect the female mouse genital tract. The 50% infective dose of plasmidless strain L2(25667R) was 400-fold greater (4 x 10(6) inclusion-forming units [IFU]) than that of plasmid-bearing strain L2(434) (1 x 10(4) IFU). Transcriptome analysis of the two strains demonstrated a decrease in the transcript levels of a subset of chromosomal genes for strain L2(25667R). Among those genes was glgA, encoding glycogen synthase, a finding consistent with the failure of L2(25667R) to accumulate glycogen granules. These findings support a primary role for the plasmid in in vivo infectivity and suggest that virulence is controlled, at least in part, by the plasmid's ability to regulate the expression of chromosomal genes. Our findings have important implications in understanding a role for the plasmid in the pathogenesis of human infection and disease. C1 [Carlson, John H.; Whitmire, William M.; Crane, Deborah D.; Heinzen, Robert A.; Kari, Laszlo; Caldwell, Harlan D.] NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Wicke, Luke; Virtaneva, Kimmo; Sturdevant, Daniel E.; Kupko, John J., III; Porcella, Stephen F.; Martinez-Orengo, Neysha] NIAID, Genom Unit Res Technol Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov FU Intramural NIH HHS NR 61 TC 94 Z9 103 U1 1 U2 9 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 JUN PY 2008 VL 76 IS 6 BP 2273 EP 2283 DI 10.1128/IAI.00102-08 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 304SH UT WOS:000256128900002 PM 18347045 ER PT J AU Via, LE Lin, L Ray, SM Carrillo, J Allen, SS Eum, SY Taylor, K Klein, E Manjunatha, U Gonzales, J Lee, EG Park, SK Raleigh, JA Cho, SN McMurray, DN Flynn, JL Barry, CE AF Via, Laura E. Lin, Ling Ray, Sonja M. Carrillo, Jose Allen, Shannon Sedberry Eum, Seok Yong Taylor, Kimberly Klein, Edwin Manjunatha, Ujjini Gonzales, Jacqueline Lee, Eun Gae Park, Seung Kyu Raleigh, James A. Cho, Sang Nae McMurray, David N. Flynn, JoAnne L. Barry, Clifton E., III TI Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates SO INFECTION AND IMMUNITY LA English DT Article ID TREATED PULMONARY LESION; SQUAMOUS-CELL CARCINOMAS; VIABLE TUBERCLE BACILLI; MYCOBACTERIUM-TUBERCULOSIS; MURINE TUBERCULOSIS; OXYGEN-TENSION; NONREPLICATING PERSISTENCE; ACQUIRED RESISTANCE; CONTAINING REGIMENS; STATIONARY-PHASE AB Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes to shorten drug regimens. Pimonidazole hydrochloride (Hypoxyprobe) is an imaging agent that is bioreductively activated only under hypoxic conditions in mammalian tissue. We employed this probe to evaluate the oxygen tension in tuberculous granulomas in four animal models of disease: mouse, guinea pig, rabbit, and nonhuman primate. Following infusion of pimonidazole into animals with established infections, lung tissues from the guinea pig, rabbit, and nonhuman primate showed discrete areas of pimonidazole adduct formation surrounding necrotic and caseous regions of pulmonary granulomas by immunohistochemical staining. This labeling could be substantially reduced by housing the animal under an atmosphere of 95% O-2. Direct measurement of tissue oxygen partial pressure by surgical insertion of a fiber optic oxygen probe into granulomas in the lungs of living infected rabbits demonstrated that even small (3-mm) pulmonary lesions were severely hypoxic (1.6 +/- 0.7 mm Hg). Finally, metronidazole, which has potent bactericidal activity in vitro only under low-oxygen culture conditions, was highly effective at reducing total-lung bacterial burdens in infected rabbits. Thus, three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis. C1 [Via, Laura E.; Ray, Sonja M.; Carrillo, Jose; Manjunatha, Ujjini; Gonzales, Jacqueline; Lee, Eun Gae; Barry, Clifton E., III] NIAID, Tuberculosis Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20852 USA. [Taylor, Kimberly] NIAID, Comparat Med Branch, NIH, Rockville, MD USA. [Lin, Ling] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA USA. [Lin, Ling; Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. [Klein, Edwin] Univ Pittsburgh, Sch Med, Div Lab Anim Resources, Pittsburgh, PA USA. [Allen, Shannon Sedberry; McMurray, David N.] Texas A&M Univ, Coll Med, Hlth Sci Ctr, College Stn, TX 77843 USA. [Eum, Seok Yong; Park, Seung Kyu] Int TB Res Ctr, Masan, South Korea. [Park, Seung Kyu] Minist Hlth & Welfare, Natl Masan TB Hosp, Masan, South Korea. [Cho, Sang Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. [Raleigh, James A.] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27514 USA. RP Barry, CE (reprint author), NIAID, Tuberculosis Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20852 USA. EM cbarry@mail.nih.gov RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU Intramural NIH HHS [Z01 AI000734-12]; NHLBI NIH HHS [R01 HL075845, HL75845]; NIAID NIH HHS [K08 AI063101, KO8 AI63101, R01 AI015495, R01 AI15495, R01 AI37895] NR 47 TC 301 Z9 304 U1 2 U2 23 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2008 VL 76 IS 6 BP 2333 EP 2340 DI 10.1128/IAI.01515-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 304SH UT WOS:000256128900008 PM 18347040 ER PT J AU Tilly, K Rosa, PA Stewart, PE AF Tilly, Kit Rosa, Patricia A. Stewart, Philip E. TI Biology of infection with Borrelia burgdorferi SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID LYME-DISEASE SPIROCHETE; OUTER-SURFACE PROTEIN; WHITE-FOOTED MICE; FIBRONECTIN-BINDING PROTEIN; IXODES-SCAPULARIS TICKS; REGULATOR FACTOR-H; GENE-EXPRESSION; SENSU-STRICTO; MAMMALIAN HOST; VISCOUS ENVIRONMENTS AB The spirochete Borrelia burgdorferi is a tick-borne obligate parasite whose normal reservoir is a variety of small mammals [1]. Although infection of these natural hosts does not lead to disease, infection of humans can result in Lyme disease as a consequence of the human immunopathologic response to B burgdoferi [2,3]. Consistent with the pathogenesis of Lyme disease, bacterial products that allow B burgdorferi to replicate and survive, rather than true "virulence factors," seem to be primarily what is required for the bacterium to cause disease in a susceptible host. In support of this idea, the genome sequence of 1331, the type strain of B burgdorferi sensu stricto [4,5], revealed that the bacterium lacks factors common to many bacterial pathogens, such as lipopolysaccharide, toxins, and specialized secretion systems. In this article, the authors describe the basic biology of B burgdorferi and review some of the bacterial components required for infection of and survival in the mammalian and tick hosts. C1 [Tilly, Kit; Rosa, Patricia A.; Stewart, Philip E.] NIAID, Rocky Mt Labs, NIH, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. RP Stewart, PE (reprint author), NIAID, Rocky Mt Labs, NIH, Lab Zoonot Pathogens, 903 S 4th St, Hamilton, MT 59840 USA. EM pestewart@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 173 TC 67 Z9 73 U1 1 U2 35 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2008 VL 22 IS 2 BP 217 EP + DI 10.1016/j.idc.2007.12.013 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305KD UT WOS:000256176400004 PM 18452798 ER PT J AU Marques, A AF Marques, Adriana TI Chronic Lyme disease: A review SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SOLITARY ERYTHEMA MIGRANS; BORRELIA-BURGDORFERI; ANTIBIOTIC-TREATMENT; CEFUROXIME AXETIL; FOLLOW-UP; DOUBLE-BLIND; PERSISTENT SYMPTOMS; CONTROLLED TRIAL; REFERRAL CENTER; CHILDREN AB Studies have shown that most patients diagnosed with chronic Lyme disease either have no objective evidence of previous or current infection with Borrelia burgdorferi or are patients who should be classified as having post-Lyme disease syndrome, which is defined as continuing or relapsing nonspecific symptoms (such as fatigue, musculoskeletal pain, and cognitive complaints) in a patient previously treated for Lyme disease. Despite extensive study, there is currently no clear evidence that post-Lyme disease syndrome is caused by persistent infection with B burgdorferi. Four randomized placebo-controlled studies have shown that antibiotic therapy offers no sustained benefit to patients who have post-Lyme disease syndrome. These studies also showed a substantial placebo effect and a significant risk of treatment-related adverse events. Further research to elucidate the mechanisms underlying persistent symptoms after Lyme disease and controlled trials of new approaches to the treatment and management of these patients are needed. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Marques, A (reprint author), NIAID, Lab Clin Infect Dis, NIH, 10-11N234 10 Ctr Dr, Bethesda, MD 20892 USA. EM amarques@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000695-12, Z99 AI999999] NR 79 TC 67 Z9 72 U1 8 U2 26 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2008 VL 22 IS 2 BP 341 EP + DI 10.1016/j.idc.2007.12.011 PG 22 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305KD UT WOS:000256176400012 PM 18452806 ER PT J AU Blood-Siegfried, J Rambaud, C Nyska, A Germolec, DR AF Blood-Siegfried, Jane Rambaud, Caroline Nyska, Abraham Germolec, Dori R. TI Evidence for infection, inflammation and shock in sudden infant death: parallels between a neonatal rat model of sudden death and infants who died of sudden infant death syndrome SO INNATE IMMUNITY LA English DT Article DE endotoxin; organ shock; sudden infant death syndrome; SIDS; thymic involution ID INFLUENZA-A VIRUS; SYNDROME SIDS; CHILDHOOD; APOPTOSIS; ENDOTOXIN; THYMUS; RISK; PUPS AB This study compared pathological findings from a neonatal rat model of sudden death with those from 40 sudden infant death syndrome (SIDS) infants collected at autopsy. In the rat model, influenza A virus was administered intranasally on postnatal day 10, and on day 12 a sublethal, intraperitoneal dose of Escherichia coli endotoxin; mortality was 80%. Tissue samples from the animals and infants were fixed in formaldehyde, embedded in paraffin, and sections stained with hematoxylin and eosin. Tissues from the SIDS specimens were additionally cultured for bacteria and viruses; post-mortem blood samples were evaluated for signs of inflammation. All sections were examined by a pediatric forensic pathologist familiar with SIDS pathology. Comparisons between the rat model and the human SIDS cases revealed that both exhibited gross and microscopic pathology related to organ shock, possibly associated with the presence of endotoxin. Uncompensated shock appeared to be a likely factor that caused death in both infants and rat pups. Response to a shock-inducing event might have played an important role in the events leading to death. The similarities between the neonatal rats and the human cases indicate that further research with the model might elucidate additional aspects of SIDS pathology. C1 [Blood-Siegfried, Jane] Duke Univ, Med Ctr, Durham, NC 27707 USA. [Rambaud, Caroline] Hop Raymond Poincare, Serv Med Legale, Garches, France. [Blood-Siegfried, Jane; Nyska, Abraham; Germolec, Dori R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Blood-Siegfried, J (reprint author), Duke Univ, Med Ctr, Box 3322, Durham, NC 27707 USA. EM blood002@mc.duke.edu OI Blood-Siegfried, Jane/0000-0003-1926-9758 FU Intramural NIH HHS [Z99 ES999999] NR 32 TC 11 Z9 11 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-4259 J9 INNATE IMMUN JI Innate Immun. PD JUN PY 2008 VL 14 IS 3 BP 145 EP 152 DI 10.1177/1753425908090730 PG 8 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 328ST UT WOS:000257818800002 PM 18562573 ER PT J AU Krinsky-McHale, SJ Devenny, DA Gu, H Jenkins, EC Kittler, P Murty, VV Schupf, N Scotto, L Tycko, B Urv, TK Ye, L Zigman, WB Silverman, W AF Krinsky-McHale, Sharon J. Devenny, Darlynne A. Gu, Hong Jenkins, Edmund C. Kittler, Phyllis Murty, Vundavalli V. Schupf, Nicole Scotto, Luigi Tycko, Benjamin Urv, Tiina K. Ye, Lingling Zigman, Warren B. Silverman, Wayne TI Successful aging in a 70-year-old man with Down syndrome: A case study SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article ID HUMAN GENE-EXPRESSION; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; MENTAL-RETARDATION; LIFE EXPECTANCY; NEUROPATHOLOGICAL CHANGES; ADAPTIVE-BEHAVIOR; OLD-AGE; ADULTS; DEMENTIA AB The authors present a case study of a 70-year-old man with Down syndrome ("Mr. C.") who they followed for 16 years and who does not exhibit declines in cognitive or functional capacities indicative of dementia, despite having well-documented, complete trisomy 21. The authors describe the age-associated changes that occurred over 16 years as well as provide detailed information regarding Mr. C.'s health and genetic status. To further emphasize Mr. C.'s successful aging, the authors compared his longitudinal performance profile with that of 2 peers of comparable level of intellectual functioning: I similar-aged man with clinical Alzheimer's disease and a younger man who was healthy. The authors present potential explanations for the phenotypic variability observed in individuals with Down syndrome. C1 [Krinsky-McHale, Sharon J.; Schupf, Nicole] Columbia Univ, Med Ctr, New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. [Murty, Vundavalli V.; Schupf, Nicole; Scotto, Luigi] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA. [Schupf, Nicole] Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Tycko, Benjamin] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10027 USA. [Urv, Tiina K.] NICHHD, Bethesda, MD 20892 USA. [Silverman, Wayne] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Silverman, Wayne] Kennedy Krieger Inst, Baltimore, MD 21205 USA. RP Krinsky-McHale, SJ (reprint author), Columbia Univ, Med Ctr, New York State Inst Basic Res Dev Disabil, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM Sharon.Krinsky-McHale@omr.state.ny.us FU NIA NIH HHS [R01 AG 14771]; NICHD NIH HHS [P01 HD 35897, P01 HD035897] NR 94 TC 11 Z9 11 U1 0 U2 3 PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES PI WASHINGTON PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA SN 1934-9491 J9 INTELLECT DEV DISAB JI Intellect. Dev. Disabil. PD JUN PY 2008 VL 46 IS 3 BP 215 EP 228 DI 10.1352/2008.46:215-228 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 327ZJ UT WOS:000257766700005 PM 18578579 ER PT J AU Berra, L Curto, F Bassi, GL Laquerriere, P Pitts, B Baccarelli, A Kolobow, T AF Berra, Lorenzo Curto, Francesco Bassi, Gianluigi Li Laquerriere, Patrice Pitts, Betsey Baccarelli, Andrea Kolobow, Theodor TI Antimicrobial-coated endotracheal tubes: an experimental study SO INTENSIVE CARE MEDICINE LA English DT Article DE endotracheal tube; mechanical ventilation; bacterial biofilm; ventilator-associated pneumonia; silver sulfadiazine ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE UNITS; BACTERIAL-COLONIZATION; URINARY CATHETERS; HOSPITALIZED-PATIENTS; INFECTION; BIOFILM; PREVENTION; RESISTANCE; ADHESION AB Objective: Antibiotic-resistant bacterial biofilm may quickly form on endotracheal tubes ( ETTs) and can enter the lungs, potentially causing pneumonia. In an attempt to prevent bacterial colonization, we developed and tested in an in-vitro study and animal study several antibacterial-coated ETTs ( silver sulfadiazine with and without carbon in polyurethane, silver sulfadiazine and chlorhexidine with and without carbon in polyurethane, silver-platinum with and without carbon in polyurethane, in polyurethane, and rose bengal for UV light). Design, setting, animals, interventions: After preliminary silver sulfadiazine in ( SSD-ETT) was selected among the coatings to be challenged every 24 h with 10(4)-10(6) Pseudomonas aeruginosa/ml and evaluated at 6 h, 24 h, and 72 h with standard microbiological studies, scanning electron microscopy, and confocal scanning microscopy. Subsequently, eight sheep were randomized to receive either a SSD-ETT or a standard ETT ( St-ETT). After 24 h of mechanical ventilation, standard microbiological studies were performed together with scanning electron microscopy and confocal microscopy. Measurements and results: In the in-vitro study SSD-ETT remained bacteria-free for up to 72 h, whereas St-ETT showed heavy P. aeruginosa growth and biofilm formation ( p < 0.01). In sheep, the SSD-ETT group showed no bacterial growth in the ETT, ventilator tubing, and lower respiratory tract, while heavy colonization was found in the St-ETT ( p < 0.01), ventilator tubing ( p = 0.03), and lower respiratory tract ( p < 0.01). Conclusion: This study describes several effective and durable antibacterial coatings for ETTs. Particularly, SSD-ETT showed prevention against P. aeruginosa biofilm formation in a 72-h in-vitro study and lower respiratory tract colonization in sheep mechanically ventilated for 24 h. C1 [Berra, Lorenzo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Curto, Francesco; Bassi, Gianluigi Li; Kolobow, Theodor] NHLBI, NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. [Laquerriere, Patrice] Univ Reims, INSERM, ERM 0203, Lab Microscopie Elect,UFR Sci, F-51685 Reims, France. [Pitts, Betsey] Montana State Univ, Ctr Biofilm Engn, Bozeman, MT 59717 USA. [Pitts, Betsey] Montana State Univ, Dept Chem Engn, Bozeman, MT 59717 USA. [Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,Boston WHT-4-436, Boston, MA 02215 USA. EM lberra@partners.org RI Laquerriere, Patrice/P-1025-2016; OI Laquerriere, Patrice/0000-0001-7637-9094; Baccarelli, Andrea/0000-0002-3436-0640 NR 31 TC 29 Z9 35 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2008 VL 34 IS 6 BP 1020 EP 1029 DI 10.1007/s00134-008-1099-3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 319QZ UT WOS:000257180100008 PM 18418572 ER PT J AU Berra, L Kolobow, T Laquerriere, P Pitts, B Bramati, S Pohlmann, J Marelli, C Panzeri, M Brambillasca, P Villa, F Baccarelli, A Bouthors, S Stelfox, HT Bigatello, LM Moss, J Pesenti, A AF Berra, Lorenzo Kolobow, Theodor Laquerriere, Patrice Pitts, Betsey Bramati, Simone Pohlmann, Joshua Marelli, Chiara Panzeri, Miriam Brambillasca, Pietro Villa, Federico Baccarelli, Andrea Bouthors, Sylvie Stelfox, Henry T. Bigatello, Luca M. Moss, Joel Pesenti, Antonio TI Internally coated endotracheal tubes with silver sulfadiazine in polyurethane to prevent bacterial colonization: a clinical trial SO INTENSIVE CARE MEDICINE LA English DT Article DE endotracheal tube; mechanical ventilation; bacterial biofilm; ventilator-associated pneumonia; silver sulfadiazine ID VENTILATOR-ASSOCIATED PNEUMONIA; NOSOCOMIAL INFECTIONS; LEUKOPENIA SECONDARY; TRACHEAL TUBE; BIOFILM; THERAPY; PATIENT; ARGYRIA; CREAM AB Objective: Coated medical devices have been shown to reduce catheter-related infections. We coated endotracheal tubes ( ETT) with silver sulfadiazine ( SSD), and tested them in a clinical study to assess the feasibility, safety, and efficacy of preventing bacterial colonization. Design: A prospective, randomized clinical trial, phase I-II. Setting: Academic intensive care unit ( ICU). Participants: Forty-six adult patients expected to need 12-24 h of intubation were randomized into two groups. Interventions: Patients were randomized to be intubated with a standard non-coated ETT ( St-ETT, n = 23; control group), or with a SSD-coated ETT ( SSD-ETT, n = 23). Measurements and results: Coating with SSD prevented bacterial colonization of the ETT ( frequency of colonization: SSD-ETT 0/23, St-ETT 8/23; p < 0.01). No organized bacterial biofilm could be identified on the lumen of any ETT; however, SSD was associated with a thinner mucus layer ( in the SSD-ETT secretion deposits ranged from 0 to 200 mu m; in the St-ETT deposits ranged between 50 and 700 mu m). No difference was observed between the two groups in the tracheobronchial brush samples ( frequency of colonization: SSD-ETT 0/23, St-ETT 2/23; p = 0.48). No adverse reactions were observed with the implementation of the novel device. Conclusion: SSD-ETT can be safely used in preventing bacterial colonization and narrowing of the ETT in patients intubated for up to 24 h ( mean intubation time 16 h). C1 [Berra, Lorenzo; Villa, Federico; Stelfox, Henry T.; Bigatello, Luca M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kolobow, Theodor; Baccarelli, Andrea; Moss, Joel] NHLBI, NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. [Laquerriere, Patrice; Bouthors, Sylvie] Univ Reims, INSERM, ERM 0203, UFR Sci,Lab Microscopie Elect, F-51685 Reims, France. [Pitts, Betsey] Montana State Univ, Ctr Biofilm Engn, Bozeman, MT 59717 USA. [Pitts, Betsey] Montana State Univ, Dept Chem Engn, Bozeman, MT 59717 USA. [Bramati, Simone; Pohlmann, Joshua; Marelli, Chiara; Panzeri, Miriam; Brambillasca, Pietro; Pesenti, Antonio] Milano Bicocca Univ, San Gerardo Hosp, I-20052 Monza Milan, Italy. RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM lberra@partners.org RI Pesenti, Antonio/H-7483-2012; Laquerriere, Patrice/P-1025-2016; OI Laquerriere, Patrice/0000-0001-7637-9094; Baccarelli, Andrea/0000-0002-3436-0640 NR 40 TC 36 Z9 45 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2008 VL 34 IS 6 BP 1030 EP 1037 DI 10.1007/s00134-008-1100-1 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 319QZ UT WOS:000257180100009 PM 18418571 ER PT J AU Zanella, A Cressoni, M Epp, M Stylianou, M Kolobow, T AF Zanella, Alberto Cressoni, Massimo Epp, Myra Stylianou, Mario Kolobow, Theodor TI A double-layer tracheal tube cuff designed to prevent leakage: a bench-top study SO INTENSIVE CARE MEDICINE LA English DT Article DE tube, endotracheal; cuff; leakage, fluid; aspiration; ventilator-associated pneumonia ID LOW-PRESSURE; ASPIRATION; PNEUMONIA; VOLUME; LATEX AB Objective: We designed a new endotracheal tube (ETT) cuff that does not form the folds that cause leakage of colonized subglottic secretions upon inflation within the trachea: a standard high-volume low-pressure cuff was draped with a second, highly elastic cuff made of a low-protein guayule natural latex rubber with 0.5 ml gel between the cuffs. We compared this prototype ETT cuff with four commercially available ETTs for efficacy in the prevention of fluid leakage across the cuff. Design: In vitro study. Measurements and results: We compared fluid leakage in our prototype cuff with that in four commercially available ETTs. Three cylindrical glass tubes 16, 20, and 22 mm in diameter were used as model tracheas, and five different intracuff pressures ( 20, 25, 30, 40, and 50 cmH(2)O) were tested. Each test was repeated three times with new ETTs. The guayule latex ETT cuff showed an average fluid leakage of 0.0007 +/- 0.002 ml/min which was significantly lower than that in any of the other ETTs ( Microcuff 0.07 +/- 0.09, Mallinckrodt/Hi-Lo Evac 5 +/- 5, Euromedical 7 +/- 4, Sheridan/CF 41 +/- 69). Conclusions: Our prototype ETT cuff significantly reduced fluid leakage in this bench-top study. In vivo testing and evaluation is to follow. C1 [Zanella, Alberto; Cressoni, Massimo; Epp, Myra; Kolobow, Theodor] NHLBI, NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. [Stylianou, Mario] NHLBI, NIH, Off Biostat Res, OD, Bethesda, MD 20892 USA. RP Zanella, A (reprint author), NHLBI, NIH, Pulm & Crit Care Med Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM zanella.alb@gmail.com RI Cressoni, Massimo/B-7315-2017; OI Cressoni, Massimo/0000-0002-0089-2905; zanella, Alberto/0000-0002-2967-2527 NR 16 TC 22 Z9 23 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2008 VL 34 IS 6 BP 1145 EP 1149 DI 10.1007/s00134-008-1016-9 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 319QZ UT WOS:000257180100025 PM 18259729 ER PT J AU Piao, S Ryu, JK Shin, HY Zhang, L Song, SU Han, JY Park, SH Kim, JM Kim, IH Kim, SJ Suh, JK AF Piao, Shuguang Ryu, Ji-Kan Shin, Hwa-Yean Zhang, Luwei Song, Sun U. Han, Jee-Young Park, Seok Hee Kim, Joon Mee Kim, In-Hoo Kim, Seong-Jin Suh, Jun-Kyu TI Repeated intratunical injection of adenovirus expressing transforming growth factor-beta 1 in a rat induces penile curvature with tunical fibrotic plaque: a useful model for the study of Peyronie's disease SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article DE animal model; penile curvature; Peyronie's disease; transforming growth factor-beta ID PROTEIN EXPRESSION; ANIMAL-MODEL; NITRIC-OXIDE; INCREASE; PREVALENCE; FIBRIN; TRAUMA AB This study was undertaken to establish a Peyronie's disease model with penile curvature by using recombinant transforming growth factor-beta 1 (TGF-beta 1) protein or adenovirus (ad-TGF-beta 1). Four-month-old male Sprague-Dawley rats were divided into seven groups (n = 18 per group): G1 received a single injection of saline into the tunica albuginea (0.1 mL); G2, repeated injections of ad-LacZ (days 0, 3, and 6; 1 x 10(10) particles/0.1 mL respectively); G3, a single injection of recombinant TGF-beta 1 protein (700 ng/0.1 mL); G4, repeated injections of recombinant TGF-beta 1 protein (days 0, 3 and 6; 700 ng/0.1 mL respectively); G5, a single injection of low-dose ad-TGF-beta 1 (1 x 10(10) particles/0.1 mL); G6, a single injection of high-dose ad-TGF-beta 1 (3 x 10(10) particles/0.1 mL); and G7, repeated injections of low-dose ad-TGF-beta 1 (days 0, 3, and 6; 1 x 10(10) particles/0.1 mL respectively). Penile curvature was evaluated 30, 45 and 60 days after treatment, and the penis was then harvested for histological examination. Repeated injection of low-dose ad-TGF-beta 1 not only induced fibrous scar in the tunica, which lasted up to 60 days after injection, but also resulted in significant penile curvature by artificial erection test 45 days after treatment. A peculiar histological finding in this group was trapping of inflammatory cells in the tunica, subsequent fibrosis, and formation of cartilage and calcification as well as loss of elastin fibres. This model involving repeated injection of ad-TGF-beta 1 may contribute to further investigation of the pathogenesis of Peyronie's disease and the development of new therapeutics targeting this pathway. C1 [Piao, Shuguang; Ryu, Ji-Kan; Shin, Hwa-Yean; Zhang, Luwei; Suh, Jun-Kyu] Inha Univ Hosp, Dept Urol, Sch Med, Inchon 400711, South Korea. [Song, Sun U.] Inha Univ, Sch Med, Clin Res Ctr, Inchon 400711, South Korea. [Han, Jee-Young; Park, Seok Hee; Kim, Joon Mee] Inha Univ, Sch Med, Dept Pathol, Inchon, South Korea. [Kim, In-Hoo] Natl Canc Ctr, Res Inst, Goyang, Gyeonggi, South Korea. [Kim, Seong-Jin] NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Suh, JK (reprint author), Inha Univ Hosp, Dept Urol, Sch Med, 7-206 3rd St, Inchon 400711, South Korea. EM jksuh@inha.ac.kr NR 17 TC 13 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD JUN PY 2008 VL 31 IS 3 BP 346 EP 353 DI 10.1111/j.1365-2605.2007.00780.x PG 8 WC Andrology SC Endocrinology & Metabolism GA 296NB UT WOS:000255552000007 PM 17651407 ER PT J AU Guech-Ongey, M Engels, EA Goedert, JJ Biggar, RJ Mbulaiteye, SM AF Guech-Ongey, Mercy Engels, Eric A. Goedert, James J. Biggar, Robert J. Mbulaiteye, Sam M. TI Elevated risk for squamous cell carcinoma of the conjunctiva among adults with AIDS in the United States SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ocular cancer; squamous cell carcinoma of conjunctiva; lymphoma; ultraviolet radiation; HIV/AIDS ID IMMUNODEFICIENCY-VIRUS-INFECTION; EPIDEMIOLOGY; CANCERS; HIV; UGANDA; IMMUNOSUPPRESSION; NEOPLASIA; SPECTRUM; AFRICA; EYE AB Squamous cell carcinoma of the conjunctiva (SCCC) has been associated with HIV infection in equatorial Africa, but the evidence for association with HIV in developed countries, where SCCC is rarer, is controversial. We investigated the risk for SCCC and other eye cancers in the updated U.S. HIV/AIDS Cancer Match Registry Study. We calculated standardized incidence ratios (SIRs) to estimate excess risk for SCCC, primary ocular lymphoma, ocular Kaposi sarcoma (KS) and other eye tumors among 491, 048 adults (aged > 15 years or older) with HIV/AIDS diagnosed from 1980 to 2004. We calculated relative proportions (per 105) to gain insight into risk factors. We identified 73 eye cancers (15 SCCC, 35 primary ocular lymphoma, 17 ocular KS and 6 other). Overall SIRs were elevated for SCCC (SIR, 12.2, 95% CI 6.8-20.2), primary ocular lymphoma (21.7, 95% CI 15.1-30.2) and ocular KS (109, 95% CI 63.5-175). Risk for SCCC was elevate regardless of HIV acquisition category, CD4 lymphocyte count and time relative to AIDS-onset. Relative proportions of SCCC risk were highest with age >= 50 (8/10(5)), Hispanic ethnicity (7/10(5)) and residence in regions with high-solar ultraviolet radiation (10/ 10(5)). We show significantly increased incidence of SCCC among persons with HIV/AIDS in the U.S. The associations with age and geography are in accord with etiological role for ultraviolet radiation in SCCC. (C) 2008 Wilcy-Liss, Inc. C1 [Guech-Ongey, Mercy; Engels, Eric A.; Goedert, James J.; Biggar, Robert J.; Mbulaiteye, Sam M.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Biggar, Robert J.] State Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. RP Guech-Ongey, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Execut Plaza S,Rm 7078, Rockville, MD 20852 USA. EM guechome@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N02-CP-31003] NR 22 TC 33 Z9 36 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2008 VL 122 IS 11 BP 2590 EP 2593 DI 10.1002/ijc.23384 PG 4 WC Oncology SC Oncology GA 295HT UT WOS:000255466300025 PM 18224690 ER PT J AU Cook, MB Graubard, BI Rubertone, MV Erickson, RL McGlynn, KA AF Cook, Michael B. Graubard, Barry I. Rubertone, Mark V. Erickson, Ralph L. McGlynn, Katherine A. TI Perinatal factors and the risk of testicular germ cell tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE nonseminoma; perinatal risk factors; seminoma; testicular cancer ID CARCINOMA-IN-SITU; BIRTH-WEIGHT; CANCER INCIDENCE; MALES BORN; YOUNG MEN; TESTIS; COHORT; AGE; CRYPTORCHIDISM; NONSEMINOMA AB Testicular germ cell tumors (TGCT) are the most common cancer among young men in the United States and Western Europe. Prior evidence suggests that TGCT may arise in perinatal life, although few risk factors have yet been identified. To study the etiology of TGCT, the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study enrolled participants and their mothers between 2002 and 2005. Five hundred twenty-seven mothers of cases and 561 mothers of controls provided information on perinatal variables. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95%Cl) associated with the candidate risk factors. Analyses were conducted for all TGCT together and for each histologic subgroup (seminoma and nonseminoma) separately. Young maternal age (<20 vs. 20-29 years, OR = 1.51, 95%Cl: 1.09-2.10), young paternal age (<25 vs. 25-29 years, OR = 1.45, 95%Cl: 1.08-1.94), maternal parity (3 vs. 1, OR = 0.63, 95%Cl: 0.44-0.90) and breech birth (OR = 1.92, 95%Cl: 1.03-3.56) were associated with risk of TGCT. For seminoma, young maternal age (<20 vs. 20-29 years, OR = 1.67, 95%Cl: 1.10-2.54), young paternal age (<25 vs. 25-29 years, OR = 1.53, 95 % Cl: 1.03-2.27), maternal parity (3 vs. 1, OR = 0.58, 95%Cl: 0.35-0.96) and low birth weight (<2,500 g vs. 2,500-4,000 g, OR = 1.82, 95%Cl: 1.00-3.30) were risk factors. Nonseminoma was associated with breech birth (OR = 2.44, 95%Cl: 1.25-4.78) and Cesarean section (OR = 2.10, 95%Cl: 1.25-3.54). These results support the hypothesis that TGCT may originate in very early life. (c) 2008 Wiley-Liss, Inc. C1 [Cook, Michael B.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, NIH, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Silver Spring, MD USA. [Erickson, Ralph L.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP Cook, MB (reprint author), NCI, NIH, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet,Dept Hlth & Human Serv, EPS-5005,6120 Execut Blvd, Bethesda, MD 20892 USA. EM cookmich@mail.nih.gov RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural NIH HHS [Z99 CA999999] NR 45 TC 37 Z9 38 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2008 VL 122 IS 11 BP 2600 EP 2606 DI 10.1002/ijc.23424 PG 7 WC Oncology SC Oncology GA 295HT UT WOS:000255466300027 PM 18324625 ER PT J AU Shah, S Kapoor, A Ding, J Guion, P Petrisor, D Karanian, J Pritchard, WF Stoianovici, D Wood, BJ Cleary, K AF Shah, S. Kapoor, A. Ding, J. Guion, P. Petrisor, D. Karanian, J. Pritchard, W. F. Stoianovici, D. Wood, B. J. Cleary, K. TI Robotically assisted needle driver: evaluation of safety release, force profiles, and needle spin in a swine abdominal model SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Robotics/instrumentation; Safety; Minimally invasive; Rotating needle driver AB Objective The objective of this study was to evaluate two features of a new rotating needle driver in a domestic swine model: (1) a quick release safety mechanism and (2) the impact of spinning the needle on the force profile. Materials and methods The experiments were conducted in a multi-modality interventional suite. An initial CT scan was obtained to determine the location of the target, in the liver or lung. The robotic arm was positioned directly over the marked skin entry point. Control parameters were set to rotation speeds of 0, 90, or 180 rpm. The breakaway force magnitude was also preset to a predetermined force. The physician used the joystick to drive the needle towards the target while the system recorded needle insertion depth and forces. Results Sixteen insertions were completed (14 in liver and 2 in lung) and 12 released the needle upon the desired set force. The mean response time of the quick release mechanism was 202 +/- 39 ms. Needle rotation resulted in reduced insertion force. Conclusion The robot-assisted needle insertion system was shown to be functional in a multimodality imaging clinical environment on a swine model. The system has potential future applications in precision minimally invasive procedures including biopsy and radiofrequency ablation. C1 [Shah, S.; Kapoor, A.; Guion, P.; Wood, B. J.] Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Ding, J.; Cleary, K.] Georgetown Univ, Dept Radiol, Imaging Sci & Informat Syst ISIS Ctr, Washington, DC USA. [Petrisor, D.; Stoianovici, D.] Johns Hopkins Med, Dept Urol, URobot Lab, Baltimore, MD USA. [Karanian, J.; Pritchard, W. F.] US FDA, Lab Cardiovasc & Intervent Therapeut, Laurel, MD USA. RP Shah, S (reprint author), Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM shahsap@cc.nih.gov; cleary@georgetown.edu FU NIH/NCI [5R33CA094274]; U.S. Army [W81XWH-04-1-007]; NIH FX Portions of this work were funded under NIH/NCI grant 5R33CA094274 and U.S. Army grant W81XWH-04-1-007, administered by the Telemedicine and Advanced Technology Research Center (TATRC), Fort Detrick, MD, USA. This research was also supported in part by the Intramural Research Program of the NIH. NR 25 TC 14 Z9 14 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2008 VL 3 IS 1-2 BP 173 EP 179 DI 10.1007/s11548-008-0164-2 PG 7 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZZ UT WOS:000208990400020 ER PT J AU Gilman, SE Martin, LT Abrams, DB Kawachi, I Kubzansky, L Loucks, EB Rende, R Rudd, R Buka, SL AF Gilman, Stephen E. Martin, Laurie T. Abrams, David B. Kawachi, Ichiro Kubzansky, Laura Loucks, Eric B. Rende, Richard Rudd, Rima Buka, Stephen L. TI Educational attainment and cigarette smoking: a causal association? SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE education; smoking; causality; disparities ID SELF-REPORTED SMOKING; TOBACCO USE; NICOTINE DEPENDENCE; UNITED-STATES; ADOLESCENT SMOKING; EUROPEAN COUNTRIES; REGRESSION-MODELS; YOUNG-ADULTS; FOLLOW-UP; BEHAVIOR AB Background Despite abundant evidence that lower education is associated with a higher risk of smoking, whether the association is causal has not been convincingly established. Methods We investigated the association between education and lifetime smoking patterns in a birth cohort established in 1959 and followed through adulthood (n 1311). We controlled for a wide range of potential confounders that were measured prior to school entry, and also estimated sibling fixed effects models to control for unmeasured familial vulnerability to smoking. Results In the full sample of participants, regression analyses adjusting for multiple childhood factors (including socioeconomic status, IQ, behavioural problems, and medical conditions) indicated that the number of pack-years smoked was higher among individuals with less than high school education [rate ratio (RR) 1.58, confidence interval (CI) 1.31, 1.91]. However, in the sibling fixed effects analysis the RR was 1.23 (CI 0.80, 1.93). Similarly, adjusted models estimated in the full sample showed that individuals with less than high school education had fewer short-term (RR 0.40; CI 0.23, 0.69) and long-term (RR 0.59; CI 0.42, 0.83) quit attempts, and were less likely to quit smoking (odds ratio 0.34; CI 0.19, 0.62). The effects of education on quitting smoking were attenuated in the sibling fixed effects models that controlled for familial vulnerability to smoking. Conclusions A substantial portion of the education differential in smoking that has been repeatedly observed is attributable to factors shared by siblings that contribute to shortened educational careers and to lifetime smoking trajectories. Reducing disparities in cigarette smoking, including educational disparities, may therefore require approaches that focus on factors early in life that influence smoking risk over the adult life span. C1 [Gilman, Stephen E.; Kawachi, Ichiro; Kubzansky, Laura; Rudd, Rima] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Martin, Laurie T.] Child Trends, Washington, DC USA. [Abrams, David B.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Loucks, Eric B.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Loucks, Eric B.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. [Rende, Richard] Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. [Rende, Richard] Butler Hosp, Providence, RI 02906 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Hungtington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Buka, Stephen/H-7335-2014; Gilman, Stephen/E-7632-2010; Loucks, Eric/I-1272-2014 OI Buka, Stephen/0000-0002-8578-9308; Gilman, Stephen/0000-0002-8331-6419; Loucks, Eric/0000-0002-9962-0386 FU NCI NIH HHS [P50 CA084719]; NIA NIH HHS [AG023397, R01 AG023397, RC2 AG036666] NR 69 TC 86 Z9 86 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2008 VL 37 IS 3 BP 615 EP 624 DI 10.1093/ije/dym250 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 310HY UT WOS:000256520700027 PM 18180240 ER PT J AU Freedman, DM AF Freedman, D. Michal TI Commentary: The complexities of minimizing risks due to UV exposures SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID VITAMIN-D C1 NCI, NIH, DHHS, Bethesda, MD 20892 USA. RP Freedman, DM (reprint author), NCI, NIH, DHHS, Bethesda, MD 20892 USA. EM freedmam@mail.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2008 VL 37 IS 3 BP 667 EP 668 DI 10.1093/ije/dyn061 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 310HY UT WOS:000256520700033 PM 18453633 ER PT J AU Truelove, AL Oleksyk, TK Shrestha, S Thio, CL Goedert, JJ Donfield, SM Kirk, GD Thomas, DL O'Brien, SJ Smith, MW AF Truelove, Ann L. Oleksyk, Taras K. Shrestha, Sadeep Thio, Chloe L. Goedert, James J. Donfield, Sharyne M. Kirk, Gregory D. Thomas, David L. O'Brien, Stephen J. Smith, Michael W. TI Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcome SO INTERNATIONAL JOURNAL OF IMMUNOGENETICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLAQUE-TYPE PSORIASIS; SINGLE NUCLEOTIDE POLYMORPHISMS; PROMOTER POLYMORPHISMS; DRUG-USERS; HEPATOCELLULAR-CARCINOMA; HIV-1 INFECTION; CYTOKINES IL-19; INTERLEUKIN-10; ASSOCIATION AB Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case-control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005-0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy-Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01-0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis. C1 [Truelove, Ann L.; Oleksyk, Taras K.; Shrestha, Sadeep; O'Brien, Stephen J.; Smith, Michael W.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Truelove, Ann L.; Oleksyk, Taras K.; Shrestha, Sadeep; Smith, Michael W.] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Thio, Chloe L.; Thomas, David L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Rockville, MD USA. [Donfield, Sharyne M.] Rho Inc, Chapel Hill, NC USA. [Kirk, Gregory D.; Thomas, David L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Smith, MW (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM smithm@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; Smith, Michael/B-5341-2012; Taras, Oleksyk/J-8805-2013 OI Taras, Oleksyk/0000-0002-8148-3918 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01 CO012400, N01-CO-12400]; NIDA NIH HHS [R01 DA013324, R01 DA013324-01, R01 DA13324] NR 54 TC 28 Z9 34 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3121 J9 INT J IMMUNOGENET JI Int. J. Immunogenet. PD JUN PY 2008 VL 35 IS 3 BP 255 EP 264 DI 10.1111/j.1744-313X.2008.00770.x PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 300KT UT WOS:000255823400011 PM 18479293 ER PT J AU Katrapkou, A Simitsopoulou, M Kruhlak, M Chatzimoschou, A Georgiadou, E Cotten, C Walsh, T Roilides, E AF Katrapkou, Aspasia Simitsopoulou, Maria Kruhlak, Michael Chatzimoschou, Athanasios Georgiadou, Elpiniki Cotten, Catherine Walsh, Thomas Roilides, Emmanuel TI Interactions between human phagocytes and newer antifungal agents against Candida albicans biofilms SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Katrapkou, Aspasia; Simitsopoulou, Maria; Kruhlak, Michael; Chatzimoschou, Athanasios; Georgiadou, Elpiniki; Cotten, Catherine; Walsh, Thomas; Roilides, Emmanuel] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Kruhlak, Michael; Cotten, Catherine; Walsh, Thomas] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 113 BP S46 EP S46 DI 10.1016/S1201-9712(08)60115-0 PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300113 ER PT J AU Kuhns, D Vinh, D Uzel, G Gallin, J Holland, S AF Kuhns, Douglas Vinh, Donald Uzel, Gulbu Gallin, John Holland, Steven TI Herniated nuclear morphology and cytoskeletal anomalies in neutrophils from sisters with recurrent infections SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Kuhns, Douglas] SAIC-Frederick Inc, Clin Serv Program, NCI, Frederick, MD USA. [Vinh, Donald; Uzel, Gulbu; Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Gallin, John] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 13 BP S6 EP S7 DI 10.1016/S1201-9712(08)60015-6 PG 2 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300013 ER PT J AU Michailidis, L Marchand, B Kodama, EI Fopoussi, AOM Sawani, A Ryan, E Eisele, N Matsuoka, M Ashida, N Nagy, E Parniak, M Mitsuya, H Sarafianos, S AF Michailidis, Lefteris Marchand, Bruno Kodama, Ei-Ichi Fopoussi, Amelie Olga Mafotsing Sawani, Ali Ryan, Emilie Eisele, Nicholas Matsuoka, Masao Ashida, Noriyuki Nagy, Eva Parniak, Michael Mitsuya, Hiroaki Sarafianos, Stefan TI Novel inhibition mechanism and potent activity of trans location-deficient reverse transcriptase inhibitors SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Michailidis, Lefteris; Marchand, Bruno; Fopoussi, Amelie Olga Mafotsing; Sawani, Ali; Ryan, Emilie; Eisele, Nicholas; Sarafianos, Stefan] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. [Kodama, Ei-Ichi; Matsuoka, Masao] Kyoto Univ, Inst Virus Res, Kyoto 606, Japan. [Ashida, Noriyuki] Yamasa Corp, Chiba, Japan. [Nagy, Eva; Parniak, Michael] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Kumamoto Japan & Expt Retrovirol Sect,Dept Intern, HIV AIDS Malignancy Branch,NIH, Bethesda, MD USA. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 56 BP S24 EP S25 DI 10.1016/S1201-9712(08)60058-2 PG 2 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300056 ER PT J AU Paulson, M Elloumi, H Holland, S AF Paulson, Michelle Elloumi, Houda Holland, Steven TI STAT3 mutations in Job's syndrome SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Paulson, Michelle; Elloumi, Houda; Holland, Steven] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 10 BP S5 EP S6 DI 10.1016/S1201-9712(08)60012-0 PG 2 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300010 ER PT J AU Petraitiene, R Petraitis, V Hope, W Mickiene, D Kelaher, A Murray, H Mya-San, C Hughes, J Cotton, M Bacher, J Bemjamin, D Walsh, T AF Petraitiene, Ruta Petraitis, Vidmantas Hope, William Mickiene, Diana Kelaher, Amy Murray, Heidi Mya-San, Christine Hughes, Johanna Cotton, Margaret Bacher, John Bemjamin, Danny Walsh, Thomas TI (1 -> 3)-beta-D-Glucan in cereobrospinal fluid is a surrogate marker for detection and therapeutic response of hematogenous Candida meningoencephalitis SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Petraitiene, Ruta; Petraitis, Vidmantas; Hope, William; Mickiene, Diana; Kelaher, Amy; Murray, Heidi; Mya-San, Christine; Hughes, Johanna; Cotton, Margaret; Walsh, Thomas] Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD USA. [Petraitiene, Ruta; Petraitis, Vidmantas; Mickiene, Diana] SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD USA. [Bacher, John] Off Res Serv, Vet Resources Program, Surg Serv, Bethesda, MD USA. [Bacher, John] Duke Univ, Durham, NC 27706 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 120 BP S48 EP S49 DI 10.1016/S1201-9712(08)60122-8 PG 2 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300120 ER PT J AU Petraitiene, R Petraitis, V Antachopoutos, C Hughes, JE Cotton, MP Harrington, SM Kasai, M Francesconi, A Beveridge, MG Sein, T Schaufele, RL Bacher, J Kontoyiannis, DP Walsh, TJ AF Petraitiene, Ruta Petraitis, Vidmantas Antachopoutos, Charalampos Hughes, Johanna E. Cotton, Margaret P. Harrington, Susan M. Kasai, Miki Francesconi, Andrea Beveridge, Mara G. Sein, Tin Schaufele, Robert L. Bacher, John Kontoyiannis, Dimitrios P. Walsh, Thomas J. TI Species-dependent differences in virulence of medically important zygomycetes in neutropenic hosts are related to sporangiospore germination, hyphal metabolism, and circulating molecular biomarker levels SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Petraitiene, Ruta; Petraitis, Vidmantas; Antachopoutos, Charalampos; Hughes, Johanna E.; Cotton, Margaret P.; Kasai, Miki; Francesconi, Andrea; Beveridge, Mara G.; Sein, Tin; Schaufele, Robert L.; Walsh, Thomas J.] Natl Canc Inst, NIH, Bethesda, MD USA. [Harrington, Susan M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Bacher, John] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Petraitiene, Ruta; Petraitis, Vidmantas; Sein, Tin] SAIC Frederick, Frederick, MD USA. [Kontoyiannis, Dimitrios P.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 121 BP S49 EP S49 DI 10.1016/S1201-9712(08)60123-X PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300121 ER PT J AU Sampaio, EP Zelazny, A Shea, Y Root, J Paulson, M Etloumi, H Olivier, K Holland, S AF Sampaio, Elizabeth Pereira Zelazny, Adrian Shea, Yvonne Root, Jeremy Paulson, Michele Etloumi, Houda Olivier, Ken Holland, Steven TI SOCS-1 and SOCS-3 are induced early in response to mycobacteria and decrease innate immunity in vitro SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Sampaio, Elizabeth Pereira; Zelazny, Adrian; Root, Jeremy; Paulson, Michele; Etloumi, Houda; Olivier, Ken; Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Shea, Yvonne] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 5 BP S3 EP S4 DI 10.1016/S1201-9712(08)60007-7 PG 2 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300005 ER PT J AU Uzel, G Kuhns, D Linton, G Quie, P Holland, S AF Uzel, Gutbu Kuhns, Douglas Linton, Gilda Quie, Paul Holland, Steven TI The first report of somatic mutation reversion X-linked chronic granulomatous disease SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Uzel, Gutbu; Kuhns, Douglas; Linton, Gilda; Quie, Paul; Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 11 BP S6 EP S6 DI 10.1016/S1201-9712(08)60013-2 PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300011 ER PT J AU Vinh, D Freeman, AF Hsu, A Holland, S AF Vinh, Donald Freeman, Alexandra F. Hsu, Amy Holland, Steven TI Filamentous fungal pneumonias in hyper IgE syndrome SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Vinh, Donald; Freeman, Alexandra F.; Hsu, Amy; Holland, Steven] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 12 BP S6 EP S6 DI 10.1016/S1201-9712(08)60014-4 PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300012 ER PT J AU Vinh, D Patel, S Uzel, G Anderson, V Freeman, A Olivier, K Elloumi, H Ding, L Kuhns, D Fink, D Long-Priel, D Deleo, F Sampaio, E Paulson, M Hsu, A Zetazny, A Root, J Frucht, D Holland, S AF Vinh, Donald Patel, Smita Uzel, Gulbu Anderson, Victoria Freeman, Alexandra Olivier, Kenneth Elloumi, Houda Ding, Li Kuhns, Douglas Fink, Daniette Long-Priel, Deborah DeLeo, Frank Sampaio, Elizabeth Paulson, Michelle Hsu, Amy Zetazny, Adrian Root, Jeremy Frucht, David Holland, Steven TI A novel autosomal-dominant late-onset immunodeficiency with susceptibility to mycobacteria, fungi, papillomavirus and myeloid malignancies SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Vinh, Donald; Patel, Smita; Uzel, Gulbu; Anderson, Victoria; Freeman, Alexandra; Olivier, Kenneth; Elloumi, Houda; Ding, Li; Kuhns, Douglas; Fink, Daniette; Long-Priel, Deborah; DeLeo, Frank; Sampaio, Elizabeth; Paulson, Michelle; Hsu, Amy; Zetazny, Adrian; Root, Jeremy; Frucht, David; Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 14 BP S7 EP S7 DI 10.1016/S1201-9712(08)60016-8 PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300014 ER PT J AU Zonios, D Falloon, J Bennett, J Shaw, P Chaitt, D Polis, M Kovacs, J Davey, R Lane, HC Masur, H Sereti, I AF Zonios, Dimitrios Falloon, Judith Bennett, John Shaw, Pamela Chaitt, Doreen Polis, Michael Kovacs, Joseph Davey, Richard Lane, H. Clifford Masur, Henry Sereti, Irini TI Idiopathic CD4+ lymphocytopenia: Natural history and prognostic factors SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 15 BP S7 EP S7 DI 10.1016/S1201-9712(08)60017-X PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300015 ER PT J AU Stetler-Stevenson, M AF Stetler-Stevenson, MaryAlice TI Flow cytometry of lymphoproliferative disorders and myeloma SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract ID IMMUNOPHENOTYPIC ANALYSIS; UTILITY; DISEASE C1 [Stetler-Stevenson, MaryAlice] NCI, NIH, Pathol Lab, Flow Cytometry Lab, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD JUN PY 2008 VL 30 SU 1 BP 23 EP 24 PG 2 WC Hematology SC Hematology GA 287SX UT WOS:000254937900028 ER PT J AU Jara-Acevedo, M Garcia-Montero, A Teodosio, C Escribano, L Alvarez, I Sanchez-Munoz, L Akin, C Metcalfe, D Orfao, A AF Jara-Acevedo, Maria Garcia-Montero, Andres Teodosio, Cristina Escribano, Luis Alvarez, Ivan Sanchez-Munoz, Laura Akin, Cem Metcalfe, Dean Orfao, Alberto TI Clinical and biological characterization of well-differentiated systemic mastocytosis (WDSM), a novel form of mastocytosis SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Jara-Acevedo, Maria; Garcia-Montero, Andres; Teodosio, Cristina; Orfao, Alberto] Canc Res Ctr, Salamanca, Spain. [Escribano, Luis; Alvarez, Ivan; Sanchez-Munoz, Laura] Hosp Virgen Valle, Ctr Estudios Mastocitosis Castilla Mancha, Toledo, Spain. [Akin, Cem] Univ Michigan, Ann Arbor, MI 48109 USA. [Metcalfe, Dean] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD JUN PY 2008 VL 30 SU 1 BP 54 EP 54 PG 1 WC Hematology SC Hematology GA 287SX UT WOS:000254937900065 ER PT J AU Drel, VR Pacher, P Ali, TK Shin, JH Julius, U El-Remessy, AB Obrosova, IG AF Drel, Viktor R. Pacher, Pal Ali, Tayyeba K. Shin, Jeho Julius, Ulrich El-Remessy, Azza B. Obrosova, Irina G. TI Aldose reductase inhibitor fidarestat counteracts diabetes-associated cataract formation, retinal oxidative-nitrosative stress, glial activation, and apoptosis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE aldose reductase; apoptosis; diabetic cataract; fidarestat; glial activation; nitrosative stress; poly(ADP-ribose) polymerase ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; PEROXYNITRITE DECOMPOSITION CATALYST; ENDOTHELIAL GROWTH-FACTOR; KINASE-C ACTIVATION; VASCULAR COMPLICATIONS; PERIPHERAL NEUROPATHY; LIPID-PEROXIDATION; TYROSINE NITRATION; EPITHELIAL-CELLS; POLYOL PATHWAY AB This study was aimed at evaluating the potent and specific aldose reductase inhibitor fidarestat, on diabetes-associated cataract formation, and retinal oxidative-nitrosative stress, glial activation, and apoptosis. Control and streptozotocin-diabetic rats were treated with or without fidarestat (16 mg kg(-1)d(-1)) for 10 weeks after an initial 2-week period without treatment. Lens changes were evaluated by indirect ophthalmoscopy and portable slit lamp. Nitrotyrosine, poly(ADP-ribose), and glial fibrillary acidic protein expression were assessed by immunohistochemistry. The rate of apoptosis was quantified in flat-mounted retinas by TUNEL assay with immunoperoxidase staining. To dissect the effects of high glucose exposure in retinal microvascular cells, primary bovine retinal pericytes and endothelial cells were cultured in 5 or 30 mM glucose, with or without fidarestat (10 mu M) for 3-14 days. Apoptosis was assessed by TUNEL assay, nitrotyrosine and poly(ADP-ribose) by immunocytochemistry, and Bax and Bcl-2 expression by Western blot analyses. Fidarestat treatment prevented diabetic cataract formation and counteracted retinal nitrosative stress, and poly(ADP-ribose) polymerase activation, as well as glial activation. The number of TUNEL-positive nuclei (mean SEM) was increased approximately 4-fold in diabetic rats vs. controls (207 +/- 33 vs. 49 +/- 4, p<0.01), and this increase was partially prevented by fidarestat (106 +/- 34, p<0.05 vs. untreated diabetic group). The apoptotic cell number increased with the prolongation of exposure of both pericytes and endothelial cells to high glucose levels. Fidarestat counteracted nitrotyrosine and poly(ADP-ribose) accumulation and apoptosis in both cell types. Antiapoptotic effect of fidarestat in high glucose-exposed retinal pericytes was not associated with the inhibition of Bax or increase in Bcl-2 expression. In conclusion, the findings, i) support an important role for aldose reductase in diabetes-associated cataract formation, and retinal oxidative-nitrosative stress, glial activation, and apoptosis, and ii) provide a rationale for the development of aldose reductase inhibitors, and, in particular, fidarestat, for the prevention and treatment of diabetic ocular complications. C1 [Drel, Viktor R.; Shin, Jeho; Obrosova, Irina G.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. [Ali, Tayyeba K.; El-Remessy, Azza B.] Univ Georgia, Coll Pharm, Program Clin & Expt Therapeut, Augusta, GA USA. [Julius, Ulrich] Univ Hosp, Med Clin 3, Dresden, Germany. RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM obrosoig@pbrc.edu RI Pacher, Pal/B-6378-2008; Drel, Viktor/G-8883-2016 OI Pacher, Pal/0000-0001-7036-8108; Drel, Viktor/0000-0003-4542-0132 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999]; NIDDK NIH HHS [DK 071566-01, R21 DK071566, R21 DK071566-01] NR 66 TC 42 Z9 45 U1 1 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JUN PY 2008 VL 21 IS 6 BP 667 EP 676 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 304SC UT WOS:000256128400001 PM 18506358 ER PT J AU Marx, CE Yuan, PX Kilts, JD Madison, RD Shampine, LJ Manji, HK AF Marx, Christine E. Yuan, Peixiong Kilts, Jason D. Madison, Roger D. Shampine, Lawrence J. Manji, Husseini K. TI Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Allopregnanolone; frontal cortex; neurosteroid; pregnenolone; valproate ID NEUROSTEROID ALLOPREGNANOLONE; BIPOLAR DISORDER; VALPROIC ACID; DOUBLE-BLIND; CELL-DEATH; CLOZAPINE; SCHIZOPHRENIA; OLANZAPINE; PROGESTERONE; NEUROGENESIS AB Many neuroactive steroids (NS) demonstrate neurotrophic and neuroprotective actions, including protection against apoptosis via Bcl-2 protein. NS are altered in post-mortem brain tissue from Subjects with bipolar disorder, and several agents with efficacy in mania elevate NS in rodents. We therefore hypothesized that lithium and valproate may elevate NS, and compensatory NS increases may occur in Bcl-2 knockout mice. NS levels (allopregnanolone, pregnenolone) were determined in frontal cortex by negative ion chemical ionization gas chromatography/mass spectrometry in male Wistar Kyoto rats treated chronically with lithium, valproate, or vehicle. NS were also investigated in heterozygous Bcl-2 knockout mice. Allopregnanolone levels are significantly elevated in lithium-treated (p<0.05), but not in valproate-treated, rats. Pregnenolone levels also tend to be higher following lithium treatment (p = 0.09). Knockout of Bcl-2 significantly increases pregnenolone levels in mice (p<0.01), while allopregnanolone levels are unaltered. NS induction may be relevant to mechanisms contributing to lithium therapeutic efficacy and neuroprotection. C1 [Marx, Christine E.; Kilts, Jason D.; Shampine, Lawrence J.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Madison, Roger D.] Duke Univ, Med Ctr, Dept Neurosurg, Durham, NC 27705 USA. [Marx, Christine E.; Kilts, Jason D.; Madison, Roger D.; Shampine, Lawrence J.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Yuan, Peixiong; Manji, Husseini K.] NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Marx, CE (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 508 Fulton St,Mental Hlth Serv Line 116A, Durham, NC 27705 USA. EM marx0001@mc.duke.edu FU VA Advanced Research Career Development Award; Durham VA REAP; Mid-Atlantic MIRECC; National Institute of Mental Health, NIH, Bethesda, MD; [K23 MH 65080] FX This work was supported by the following sources: K23 MH 65080 (C.E.M.), VA Advanced Research Career Development Award (C.E.M.), Durham VA REAP (R.D.M.), Mid-Atlantic MIRECC, and the National Institute of Mental Health, NIH, Bethesda, MD. We thank Gillian Parke for her excellent assistance with the manuscript. NR 34 TC 9 Z9 9 U1 3 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2008 VL 11 IS 4 BP 547 EP 552 DI 10.1017/S1461145708008444 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 422DC UT WOS:000264406300011 PM 18257969 ER PT J AU Zhou, X Zimonjic, DB Park, SW Yang, XY Durkin, ME Popescu, NC AF Zhou, Xiaoling Zimonjic, Drazen B. Park, Sang-Won Yang, Xu-Yu Durkin, Marian E. Popescu, Nicholas C. TI DLC1 suppresses distant dissemination of human hepatocellular carcinoma cells in nude mice through reduction of RhoA GTPase activity, actin cytoskeletal disruption and down-regulation of genes involved in metastasis SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE DLC1; tumor suppressor gene; Rho GTPase activating protein; liver cancer; metastasis; osteopontin; metalloproteinase-9 ID BREAST-CANCER CELLS; CHROMOSOME 8P DELETION; ACTIVATING PROTEIN; TUMOR-SUPPRESSOR; EXTRAHEPATIC METASTASES; GENOMIC ANALYSIS; OSTEOPONTIN; GROWTH; INVASION; OVEREXPRESSION AB The process of cell dissemination from the primary tumors to distant sites is the most harmful event during cancer progression, and the leading cause of cancer death. We have previously demonstrated that restoration of DLC1 tumor suppressor gene expression in the DLC1-negative Focus and 7703K human hepatocellular carcinoma (HCC) cell lines induced caspase-3 mediated apoptosis, reduced cell growth in vitro and tumorigenicity in vivo and diminished the ability to migrate through Matrigel, a property suggestive of metastatic potential in vivo. We now show that subcutaneous tumors developing after inoculation of Focus and 7703K cells into nude mice disseminate cells to liver and lung, and this process is markedly suppressed by restoration of DLC1 expression. Inhibition of tumor cell dissemination was associated with lower levels of RhoA activity, an increase in rounded cells and a reduction in actin stress fibers and focal adhesion molecules that are of critical importance in cancer cell invasion and metastasis. In addition, DLC1 down-regulated the expression of osteopontin and matrix metalloproteinase-9, which are highly up-regulated in most primary HCC with associated metastases. These observations implicate the DLC1 gene in suppression of HCC cell dissemination and identify novel cellular and genetic alterations that contribute to prevention of metastasis, a life-threatening event in cancer progression. C1 [Zhou, Xiaoling; Zimonjic, Drazen B.; Park, Sang-Won; Yang, Xu-Yu; Durkin, Marian E.; Popescu, Nicholas C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, 37 Covent Dr,MSC 4262, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI yang, xuyu/D-1414-2012 FU Intramural NIH HHS NR 52 TC 30 Z9 32 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 2008 VL 32 IS 6 BP 1285 EP 1291 PG 7 WC Oncology SC Oncology GA 305PU UT WOS:000256191100015 PM 18497990 ER PT J AU Chen, YH Chen, F Yang, JY Yang, MQ AF Chen, Yuehui Chen, Feng Yang, Jack Y. Yang, Mary Qu TI Ensemble voting system for multiclass protein fold recognition SO INTERNATIONAL JOURNAL OF PATTERN RECOGNITION AND ARTIFICIAL INTELLIGENCE LA English DT Article DE protein fold recognition; particle swarm optimization (PSO); Tabu search; k-NN; probabilistic neural networks; ensemble learning ID STRUCTURAL CLASS PREDICTION; STATISTICAL-METHOD; MEMBRANE-PROTEINS; SEQUENCE; CLASSIFICATION; PROFILES AB Protein structure classification is an important issue in understanding the associations between sequence and structure as well as possible functional and evolutionary relationships. Recently structural genomes initiatives and other high-throughput experiments have populated the biological databases at a rapid pace. In this paper, three types of classifiers, k nearest neighbors, class center and nearest neighbor and probabilistic neural networks and their homogenous ensemble for multiclass protein fold recognition problem are evaluated firstly, and then a heterogenous ensemble Voting System is designed for the same problem. The different features and/or their combinations extracted from the protein fold dataset are used in these classification models. The heterogenous classification results are then put into a voting system to get the final result. The experimental results show that the proposed method can improve prediction accuracy by 4%-10% on a benchmark dataset containing 27 SCOP folds. C1 [Chen, Yuehui] Univ Jinan, Sch Informat Sci & Engn, Jinan 250022, Peoples R China. [Chen, Feng] Univ Elect Sci & Technol China, Sch Software, Chengdu 610054, Peoples R China. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. [Yang, Mary Qu] US Dept HHS, Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20852 USA. RP Chen, YH (reprint author), Univ Jinan, Sch Informat Sci & Engn, Jinan 250022, Peoples R China. EM yhchen@ujn.edu.cn; chenfeng_ci@163.com; jyang@bwh.harvard.edu; yangma@mail.NIH.gov NR 38 TC 7 Z9 7 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-0014 J9 INT J PATTERN RECOGN JI Int. J. Pattern Recognit. Artif. Intell. PD JUN PY 2008 VL 22 IS 4 BP 747 EP 763 DI 10.1142/S0218001408006454 PG 17 WC Computer Science, Artificial Intelligence SC Computer Science GA 327XM UT WOS:000257761800006 ER PT J AU Krueger, F Heinecke, A Landgraf, S van der Meer, E AF Krueger, Frank Heinecke, Armin Landgraf, Seffen van der Meer, Elke TI Brain network for arithmetic as evaluated with functional Magnetic Resonance Imaging (fMRI) and Granger Causality Mapping (GCM) SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 [Krueger, Frank] NINDS, NIH, Dept Cognit Neurosci, Bethesda, MD 20892 USA. [Heinecke, Armin] Brain Innovat, Maastricht, Netherlands. [van der Meer, Elke] Humboldt Univ, Inst Psychol, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 2008 VL 43 IS 3-4 BP 47 EP 47 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 349EO UT WOS:000259264300529 ER PT J AU Bornstein, M Esposito, G deFalco, S Venuti, P AF Bornstein, Marc Esposito, Gianluca deFalco, Simona Venuti, Paola TI Mother And Child Play In Down Syndrome and typically developing dyads SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 [Bornstein, Marc] NICHD, NIH, CFR, Bethesda, MD USA. [deFalco, Simona; Venuti, Paola] Univ Trent, DiSCoF Cognit Sci, Tovereto, TN, Italy. RI Esposito, Gianluca/B-1374-2012 OI Esposito, Gianluca/0000-0002-9442-0254 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 2008 VL 43 IS 3-4 BP 487 EP 487 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 349EO UT WOS:000259264305670 ER PT J AU Xu, G Li, Y Yang, J Yin, X Zhou, X Liu, M Zhao, D AF Xu, G. Li, Y. Yang, J. Yin, X. Zhou, X. Liu, M. Zhao, D. TI Mycobacterium bovis Mce4E protein may play a role in modulating cytokine expression profile in alveolar macrophage SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE Mycobacterium bovis; Mce4E protein; bovine alveolar macrophage; real-time RT-PCR ID COMPLETE GENOME SEQUENCE; CELL-ENTRY PROTEINS; NITRIC-OXIDE; TUBERCULOSIS; DISRUPTION; OPERON; ALPHA; INFECTION; VIRULENCE; NECROSIS AB SETTING: A large body of research has confirmed that mammalian cell entry proteins (Mce) are related to tuberculosis virulence. OBJECTIVE: To obtain an insight into the effect of Mce family protein on the pathogenesis of Mycobacterium bovis, we expressed recombinant Mce4E protein in Escherichia coli, and investigated its effect on the expression of tumor necrosis factor alpha (TNF-alpha), inducible NO, interleukin 6 (IL-6) and interleukin 12 (IL-12) in alveolar macrophage by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Our study demonstrated that after stimulation of alveolar macrophages by Mce4E protein for 48 h, the expression of TNF-alpha was induced, with an enhanced IL-6 mRNA level (P < 0.05) and no changes in IL-12 expression in the macrophages. In addition to the changes in the cytokine expression profile in macrophages, the expression of inducible NO synthase was reduced (P < 0.05). Our MTT [3,(4,5 dimethylthiazol-2yl) -2,5 diphenyltetrazolium bromide] analysis of the macrophage also demonstrated that Mce4E protein could inhibit macrophage activity. CONCLUSION: Our data suggest that Mce4E proteins can induce host inflammation response to M. bovis and may play an important role in host/pathogen interactions. C1 [Xu, G.; Yang, J.; Yin, X.; Zhou, X.; Liu, M.; Zhao, D.] China Agr Univ, Coll Vet Med, Natl Anim Transmissible Spongiform Encephalopathi, Beijing 100094, Peoples R China. [Xu, G.] Ningxia Univ, Coll Life Sci, Yinchuan, Peoples R China. [Li, Y.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Zhao, D (reprint author), China Agr Univ, Coll Vet Med, Natl Anim Transmissible Spongiform Encephalopathi, Yuanmingyuan Xi Lu 2,Haidian Dist, Beijing 100094, Peoples R China. EM zhaodm@cau.edu.cn RI Zhou, Xiangmei/H-6380-2011 NR 35 TC 4 Z9 4 U1 1 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JUN PY 2008 VL 12 IS 6 BP 664 EP 669 PG 6 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 307NT UT WOS:000256326300015 PM 18492334 ER PT J AU Knox, JJ Gill, S Synold, TW Biagi, JJ Major, P Feld, R Cripps, C Wainman, N Eisenhauer, E Seymour, L AF Knox, Jennifer J. Gill, Sharlene Synold, Timothy W. Biagi, James J. Major, Pierre Feld, Ron Cripps, Christine Wainman, Nancy Eisenhauer, Elizabeth Seymour, Lesley TI A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: A study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168) SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE hepatocellular carcinoma; SB-715992; phase II trial; hepatoma; mitotic kinesin spindle protein (KSP) ID CHEMOEMBOLIZATION; RESISTANCE; CIRRHOSIS AB Hepatocellular carcinoma (HCC) remains a lethal treatment-resistant cancer with a median survival of < 6 months in patients not considered candidates for radical surgical treatments. SB-715992 is a novel cytotoxic agent implicated in the inhibition of mitotic kinesin spindle protein (KSP). Based on evidence from preclinical models and phase I trials, we conducted a phase II trial of SB-715992 in chemo-naive patients with advanced HCC. A non-randomized, non-blinded multicentre two-stage phase II study was completed examining the efficacy, toxicity, and pharmacokinetics of SB-715992 at 18 mg/m(2) IV q 3 weeks, in patients with measurable locally advanced, metastatic or recurrent HCC. The predictive value of KSP in archival tumour was assessed. Fifteen patients with metastatic HCC received a median of 3 cycles of SB-715992. The most common grade 3+ toxicities were granulocytopenia, leukocytopenia, diarrhea and liver transaminase rise. Overall confirmed response rate was 0%. Seven (46%) patients had a best response of stable disease at the 8-week evaluation (median duration 3.9 months) Median time to progression was 1.61 months (95%CI = 1.31-3.94 months) SB-715992 plasma concentrations were comparable to those observed in the phase I studies. Expression of KSP by immunohistochemistry was observed in only four of eight evaluable samples with strong expression reported in only two. No correlation was observed between intensity of KSP staining and clinical outcome. Among these patients with preserved hepatic function and good performance status, SB-715992 was generally well tolerated. However, no conclusive evidence of benefit was seen with SB-715992 monotherapy in HCC. C1 [Knox, Jennifer J.; Feld, Ron] Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. [Gill, Sharlene] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Synold, Timothy W.] City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA. [Biagi, James J.] Queens Univ, Dept Oncol, Kingston, ON K7L 5P9, Canada. [Wainman, Nancy; Eisenhauer, Elizabeth; Seymour, Lesley] Queens Univ, NCI, Canada Clin Trials Grp, Kingston, ON K7L 3N6, Canada. [Cripps, Christine] Ottawa Hosp Reg Canc Ctr, Ottawa, ON K1H 1C4, Canada. [Major, Pierre] Hamilton Reg Canc Ctr, Hamilton, ON L8V 5C2, Canada. RP Knox, JJ (reprint author), Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. EM jennifer.knox@uhn.on.ca NR 21 TC 31 Z9 33 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUN PY 2008 VL 26 IS 3 BP 265 EP 272 DI 10.1007/s10637-007-9103-2 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 291JU UT WOS:000255194000009 PM 18196204 ER PT J AU Thill, M Strunnikova, NV Berna, MJ Gordiyenko, N Schmid, K Cousins, SW Thompson, DJS Csaky, KG AF Thill, Michelle Strunnikova, Natalya V. Berna, Marc J. Gordiyenko, Nataliya Schmid, Kristin Cousins, Scott W. Thompson, Darby J. S. Csaky, Karl G. TI Late outgrowth endothelial progenitor cells in patients with age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 04, 2006 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; C-REACTIVE PROTEIN; UMBILICAL-CORD BLOOD; SMOOTH-MUSCLE-CELLS; BONE-MARROW; GROWTH-FACTOR; STEM-CELLS; CARDIOVASCULAR-DISEASE AB PURPOSE. To evaluate the feasibility of isolating and expanding endothelial progenitor cells (EPCs), in the form of late outgrowth endothelial progenitor cells (OECs), from the peripheral blood of an aged population, particularly patients affected by different forms of AMD. METHODS. Peripheral blood mononuclear cells were collected from young control subjects (n = 18) and from elderly subjects with non-AMD/low-risk dry AMD (n = 15), high-risk dry AMD (n = 6), or neovascular AMD (nvAMD; n = 32); cultured in established conditions; and observed for appearance of OEC clusters and growth characteristics on expansion. Expression of VEGF receptor-2 (KDR) in OECs after expansion was determined by Western blot. Plasma samples of study subjects were analyzed for CRP and VEGF levels. RESULTS. OEC cultures were successfully generated from a similar number of subjects in each group. After adjustment for all other variables, subjects with high-risk dry AMD had a 5.6-fold higher number of OEC clusters per 20 mL blood, and subjects with nvAMD had a 5.1-fold high number than did subjects with non-AMD/low-risk dry AMD (P < 0.05). High-risk dry AMD generated 63 times more (NS) and nvAMD 32-times more (P < 0.05) OECs on expansion of clusters than did non-AMD/low-risk dry AMD. Population doubling occurred significantly faster in cultures from nvAMD eyes compared to non-AMD/low-risk dry AMD eyes. In addition, a significant correlation between the number of OEC clusters, expanded OECs and levels of KDR was demonstrated. CONCLUSIONS. An OEC population was isolated and expanded from the blood of elderly control and AMD-affected patients and demonstrated significantly higher number of initial OEC clusters and expansion potential of OECs in patients at risk for or already affected by nvAMD. OECs may be used for further phenotypic, genetic, and functional analyses in patients with nvAMD. C1 [Cousins, Scott W.; Csaky, Karl G.] Duke Univ, Ctr Eye, Durham, NC 27710 USA. [Thill, Michelle; Strunnikova, Natalya V.; Gordiyenko, Nataliya] NIDDK, Natl Inst Hlth, NEI, Bethesda, MD USA. [Berna, Marc J.] NIDDK, Natl Inst Hlth, Digest Dis Branch, Bethesda, MD USA. [Thill, Michelle; Berna, Marc J.] Univ Klinikum Hamburg Eppendorf, Hamburg, Germany. [Schmid, Kristin] Loma Linda Univ, Sch Med, Loma Linda, CA USA. [Thompson, Darby J. S.] EMMES Corp, Rockville, MD USA. RP Csaky, KG (reprint author), Duke Univ, Ctr Eye, DUMC Box 3802, Durham, NC 27710 USA. EM karl.csaky@duke.edu NR 85 TC 24 Z9 25 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2008 VL 49 IS 6 BP 2696 EP 2708 DI 10.1167/iovs.07-0955 PG 13 WC Ophthalmology SC Ophthalmology GA 307GG UT WOS:000256306800054 PM 18515596 ER PT J AU Laeyendecker, O Rothman, RE Henson, C Horne, BJ Ketlogetswe, KS Kraus, CK Shahan, J Kelen, GD Quinn, TC AF Laeyendecker, Oliver Rothman, Richard E. Henson, Charlamaine Horne, Bobbi Jo Ketlogetswe, Kerunne S. Kraus, Chadd K. Shahan, Judy Kelen, Gabor D. Quinn, Thomas C. TI The effect of viral suppression on cross-sectional incidence testing in the Johns Hopkins Hospital Emergency Department SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE emergency department; incidence testing; viral suppression ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; EARLY HIV-1 INFECTION; ENZYME-IMMUNOASSAY; SENSITIVE HIV-1; AVIDITY INDEX; SEROCONVERSION; TYPE-1; ASSAY; RISK AB Objective(s): To determine the effect of viral suppression oil cross-sectional incidence testing. Methods: In 2001 and 2003, patients entering the Johns Hopkins Hospital (JHH) Emergency Department (ED) were enrolled into an interview-based identity-unlinked serosurvey. All HIV-positive samples were tested by the Vironostika-less sensitive (LS) enzyme immunoassay (ETA) (Organon-Teknika, Charteston, SC) and an avidity assay to determine recent HIV infection. Additionally 16 samples from 8 previously characterized elite suppressors (ES) were tested by cross-sectional incidence assays. Results: HIV prevalence was 12% for the 2001 survey and 11% for the 2003 survey. Of the HIV-infected subjects, 18% did not know they were infected. The Vironostika-LS ETA determined that 6% (11 of 183) and 7% (17 of 243) of HIV-positive individuals in 2001 and 2003, respectively, were recently infected. Avidity testing confirmed that 6 of I I in 2001 and 5 of 17 in 2003 were newly infected, leaving 17 discrepant samples. All 17 discrepant samples were Western blot-positive and viral load undetectable, and 7 of 17 had antiretroviral drugs (ARVs) in their serum. Ten individuals were virally suppressed without ARVs and seemed incident by the Vironostika-LS EIA but chronic by avidity testing. These 10 subjects had similar testing profiles to the known 16 ES samples, because 9 of 16 were incident by the Vironostika-LS EIA and 0 of 16 were incident by avidity testing. Conclusions: By removing the viral load-negative individuals and confirming the initial Vironostika-LS ETA results by avidity testing, the incidence estimate was lowered from 1.73% to 0.94% per year in 2001 and from 1.90% to 0.56% per year in 2003. Viral suppression affects the performance of the cross-sectional incidence tests, which rely on antibody titer. In addition, 2% (10 of 426) of all HIV-infected individuals who use the JHH ED for medical care seem to suppress HIV to undetectable levels without ARVs. C1 [Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Baltimore, MD USA. [Laeyendecker, Oliver; Rothman, Richard E.; Henson, Charlamaine; Horne, Bobbi Jo; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Rothman, Richard E.; Ketlogetswe, Kerunne S.; Kraus, Chadd K.; Shahan, Judy; Kelen, Gabor D.] Johns Hopkins Univ, Dept Emergency Med, Baltimore, MD USA. RP Laeyendecker, O (reprint author), 1721 E Madison Ave,Ross Bldg,Room 1155, Baltimore, MD 21205 USA. EM olaeyenl@jhmi.edu RI Laeyendecker, Oliver/B-9331-2009; OI Rothman, Richard/0000-0002-1017-9505; Kelen, Gabor/0000-0002-3236-8286; Laeyendecker, Oliver/0000-0002-6429-4760 FU Intramural NIH HHS [Z01 AI000361-25]; NIAID NIH HHS [U01 AI068613, U01 AI068613-03, U01-AI-068613] NR 19 TC 46 Z9 48 U1 0 U2 0 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 JUN 1 PY 2008 VL 48 IS 2 BP 211 EP 215 DI 10.1097/QAI.0b013e3181743980 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 306WO UT WOS:000256278800014 PM 18520680 ER PT J AU Wakeman, B Babu, D Tarleton, J MacDonald, IM AF Wakeman, Bradley Babu, Deepti Tarleton, Jack MacDonald, Ian M. TI Extraocular muscle hypertrophy in myotonia congenita SO JOURNAL OF AAPOS LA English DT Article ID DOMINANT AB Myotonia congenita (MC) is a rare disorder of skeletal muscle caused by mutations in the CLCN1 gene,(1,2) which encodes the chloride ion channel found in the t-tubule of skeletal muscle. MC is characterized by impaired relaxation of voluntary muscle after sudden contraction that diminishes with muscle activity, known as the "warm-up effect." Individuals with MC can develop muscular hypertrophy despite little physical activity. Esotropia and reduced saccadic velocities have been reported in the dominant form of MC. We report two cases in which orbital magnetic resonance imaging (MRI) imaging showed extraocular muscle hypertrophy. C1 [Wakeman, Bradley; MacDonald, Ian M.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. [Babu, Deepti] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada. [Tarleton, Jack] Mission Hosp, Fullerton Genet Lab, Asheville, NC USA. [MacDonald, Ian M.] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Wakeman, B (reprint author), Univ Alberta Hosp, 2-133 Clin Sci Bldg, Edmonton, AB T6G 2G3, Canada. EM Brad.Wakeman@capitalhealth.ca OI MacDonald, Ian/0000-0001-7472-8385 NR 11 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD JUN PY 2008 VL 12 IS 3 BP 294 EP 296 DI 10.1016/j.jaapos.2007.12.002 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 324YU UT WOS:000257556100016 PM 18313341 ER PT J AU Cohen, SG AF Cohen, Sheldon G. TI Food allergens: Landmarks along a historic trail SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material C1 NIAID, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, Natl Lib Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2008 VL 121 IS 6 BP 1521 EP 1524 DI 10.1016/j.jaci.2008.04.027 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 313WW UT WOS:000256771700040 PM 18539201 ER PT J AU Dorr, LD Raya, J Long, WT Boutary, M Sirianni, LE AF Dorr, Lawrence D. Raya, Julio Long, William T. Boutary, Myriam Sirianni, Leigh Ellen TI Multimodal analgesia without parenteral narcotics for total knee arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE pain; pain medications; narcotics; total knee arthroplasty; multimodal treatment ID PATIENT-CONTROLLED ANALGESIA; EPIDURAL MORPHINE FORMULATION; TOTAL-HIP-ARTHROPLASTY; POSTOPERATIVE PAIN; INTRATHECAL MORPHINE; JOINT ARTHROPLASTY; BLOCK; REPLACEMENT; BUPIVACAINE; PREVENTION AB Use of parenteral narcotics after total knee arthroplasty is considered by most orthopedic surgeons to be the standard of care. This study tested the hypothesis that a multimodal oral pain medication protocol could control pain and minimize complications of parenteral narcotics. Postoperative oral analgesia was augmented with either continuous epidural infusion or continuous femoral infusion using ropivacaine only. Seventy patients had total knee arthroplasty with a protocol that included preemptive oral analgesics, epidural anesthesia, pericapsular analgesic injection, and postoperative analgesia without parenteral opioids. The average daily pain score was less than 4 out of 10, nausea occurred in 15 patients (21 %), emesis in 1 patient (1.4%), and there were no severe complications. This study proved the hypothesis that pain after total knee arthroplasty could be effectively managed without routine use of parenteral opioids. C1 [Dorr, Lawrence D.; Raya, Julio; Long, William T.; Boutary, Myriam; Sirianni, Leigh Ellen] NIAMSD, Inglewood, CA 90301 USA. RP Dorr, LD (reprint author), NIAMSD, 501 E Harding St,3rd Floor, Inglewood, CA 90301 USA. NR 31 TC 24 Z9 29 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 2008 VL 23 IS 4 BP 502 EP 508 DI 10.1016/j.arth.2007.10.004 PG 7 WC Orthopedics SC Orthopedics GA 311WX UT WOS:000256632200003 PM 18514865 ER PT J AU Rostovtseva, TK Bezrukov, SM AF Rostovtseva, Tatiana K. Bezrukov, Sergey M. TI VDAC regulation: role of cytosolic proteins and mitochondrial lipids SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE apoptosis; mitochondria; mitochondria outer membrane; voltage dependent anion channel; VDAC; channel gating; tubulin; tBid; cardiolipin; lipid packing stress ID DEPENDENT ANION CHANNEL; PERMEABILITY TRANSITION PORE; LATERAL PRESSURE PROFILE; OUTER-MEMBRANE CHANNEL; CYTOCHROME-C; CELL-DEATH; POSSIBLE INVOLVEMENT; YEAST MITOCHONDRIA; NEUROSPORA-CRASSA; NONBILAYER LIPIDS AB It was recently asserted that the voltage-dependent anion channel (VDAC) serves as a global regulator, or governor, of mitochondrial function (Lemasters and Holmuhamedov, Biochim Biophys Acta 1762:181-190, 2006). Indeed, VDAC, positioned on the interface between mitochondria and the cytosol (Colombini, Mol Cell Biochem 256:107-115, 2004), is at the control point of mitochondria life and death. This large channel plays the role of a "switch" that defines in which direction mitochondria will go: to normal respiration or to suppression of mitochondria metabolism that leads to apoptosis and cell death. As the most abundant protein in the mitochondrial outer membrane (MOM), VDAC is known to be responsible for ATP/ADP exchange and for the fluxes of other metabolites across MOM. It controls them by switching between the open and "closed" states that are virtually impermeable to ATP and ADP. This control has dual importance: in maintaining normal mitochondria respiration and in triggering apoptosis when cytochrome c and other apoptogenic factors are released from the intermembrane space into the cytosol. Emerging evidence indicates that VDAC closure promotes apoptotic signals without direct involvement of VDAC in the permeability transition pore or hypothetical Bax-containing cytochrome c permeable pores. VDAC gating has been studied extensively for the last 30 years on reconstituted VDAC channels. In this review we focus exclusively on physiologically relevant regulators of VDAC gating such as endogenous cytosolic proteins and mitochondrial lipids. Closure of VDAC induced by such dissimilar cytosolic proteins as pro-apoptotic tBid and dimeric tubulin is compared to show that the involved mechanisms are rather distinct. While tBid mostly modulates VDAC voltage gating, tubulin blocks the channel with the efficiency of blockage controlled by voltage. We also discuss how characteristic mitochondrial lipids, phospatidylethanolamine and cardiolipin, could regulate VDAC gating. Overall, we demonstrate that VDAC gating is not just an observation made under artificial conditions of channel reconstitution but is a major mechanism of MOM permeability control. C1 [Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] NICHD, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RP Rostovtseva, TK (reprint author), NICHD, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bldg 9,Rm 1E-106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rostovtt@mail.nih.gov FU Intramural Research Program of the NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The authors are grateful to Adrian Parsegian for fruitful discussions and reading parts of the manuscript. This study was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 80 TC 124 Z9 129 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD JUN PY 2008 VL 40 IS 3 BP 163 EP 170 DI 10.1007/s10863-008-9145-y PG 8 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 351PY UT WOS:000259437700007 PM 18654841 ER PT J AU Martinez, HM Maizel, JV Shapiro, BA AF Martinez, Hugo M. Maizel, Jacob V., Jr. Shapiro, Bruce A. TI RNA2D3D: A program for generating, viewing, and comparing 3-dimensional models of RNA SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article DE RNA secondary structure; RNA 3D structure; RNA modeling; molecular modeling; and nanobiology ID PARALLEL GENETIC ALGORITHM; SECONDARY STRUCTURE; STRUCTURE PREDICTION; HAMMERHEAD RIBOZYME; RIBOSOMAL-SUBUNIT; DYNAMICS; TOOL AB Using primary and secondary structure information of an RNA molecule, the program RNA2D3D automatically and rapidly produces a first-order approximation of a 3-dimensional conformation consistent with this information. Applicable to structures of arbitrary branching complexity and pseudoknot content, it features efficient interactive graphical editing for the removal of any overlaps introduced by the initial generating procedure and for making conformational changes favorable to targeted features and subsequent refinement. With emphasis on fast exploration of alternative 3D conformations, one may interactively add or delete base-pairs, adjacent stems can be coaxially stacked or unstacked, single strands can be shaped to accommodate special constraints, and arbitrary subsets can be defined and manipulated as rigid bodies. Compaction, whereby base stacking within stems is optimally extended into connecting single strands, is also available as a means of strategically making the structures more compact and revealing folding motifs. Subsequent refinement of the first-order approximation, of modifications, and for the imposing of tertiary constraints is assisted with standard energy refinement techniques. Previously determined coordinates for any part of the molecule are readily incorporated, and any part of the modeled structure can be output as a PDB or XYZ file. Illustrative applications in the areas of ribozymes, viral kissing loops, viral internal ribosome entry sites, and nanobiology are presented. C1 [Martinez, Hugo M.; Maizel, Jacob V., Jr.; Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Bldg 469,Room 150, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov FU Intramural NIH HHS [ZIA BC008382-28] NR 34 TC 83 Z9 85 U1 1 U2 8 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2008 VL 25 IS 6 BP 669 EP 683 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 301GF UT WOS:000255883700011 PM 18399701 ER PT J AU Matsuki, T Pramatarova, A Howell, BW AF Matsuki, Tohru Pramatarova, Albena Howell, Brian W. TI Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis SO JOURNAL OF CELL SCIENCE LA English DT Article DE Dab1; Crk; CrkL; dendritogenesis; hippocampus ID DAB1 TYROSINE PHOSPHORYLATION; APOE RECEPTOR 2; BRAIN-DEVELOPMENT; PHOSPHATIDYLINOSITOL 3-KINASE; STIMULATED NEURONS; VLDL RECEPTOR; MICE LACKING; DISABLED 1; MOUSE; PROTEIN AB The reelin signaling pathway regulates nervous system function after birth, in addition to its role in regulating neuronal positioning during embryogenesis. The receptor-dependent, reelin-induced tyrosine phosphorylation of the Dab1 docking protein is an established prerequisite for biological responses to this ligand. Here we show that the inactivation of a conditional Dab1 allele reduces process complexity in correctly positioned neurons in the CA1 region of the mouse hippocampus after birth. Reelin stimulation of cultured hippocampal neurons enhances dendritogenesis by approximately twofold and in a manner dependent on Src family kinases. This enhancement is blocked by reducing expression of Crk family proteins, adaptor molecules that interact with Dab1 in a tyrosine phosphorylation-dependent manner. Retrovirally expressed inhibitory RNAs used to reduce Crk and CrkL expression did not block BDNF-enhanced dendritogenesis or influence axonogenesis. Together, this demonstrates that the Crk family proteins are important downstream components of the reelin signaling pathway in the regulation of postnatal hippocampal dendritogenesis. C1 [Matsuki, Tohru; Pramatarova, Albena; Howell, Brian W.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Howell, BW (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM howellb@ninds.nih.gov OI Howell, Brian/0000-0002-0204-0773 FU Intramural NIH HHS [NIH0010383556, Z01 NS002987-08] NR 38 TC 46 Z9 47 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN 1 PY 2008 VL 121 IS 11 BP 1869 EP 1875 DI 10.1242/jcs.027334 PG 7 WC Cell Biology SC Cell Biology GA 303VR UT WOS:000256069500012 PM 18477607 ER PT J AU Lee, H Lim, C Lee, J Kim, N Bang, S Lee, H Min, B Park, G Noda, M Stetler-Stevenson, WG Oh, J AF Lee, Hongsik Lim, Chaeseung Lee, Jungeun Kim, Nayoung Bang, Sangsu Lee, Hojae Min, Bonhong Park, Gilhong Noda, Makoto Stetler-Stevenson, William G. Oh, Junseo TI TGF-beta signaling preserves RECK expression in activated pancreatic stellate cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE pancreatic stellate cells; fibrosis; RECK; TGF-beta ID MATRIX GENE-EXPRESSION; TISSUE INHIBITORS; TRANSFORMING GROWTH-FACTOR-BETA-1; INTERSTITIAL FIBROSIS; DIFFERENT ROLES; LIVER FIBROSIS; SMAD3; METALLOPROTEINASES; CULTURE; IDENTIFICATION AB Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic fibrosis, but the detailed mechanism for dysregulated accumulation of extracellular matrix (ECM) remains unclear. Cultured rat PSCs become activated by profibrogenic mediators, but these mediators failed to alter the expression levels of matrix metalloproteinases (MMPs) to the endogenous tissue inhibitors of metalloproteinases (TIMPs). Here, we examined the expression of RECK, a novel membrane-anchored MMP inhibitor, in PSCs. Although RECK mRNA levels were largely unchanged, RECK protein expression was barely detected at 2, 5 days after plating PSCs, but appeared following continued in vitro culture and cell passage which result in PSC activation. When PSCs at 5 days after plating (PSCs-5d) were treated with pepstatin A, an aspartic protease inhibitor, or TGF-beta 1, a profibrogenic mediator, RECK protein was detected in whole cell lysates. Conversely, Smad7 overexpression or suppression of Smad3 expression in PSCs after passage 2 (PSCsP2) led to the loss of RECK protein expression. These findings suggest that RECK is post-translationally processed in pre-activated PSCs but protected from proteolytic degradation by TGF-beta signaling. Furthermore, collagenolytic activity of PSCs-5d was greatly reduced by TGF-beta 1, whereas that of PSCs-beta 2 was increased by anti-RECK antibody. Increased RECK levels were also observed in cerulein-induced acute pancreatitis. Therefore, our results suggest for the first time proteolytic processing of RECK as a mechanism regulating RECK activity, and demonstrate that TGF-beta signaling in activated PSCs may promote ECM accumulation via a mechanism that preserves the protease inhibitory activity of RECK. C1 [Lee, Hongsik] Ansan Korea Univ Hosp, Dept Internal Med, Ansan, Gyeonggi Do, South Korea. [Lim, Chaeseung] Ansan Korea Univ Hosp, Dept Lab Med, Ansan, Gyeonggi Do, South Korea. [Lee, Jungeun; Kim, Nayoung; Bang, Sangsu; Oh, Junseo] Korea Univ, Grad Sch Med, Cellular Oncol Lab, Seoul, South Korea. [Lee, Hojae] KRIBB, Div Mol Therapeut, Taejon, South Korea. [Min, Bonhong] Korea Univ, Grad Sch Med, Dept Pharmacol, Seoul, South Korea. [Park, Gilhong] Korea Univ, Grad Sch Med, Dept Biochem, Seoul, South Korea. [Noda, Makoto] Kyoto Univ, Grad Sch Med, Dept Mol Oncol, Kyoto, Japan. [Stetler-Stevenson, William G.] Cell & Canc Biol Branch, Natl Canc Inst, Bethesda, MD USA. RP Oh, J (reprint author), Korea Univ, Grad Sch Med, Cellular Oncol Lab, Gojan 1 Dong, Ansan 425707, Gyeonggi Do, South Korea. EM ohjs@korea.ac.kr RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; bang, sangsu/0000-0002-9092-0075 NR 30 TC 15 Z9 18 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 1 PY 2008 VL 104 IS 3 BP 1065 EP 1074 DI 10.1002/jcb.21692 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 311VU UT WOS:000256629300030 PM 18300271 ER PT J AU Mosha, KS Zeldin, DC Sithu, SD Sen, U Tyagi, N Kumar, M Hughes, WM Metreveli, N Rosenberger, DSE Singh, M Vacek, TP Rodriguez, WE Ayotunde, A Tyagi, SC AF Mosha, Karni S. Zeldin, Darryl C. Sithu, Srinivas D. Sen, Utpal Tyagi, Neetu Kumar, Munish Hughes, William M., Jr. Metreveli, Naira Rosenberger, Dorothea S. E. Singh, Mahavir Vacek, Thomas P. Rodriguez, Walter E. Ayotunde, Adeagbo Tyagi, Suresh C. TI Cytochrome p450 (CYP) 2J2 gene transfection attenuates MMP-9 via inhibition of NF-kappa beta in hyperhomocysteinemia SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; EPOXYGENASE-DERIVED EICOSANOIDS; HYPERPOLARIZING FACTOR EDHF; SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; EPOXYEICOSATRIENOIC ACIDS; MATRIX METALLOPROTEINASES; MOLECULAR-CLONING; PROTEIN-KINASE; HEART-FAILURE AB Hyperhomocysteinemia (HHcy) is associated with atherosclerotic events involving the modulation of arachidonic acid (AA) metabolism and the activation of matrix metalloproteinase-9 (MMP-9). Cytochrome P450 (CYP) epoxygenase-2J2 (CYP2J2) is abundant in the heart endothelium, and its AA metabolites epoxyeicosatrienoic acids (EETs) mitigates inflammation through NF-kappa beta. However, the underlying molecular mechanisms for MMP-9 regulation by CYP2J2 in HHcy remain obscure. We sought to determine the molecular mechanisms by which P450 epoxygerase gene transfection or EETs supplementation attenuate homocysteine (Hcy)-induced MMP-9 activation. CYP2J2 was over-expressed in mouse aortic endothelial cells (MAECs) by transfection with the pcDNA3.1/CYP2J2 vector. The effects of P450 epoxygenase transfection or exogenous supplementation of EETs on NF-kappa beta-mediated MMP-9 regulation were evaluated using Western blot, in-gel gelatin zymography, electromobility shift assay, immunocytochemistry. The result suggested that Hcy downregulated CYP2J2 protein expression and dephosphorylated PI3K-dependent AKT signal. Hcy induced the nuclear translocation of NF-kappa beta via downregulation of IK beta alpha (endogenous cytoplasmic inhibitor of NF-kappa beta). Hcy induced MMP-9 activation by increasing NF-kappa beta-DNA binding. Moreover, P450 epoxygerase transfection or exogenous addition of 8,9-EET phosphorylated the AKT and attenuated Hcy-induced MMP-9 activation. This occurred, in part, by the inhibition of NF-kappa beta nuclear translocation, NF-kappa beta-DNA binding and activation of IK beta alpha. The study unequivocally suggested the pivotal role of EETs in the modulation of Hcy/MMP-9 signal. C1 [Mosha, Karni S.; Sithu, Srinivas D.; Sen, Utpal; Tyagi, Neetu; Kumar, Munish; Hughes, William M., Jr.; Metreveli, Naira; Rosenberger, Dorothea S. E.; Singh, Mahavir; Vacek, Thomas P.; Rodriguez, Walter E.; Ayotunde, Adeagbo; Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40202 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Singh, Mahavir] Potentia Pharmaceut Inc, Res & Dev Div, Louisville, KY USA. RP Tyagi, SC (reprint author), Univ Louisville, Sch Med, Dept Physiol & Biophys, 500 S Preston St,HSC Bldg-A 1115, Louisville, KY 40202 USA. EM s0tyag01@Iouisville.edu FU Intramural NIH HHS [Z01 ES025034-13]; NHLBI NIH HHS [HL-71010, HL-74185, HL-74185 S, HL-88012, R01 HL071010, R01 HL074185, R01 HL088012] NR 35 TC 29 Z9 30 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2008 VL 215 IS 3 BP 771 EP 781 DI 10.1002/jcp.21356 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 298PL UT WOS:000255699500023 PM 18181170 ER PT J AU Hyodo, F Chuang, KH Goloshevsky, AG Sulima, A Griffiths, GL Mitchell, JB Koretsky, AP Krishna, MC AF Hyodo, Fuminori Chuang, Kai-Hsiang Goloshevsky, Artem G. Sulima, Agnieszka Griffiths, Gary L. Mitchell, James B. Koretsky, Alan P. Krishna, Murali C. TI Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood - brain-permeable contrast agent; free radical; MRI; nitroxide; redox ID CEREBRAL-ARTERY OCCLUSION; SPIN-RESONANCE ESR; OXIDATIVE STRESS; ACUTE STROKE; TEMPOL; RAT; VOLUME; DAMAGE; FLOW; MICRODIALYSIS AB Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood - brain barrier (BBB)permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T(1)-mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1- oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9 +/- 0.35 and 3.0 +/- 0.50 mmol/ L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases. C1 [Hyodo, Fuminori; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chuang, Kai-Hsiang; Goloshevsky, Artem G.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [Sulima, Agnieszka; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov RI Koretsky, Alan/C-7940-2015; OI Koretsky, Alan/0000-0002-8085-4756; Chuang, Kai-Hsiang/0000-0002-8356-0657 FU Intramural NIH HHS [Z01 NS003047-01] NR 42 TC 49 Z9 49 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2008 VL 28 IS 6 BP 1165 EP 1174 DI 10.1038/jcbfm.2008.5 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 304NR UT WOS:000256116700009 PM 18270519 ER PT J AU Bauer, B Hartz, AMS Lucking, JR Yang, XD Pollack, GM Miller, DS AF Bauer, Bjoern Hartz, Anika M. S. Lucking, Jonathan R. Yang, Xiaodong Pollack, Gary M. Miller, David S. TI Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GST pi, at the blood-brain barrier SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood - brain barrier; GST pi; Mrp2; PXR; regulation ID PREGNANE-X-RECEPTOR; CONSTITUTIVE-ANDROSTANE RECEPTOR; RESISTANCE PROTEIN-2 MRP2; NECROSIS-FACTOR-ALPHA; GLYCOPROTEIN EXPRESSION; ENDOTHELIAL-CELLS; UP-REGULATION; DRUG; MODULATION; INDUCTION AB Xenobiotic efflux pumps at the blood - brain barrier are critical modulators of central nervous system pharmacotherapy. We previously found expression of the ligand-activated nuclear receptor, pregnane X receptor (PXR), in rat brain capillaries, and showed increased expression and transport activity of the drug efflux transporter, P-glycoprotein, in capillaries exposed to PXR ligands (pregnenolone-16a-carbonitrile (PCN) and dexamethasone) in vitro and in vivo. Here, we show increased protein expression and transport activity of another efflux pump, multidrug resistance-associated protein isoform 2 (Mrp2), in rat brain capillaries after in vitro and in vivo exposure to PCN and dexamethasone. The phase-II drug-metabolizing enzyme, glutathione S-transferase-pi (GST pi), was found to be expressed in brain capillaries, where it colocalized to a large extent with Mrp2 at the endothelial cell luminal plasma membrane. Like Mrp2, GST pi protein expression increased with PXR activation. Colocalization and coordinated upregulation suggest functional coupling of the metabolizing enzyme and efflux transporter. These findings indicate that, as in hepatocytes, brain capillaries possess a regulatory network consisting of nuclear receptors, metabolizing enzymes, and efflux transporters, which modulate blood - brain barrier function. C1 [Bauer, Bjoern; Hartz, Anika M. S.; Lucking, Jonathan R.; Miller, David S.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Bauer, Bjoern] Univ Minnesota, Coll Pharm, Dept Pharmaceut Sci, Duluth, MN 55812 USA. [Hartz, Anika M. S.] Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA. [Yang, Xiaodong; Pollack, Gary M.] Univ N Carolina, Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 73 Z9 73 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2008 VL 28 IS 6 BP 1222 EP 1234 DI 10.1038/jcbfm.2008.16 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 304NR UT WOS:000256116700015 PM 18349876 ER PT J AU Brook, JS Zhang, CS Fagan, P AF Brook, Judith S. Zhang, Chenshu Fagan, Pebbles TI Exposure to Parental Cigarette Smoking and Child Problem Behaviors: A Longitudinal Study SO JOURNAL OF CHILD AND FAMILY STUDIES LA English DT Article DE Parental cigarette smoking; Child-rearing practices; Environmental tobacco smoke; ETS; Effects of parental cigarette smoking on children; Effects of ETS on children; Internalizing behaviors; Externalizing behaviors ID ADOLESCENT DRUG-USE; MATERNAL SMOKING; INITIATION; INVENTORY; MOTHERS; HEALTH AB This study examined exposure to environmental tobacco smoke (ETS), a major public health problem. ETS has been found to be associated with an increased risk of adverse health effects in children. This study utilizes data from a community-based, longitudinal investigation examining the relation between children's exposure to ETS and later internalizing symptoms and externalizing behaviors. Interviews were administered to a representative community sample of participants from two New York State counties in 1983, with subsequent interviews in 1985-1986, 1992, 1997, and 2002-2003 (when the participants' mean age was 32). Data was collected on various personality and behavioral characteristics of the participants, and on internalizing symptoms and externalizing behaviors demonstrated by their children. Results indicated that children's exposure to ETS was associated with an increased risk for both internalizing symptoms and externalizing behaviors. This relationship was maintained despite control on a number of parental psychosocial risk factors ( e. g., demographic variables, personality and behavioral attributes) that have been found to be associated with both parental cigarette smoking and behavior problems among children. These data, which indicate an association between exposure to ETS and internalizing symptoms and externalizing behaviors among children, support public health policies to further restrict children's exposure to ETS. C1 [Brook, Judith S.; Zhang, Chenshu] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Fagan, Pebbles] NCI, Tobacco Control Res Branch, Rockville, MD USA. RP Brook, JS (reprint author), NYU, Sch Med, Dept Psychiat, 215 Lexington Ave,15th Floor, New York, NY 10016 USA. EM judith.brook@med.nyu.edu OI Zhang, Chenshu/0000-0002-3233-3905 FU NCI NIH HHS [R01 CA094845, R01 CA084063]; NIDA NIH HHS [K05 DA000244, R01 DA003188] NR 39 TC 6 Z9 6 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1062-1024 J9 J CHILD FAM STUD JI J. Child Fam. Stud. PD JUN PY 2008 VL 17 IS 3 BP 372 EP 384 DI 10.1007/s10826-007-9147-0 PG 13 WC Family Studies; Psychology, Developmental; Psychiatry SC Family Studies; Psychology; Psychiatry GA 507GF UT WOS:000270839400006 PM 23976837 ER PT J AU Frempong, BA Ricks, M Sen, S Sumner, AE AF Frempong, Barbara A. Ricks, Madia Sen, Sabyasachi Sumner, Anne E. TI Effect of low-dose oral contraceptives on metabolic risk factors in African-American women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; HORMONE REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; INSULIN-RESISTANCE; POSTMENOPAUSAL WOMEN; DIABETES-MELLITUS; FASTING GLUCOSE; UNITED-STATES; MARKERS AB Context: The effect of oral contraceptive pill (OCP) use on cardiovascular risk in African-American women is unknown. Objective: Our objective was to examine in African-American women the effect of OCP use on insulin resistance, glucose intolerance, and triglycerides (TGs). Design: This was a cross-sectional study. Setting: The study was conducted at the National Institutes of Health Clinical Research Center. Participants: A total of 104 healthy nondiabetic African-American women [21 OCP users, 83 controls, age mean +/- SD, 34.7 +/- 7.6 yr, body mass index (BMI) 31 +/- 8.4 kg/m(2)] was included in the study. Interventions: Subjects had oral glucose tolerance tests, insulin-modified frequently sampled iv glucose tolerance tests, and fasting lipid profiles. Insulin resistance was determined by the insulin sensitivity index (S-I). Main Outcome Measures: Insulin resistance, glucose tolerance status, and TG levels were determined. Results: Fasting glucose did not differ between OCP users and controls (P = 0.27). In contrast, compared with controls, 2-h glucose (135 +/- 23 vs. 120 +/- 25 mg/dl; P = 0.01) and fasting TGs (73 +/- 31 vs. 57 +/- 27 mg/dl; P = 0.02) were higher in OCP users. OCP users tended to be more insulin resistant than controls (SI: 2.51 +/- 2.01 vs. 3.46 +/- 2.09; P = 0.09). Multiple regression analysis revealed that BMI, age, and OCP use were significant determinants of 2-h glucose (adjusted R-2 = 0.37; P < 0.001) and TG levels (adjusted R-2 = 0.21; P < 0.001). As BMI was a determinant of both 2-h glucose and TGs, participants were divided into nonobese and obese groups, and the analyses repeated. Among the nonobese women, the OCP users were more insulin resistant (S-I: 2.91 +/- 1.58 vs. 4.35 +/- 1.88; P = 0.03) and had a higher prevalence of glucose intolerance than controls (odds ratio 5.7; 95% confidence interval 1.4-24; P = 0.01). Conclusion: In African-American women, OCP use is associated with an increase in markers of cardiovascular risk manifested by increased insulin resistance, glucose intolerance, and elevated TGs. C1 [Frempong, Barbara A.; Ricks, Madia; Sen, Sabyasachi; Sumner, Anne E.] NIDDKD, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Sumner, AE (reprint author), NIDDKD, NIH, Clin Endocrinol Branch, 9000 Rockville Pike,Bldg 10-CRC,Room 6-5940,MSC 1, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov FU Intramural NIH HHS NR 42 TC 15 Z9 15 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 JUN PY 2008 VL 93 IS 6 BP 2097 EP 2103 DI 10.1210/jc.2007-2599 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900011 PM 18334585 ER PT J AU Wooten, N Bakalov, VK Hill, S Bondy, CA AF Wooten, Nicole Bakalov, Vladimir K. Hill, Suvimol Bondy, Carolyn A. TI Reduced abdominal adiposity and improved glucose tolerance in growth hormone-treated girls with Turner syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED INSULIN-SECRETION; CARBOHYDRATE-METABOLISM; BODY-COMPOSITION; GONADAL DYSGENESIS; DIABETES-MELLITUS; LIPID-METABOLISM; FAT DISTRIBUTION; RISK-FACTORS; GH TREATMENT; DISCONTINUATION AB Background: Individuals with Turner syndrome (TS) are at increased risk for impaired glucose tolerance and diabetes mellitus. It is unknown whether pharmacological GH treatment commonly used to treat short stature in TS alters this risk. Objective: Our objective was to compare adiposity and glucose tolerance in GH-treated vs. untreated girls with TS. Methods: In a cross sectional study, GH-treated girls with TS (n = 76; age 13.6 +/- 3.7 yr) were compared to girls with TS that never received GH (n = 26; age 13.8 +/- 3.5 yr). Protocol studies took place in the NIH Clinical Research Center from 2001-2006 and included oral glucose tolerance tests, body composition analysis by dual-energy x-ray absorptiometry, and abdominal fat quantification by magnetic resonance imaging. GH was not given during testing. Results: Total body fat (35 +/- 8 vs. 28 +/- 8%, P < 0.0001), sc abdominal fat (183 vs. 100 ml, P = 0.001), and intraabdominal fat (50 vs. 33 ml, P < 0.0001) were significantly greater in untreated girls. Fasting glucose and insulin were similar, but the response to oral glucose was significantly impaired in the untreated group (28 vs. 7% with impaired glucose tolerance, P = 0.006). A specific excess of visceral fat and insulin resistance was apparent only in postpubertal girls that had never received GH. GH-treated girls demonstrated lower adiposity compared with untreated girls for an average of 2 yr after discontinuation of GH. Conclusions: Abdominal adiposity is significantly lower and glucose tolerance significantly better in GH-treated vs. untreated girls with TS, suggesting that beneficial effects upon body composition and regional fat deposition outweigh transient insulin antagonism associated with GH administration. C1 [Wooten, Nicole; Bakalov, Vladimir K.; Bondy, Carolyn A.] NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Hill, Suvimol] NIH, Clin Ctr Radiol, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 30 TC 24 Z9 25 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 JUN PY 2008 VL 93 IS 6 BP 2109 EP 2114 DI 10.1210/jc.2007-2266 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900013 PM 18349057 ER PT J AU Black, DM Bouxsein, ML Palermo, L McGowan, JA Newitt, DC Rosen, E Majumdar, S Rosen, CJ AF Black, Dennis M. Bouxsein, Mary L. Palermo, Lisa McGowan, Joan A. Newitt, David C. Rosen, Eyal Majumdar, Sharmila Rosen, Clifford J. CA POWR Grp TI Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID-HORMONE 1-34; POSTMENOPAUSAL OSTEOPOROSIS; VERTEBRAL FRACTURE; TRABECULAR BONE; WOMEN; ALENDRONATE; TERIPARATIDE; THERAPY; COMBINATION; RALOXIFENE AB Context: Daily PTH administration increases bone mineral density (BMD) and reduces fracture risk. However, cost and compliance significantly limit clinical use. Objective: Our objective was to determine whether less frequent PTH administration increases lumbar spine BMD. Participants, Design, and Setting: Fifty postmenopausal women ages 45-70 yr with femoral neck BMD T-score between -1.0 and -2.0 participated in a double-blind, randomized, placebo-controlled trial at St. Joseph Hospital, Bangor, ME. Intervention: Subjects received sc injections of daily PTH(1-84) (100 mu g) or placebo for 1 month, followed by weekly injections (PTH or placebo) for 11 months. Outcomes: Change in lumbar spine dual-energy x-ray absorptiometry areal BMD (primary) was assessed. Secondary outcomes included volumetric BMD at spine and hip by quantitative computed tomography, trabecular bone microarchitecture by magnetic resonance imaging of distal radius, and biochemical bone turnover markers. Results: At 12 months, lumbar spine areal BMD increased 2.1% in PTH-treated women compared with placebo (P = 0.03). Vertebral trabecular volumetric BMD increased 3.8% in PTH-treated women compared with placebo group (P = 0.08). PTH-treated women also had higher distal radial trabecular bone volume, number, and thickness compared with placebo-treated women (P < 0.04). After 1 month of daily PTH, N-terminal propeptide of type I collagen (P1NP) was markedly increased compared with placebo (P < 0.0001), and a difference persisted, although lessened, throughout the study. Bone resorption indices were unchanged in PTH-treated women and were reduced in the placebo group. Conclusion: Once-weekly PTH after 1 month of daily treatment increases spine BMD, radial trabecular bone, and bone formation markers in postmenopausal women. These results suggest that less frequent alternatives to daily PTH dosing for 2 yr could be effective. Additional studies are required to define the optimal frequency of PTH administration. C1 [Black, Dennis M.; Palermo, Lisa] Univ Calif San Francisco, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Black, Dennis M.; Palermo, Lisa] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94107 USA. [Black, Dennis M.; Palermo, Lisa] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94107 USA. [Newitt, David C.; Majumdar, Sharmila] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94107 USA. [Bouxsein, Mary L.; Rosen, Eyal] Beth Israel Deaconess Med Ctr, Dept Orthoped, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. [McGowan, Joan A.] NIAMSD, NIH, Bethesda, MD 20894 USA. [Rosen, Clifford J.] Univ Maine, St Joseph Hosp, Maine Ctr Osteoporosis Res, Bangor, ME 04401 USA. RP Black, DM (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA. EM dblack@psg.ucsf.edu FU NIAMS NIH HHS [N01 AR 32268, N01AR32268] NR 18 TC 26 Z9 26 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2008 VL 93 IS 6 BP 2166 EP 2172 DI 10.1210/jc.2007-2781 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900021 PM 18349061 ER PT J AU Celi, FS Coppotelli, G Chidakel, A Kelly, M Brillante, BA Shawker, T Cherman, N Feuillan, PP Collins, MT AF Celi, Francesco S. Coppotelli, Giuseppe Chidakel, Aaron Kelly, Marilyn Brillante, Beth A. Shawker, Thomas Cherman, Natasha Feuillan, Penelope P. Collins, Michael T. TI The role of type 1 and type 2 5 '-deiodinase in the pathophysiology of the 3,5,3 '-triiodothyronine toxicosis of McCune-Albright syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THYROID-HORMONE ACTIVATION; STIMULATORY G-PROTEIN; IODOTHYRONINE DEIODINASE; FIBROUS DYSPLASIA; GRAVES-DISEASE; ALPHA-SUBUNIT; RAT-KIDNEY; GENE; THYROXINE; MUTATIONS AB Context: McCune-Albright syndrome (MAS) is caused by mutations in GNAS (most often R201C or R201H) leading to constitutive cAMP signaling and multiple endocrine dysfunctions, including morphological and functional thyroid involvement. Objective: The objective of the study was to characterize the clinical and molecular features of the MAS-associated thyroid disease in a large cohort of patients. Design: This was a retrospective analysis. Setting: The study was conducted at the National Institutes of Health Clinical Center. Patients: The study included 100 consecutive MAS patients. Interventions: There were no interventions. Main Outcome Measure: Functional and morphological evaluation of the thyroid was measured. Ex vivo experiments were performed on MAS thyroid samples to study the effects of the GNAS mutations on the 5'-deiodinases. Reconstitution experiments in HEK-293 cells were performed to study the effects of GNAS mutations on the type-2 5'-deiodinase. Results: Fifty-four patients had abnormal thyroid ultrasound findings. This group, compared with patients without abnormal findings, had higher T3 to T4 ratio, indicating an elevated 5'-deiodinase activity. Thyroid samples from MAS subjects, compared with normal tissue, showed a significant increase in both type 1 (D1) and type 2 (D2) 5'-deiodinase activity (D1 control 5.9 +/- 4.5 vs. MAS 41.7 +/- 26.8 fmol/min.mg, P < 0.001; D2 control 28.3 +/- 13.8 vs. MAS 153.1 +/- 43.7 fmol/min.mg, P < 0.001). Compared with cells transfected with the wild-type R201 allele, the basal transcriptional activity of the D2 promoter was significantly increased in both mutants (C and H) (R 10733 +/- 2855, vs. C 18548 +/- 4514, vs. H 19032 +/- 4410 RLU +/- SD, P < 0.001). Conclusion: Thyroid pathology is a common occurrence in MAS. Consistent with the molecular etiology of the disease, the shift in T3 to T4 ratio is at least in part secondary to a cAMP-mediated intrathyroidal activation of D2 and to elevated D1 activity. C1 [Celi, Francesco S.; Coppotelli, Giuseppe; Chidakel, Aaron] NIDDKD, Clin Endocrinol Branch, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacila Res, Skeletal Clin Studies Unit, Craniofacila & Skeletal Dis Branch, Radiol Dept,NIH, Bethesda, MD 20892 USA. [Feuillan, Penelope P.] NHGRI, Hatfield Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Celi, FS (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Clin Res Ctr, Bldg 10,Room 6-3940,10 Ctr Dr MSC 1613, Bethesda, MD 20892 USA. EM fc93a@nih.gov OI Chidakel, Aaron/0000-0002-0854-7348 FU Intramural NIH HHS [Z01 DK075001-04] NR 36 TC 15 Z9 16 U1 1 U2 3 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 JUN PY 2008 VL 93 IS 6 BP 2383 EP 2389 DI 10.1210/jc.2007-2237 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900053 PM 18349068 ER PT J AU Klatt, NR Villinger, F Bostik, P Gordon, SN Pereira, L Engram, JC Mayne, A Dunham, RM Lawson, B Ratcliffe, SJ Sodora, DL Else, J Reimann, K Staprans, SI Haase, AT Estes, JD Silvestri, G Ansari, AA AF Klatt, Nichole R. Villinger, Francois Bostik, Pavel Gordon, Shari N. Pereira, Lara Engram, Jessica C. Mayne, Ann Dunham, Richard M. Lawson, Benton Ratcliffe, Sarah J. Sodora, Donald L. Else, James Reimann, Keith Staprans, Silvija I. Haase, Ashley T. Estes, Jacob D. Silvestri, Guido Ansari, Aftab A. TI Availability of activated CD4(+) T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW-TRANSPLANTATION; RHESUS MACAQUES; AIDS PATHOGENESIS; VIRAL DYNAMICS; HIV-INFECTION; IMMUNE RECONSTITUTION; CD8(+) LYMPHOCYTES; DEPLETION; REPLICATION AB Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4(+) T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4(+) T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14(+) monocytes was observed. Importantly, CD4(+) T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30-45, coincident with an increased fraction of proliferating and activated CD4(+) T cells. Throughout the study, virus replication correlated with the level of proliferating CD4(+) T cells. CD4(+) T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8(+) T cells. Our results suggest that the availability of activated CD4(+) T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs. C1 [Klatt, Nichole R.; Gordon, Shari N.; Engram, Jessica C.; Dunham, Richard M.; Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Villinger, Francois; Bostik, Pavel; Pereira, Lara; Mayne, Ann; Ansari, Aftab A.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Klatt, Nichole R.; Villinger, Francois; Gordon, Shari N.; Dunham, Richard M.; Lawson, Benton; Else, James; Silvestri, Guido; Ansari, Aftab A.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Ratcliffe, Sarah J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sodora, Donald L.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Sodora, Donald L.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Reimann, Keith] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Staprans, Silvija I.] Merck Vaccines, West Point, PA USA. [Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Estes, Jacob D.] NCI, Sci Applicat Int Corp, AIDS & Canc Virus Program, Frederick, MD 21701 USA. RP Silvestri, G (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 705 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. EM gsilvest@mail.med.upenn.edu; pathaaa@emory.edu RI Dunham, Richard/B-2012-2009; OI Dunham, Richard/0000-0003-4542-2330; Ratcliffe, Sarah/0000-0002-6644-8284 FU NCRR NIH HHS [RR-00165, P51 RR000165, R24 RR016001, R24 RR016988, R24RR16988, RR016001]; NHLBI NIH HHS [R01 HL075766, R01-HL-75766]; NIAID NIH HHS [AI040101, R01 AI027057, R01 AI040101, R01 AI066998, R01-AI27057, R01-AI66998, R21 AI060451, R21-AI060451] NR 50 TC 60 Z9 60 U1 0 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 JUN PY 2008 VL 118 IS 6 BP 2039 EP 2049 DI 10.1172/JCI33814 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 309FC UT WOS:000256445100010 PM 18497876 ER PT J AU Olive, M Mellad, JA Beltran, LE Ma, MC Cimato, T Noguchi, AC San, H Childs, R Kovacic, JC Boehm, M AF Olive, Michelle Mellad, Jason A. Beltran, Leilani E. Ma, Mingchao Cimato, Thomas Noguchi, Audrey C. San, Hong Childs, Richard Kovacic, Jason C. Boehm, Manfred TI p21(Cip1) modulates arterial wound repair through the stromal cell-derived factor-1/CXCR4 axis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VASCULAR SMOOTH-MUSCLE; HEMATOPOIETIC PROGENITOR CELLS; DEPENDENT KINASE INHIBITORS; CHEMOKINE RECEPTOR CXCR4; SIROLIMUS-ELUTING STENTS; NEOINTIMA FORMATION; CDK INHIBITORS; IN-VIVO; EXPRESSION; P21 AB Cyclin-dependent kinase inhibitors, including p21(Cip1), are implicated in cell turnover and are active players in cardiovascular wound repair. Here, we show that p21(Cip1) orchestrates the complex interactions between local vascular and circulating immune cells during vascular wound repair. In response to femoral artery mechanical injury, mice with homozygous deletion of p21(Cip1) displayed accelerated proliferation of VSMCs and increased immune cell infiltration. BM transplantation experiments indicated that local p21(Cip1) plays a pivotal role in restraining excessive proliferation during vascular wound repair. Increased local vascular stromal cell-derived factor-1 (SDF-1) levels were observed after femoral artery injury in p21(+/+) and p21(-/-) mice, although this was significantly greater in p21(-/-) animals. In addition, disruption of SDF-1/CXCR4 signaling inhibited the proliferative response during vascular remodeling in both p21(+/+) and p21(-/-) mice. We provide evidence that the JAK/STAT signaling pathway is an important regulator of vascular SDF-1 levels and that P21(Cip1) inhibits STAT3 binding to the STAT-binding site within the murine SDF-1 promoter. Collectively, these results suggest that p21(Cip1) activity is essential for the regulation of cell, proliferation and inflammation after arterial injury in local vascular cells and that the SDF-1/CXCR4 signaling system is a key mediator of vascular proliferation in response to injury. C1 [Mellad, Jason A.; Beltran, Leilani E.; Ma, Mingchao; Cimato, Thomas; Noguchi, Audrey C.; Kovacic, Jason C.; Boehm, Manfred] NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20817 USA. [Childs, Richard] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. [Olive, Michelle; San, Hong] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Boehm, M (reprint author), NHLBI, NIH, Cardiovasc Branch, Bldg 10-CRC,Room 5-3132, Bethesda, MD 20817 USA. EM boehmm@nhlbi.nih.gov OI Cimato, Thomas/0000-0001-9230-4463 FU Intramural NIH HHS NR 66 TC 37 Z9 40 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2008 VL 118 IS 6 BP 2050 EP 2061 DI 10.1172/JCI31244 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 309FC UT WOS:000256445100011 PM 18464929 ER PT J AU Li, HW Armando, I Yu, PY Escano, C Mueller, SC Asico, L Pascua, A Lu, QS Wang, XY Villar, VM Jones, JE Wang, Z Periasamy, A Lau, YS Soares-da-Silva, P Creswell, K Guillemette, G Sibley, DR Eisner, G Felder, RA Jose, PA AF Li, Hewang Armando, Ines Yu, Peiying Escano, Crisanto Mueller, Susette C. Asico, Laureano Pascua, Annabelle Lu, Quansheng Wang, Xiaoyan Villar, Van Anthony M. Jones, John E. Wang, Zheng Periasamy, Ammasi Lau, Yuen-Sum Soares-da-Silva, Patricio Creswell, Karen Guillemette, Gaetan Sibley, David R. Eisner, Gilbert Felder, Robin A. Jose, Pedro A. TI Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID D-5 DOPAMINE-RECEPTORS; RENIN-ANGIOTENSIN SYSTEM; N-LINKED GLYCOSYLATION; HUMAN AT(1) RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; ESSENTIAL-HYPERTENSION; PROTEIN-DEGRADATION; PRESSURE REGULATION; PLASMA-MEMBRANE; DOWN-REGULATION AB Hypertension is a multigenic disorder in which abnormal counterregulation between dopamine and Ang II plays a role. Recent studies suggest that this counterregulation results, at least in part, from regulation of the expression of both the antihypertensive dopamine 5 receptor (D(5)R) and the prohypertensive Ang II type 1 receptor (AT(1)R). in this report, we investigated the in vivo and in vitro interaction between these GPCRs. Disruption of the gene encoding D(5)R in mice increased both blood pressure and AT(1)R protein expression, and the increase in blood pressure was reversed by AT(1)R blockade. Activation of D(5)R increased the degradation of glycosylated AT(1)R in proteasomes in HEK cells and human renal proximal tubule cells heterologously and endogenously expressing human AT(1)R and D(5)R. Confocal microscopy, Forster/fluorescence resonance energy transfer microscopy, and fluorescence lifetime imaging microscopy revealed that activation of D(5)R initiated ubiquitination of the glycosylated AT,R at the plasma membrane. The regulated degradation of AT(1)R via a ubiquitin/proteasome pathway by activation of D(5)R provides what we believe to be a novel mechanism whereby blood pressure can be regulated by the interaction of 2 counterregulatory GPCRs. Our results therefore suggest that treatments for hypertension might be optimized by designing compounds that can target the AT(1)R and the D(5)R. C1 [Li, Hewang; Armando, Ines; Yu, Peiying; Escano, Crisanto; Asico, Laureano; Pascua, Annabelle; Lu, Quansheng; Wang, Xiaoyan; Villar, Van Anthony M.; Jones, John E.; Wang, Zheng; Jose, Pedro A.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Pediat, Washington, DC 20007 USA. [Mueller, Susette C.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Periasamy, Ammasi] Univ Virginia, Keck Ctr Cellular Imaging, Charlottesville, VA USA. [Periasamy, Ammasi] Univ Virginia, Dept Biol, Charlottesville, VA USA. [Lau, Yuen-Sum] Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA. [Soares-da-Silva, Patricio] Fac Med Porto, Inst Pharmacol & Therapeut, Oporto, Portugal. [Creswell, Karen] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Flow Cytometry & Cell Sorting Ctr, Washington, DC 20007 USA. [Guillemette, Gaetan] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Pharmacol, Sherbrooke, PQ J1K 2R1, Canada. [Sibley, David R.] Natl Inst Neurol Disorders & Stroke, NIH, Mol Neuropharmacol Sect, Bethesda, MD USA. [Eisner, Gilbert] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Felder, Robin A.] Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA USA. RP Jose, PA (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Pediat, Washington, DC 20007 USA. EM pjose01@georgetown.edu RI Periasamy, Ammasi/B-1279-2010; Soares-da-Silva, Patricio/A-6704-2015 OI Soares-da-Silva, Patricio/0000-0002-2446-5078 FU NCI NIH HHS [CA51008, P30 CA051008]; NCRR NIH HHS [RR15768-01]; NHLBI NIH HHS [HL23081, HL074940, HL68686, P01 HL068686, P01 HL074940, R01 HL023081, R37 HL023081]; NIDDK NIH HHS [DK39308, DK52612, P50 DK052612, R01 DK039308] NR 57 TC 52 Z9 56 U1 0 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 JUN PY 2008 VL 118 IS 6 BP 2180 EP 2189 DI 10.1172/JCI33637 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 309FC UT WOS:000256445100022 PM 18464932 ER PT J AU Tan, HY Nicodemus, KK Chen, Q Li, Z Brooke, JK Honea, R Kolachana, BS Straub, RE Meyer-Lindenberg, A Sei, Y Mattay, VS Callicott, JH Weinberger, DR AF Tan, Hao-Yang Nicodemus, Kristin K. Chen, Qiang Li, Zhen Brooke, Jennifer K. Honea, Robyn Kolachana, Bhaskar S. Straub, Richard E. Meyer-Lindenberg, Andreas Sei, Yoshitasu Mattay, Venkata S. Callicott, Joseph H. Weinberger, Daniel R. TI Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; GENERAL FLUID INTELLIGENCE; WORKING-MEMORY; HUMAN BRAIN; NEUROPSYCHOLOGICAL DYSFUNCTION; PARKINSONS-DISEASE; COGNITIVE DEFICITS; MIDBRAIN DOPAMINE; SIGNALING CASCADE; RECEPTOR ACTIONS AB AKT1-dependent molecular pathways control diverse aspects of cellular development and adaptation, including interactions with neuronal dopaminergic signaling. if AKT1 has an impact on dopaminergic signaling, then genetic variation in AKT1 would be associated with brain phenotypes related to cortical dopaminergic function. Here, we provide evidence that a coding variation in AKT1 that affects protein expression in human B lymphoblasts influenced several brain measures related to dopaminergic function. Cognitive performance linked to frontostriatal circuitry, prefrontal. physiology during executive function, and frontostriatal gray-matter volume on MRI were altered in subjects with the AKT1 variation. Moreover, on neuroimaging measures with a main effect of the AKT1 genotype, there was significant epistasis with a functional polymorphism (Val158Met) in catechol-O-methyltransferase [COMT], a gene that indexes cortical synaptic dopamine. This genetic interaction was consistent with the putative role of AKT1 in dopaminergic signaling. Supportive of an earlier tentative association of AKT1 with schizophrenia, we also found that this AKT1 variant was associated with risk for schizophrenia. These data implicate AKT1 in modulating human prefrontal-striatal structure and function and suggest that the mechanism of this effect may be coupled to dopaminergic signaling and relevant to the expression of psychosis. C1 [Tan, Hao-Yang; Nicodemus, Kristin K.; Chen, Qiang; Li, Zhen; Brooke, Jennifer K.; Honea, Robyn; Kolachana, Bhaskar S.; Straub, Richard E.; Meyer-Lindenberg, Andreas; Sei, Yoshitasu; Mattay, Venkata S.; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, NIH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,Div Intramural R, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, NIH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,Div Intramural R, 10 Center Dr,Room 4S-235, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011 OI Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 77 TC 114 Z9 116 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2008 VL 118 IS 6 BP 2200 EP 2208 DI 10.1172/JCI3472S PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 309FC UT WOS:000256445100024 PM 18497887 ER PT J AU Francesconi, A Kasai, M Harrington, SM Beveridge, MG Petraitiene, R Petraitis, V Schaufele, RL Walsh, TJ AF Francesconi, Andrea Kasai, Miki Harrington, Susan M. Beveridge, Mara G. Petraitiene, Ruta Petraitis, Vidmantas Schaufele, Robert L. Walsh, Thomas J. TI Automated and manual methods of DNA extraction for Aspergillus fumigatus and Rhizopus oryzae analyzed by quantitative real-time PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; CELL TRANSPLANT RECIPIENTS; POLYMERASE-CHAIN-REACTION; HEMATOPOIETIC STEM-CELL; BRONCHOALVEOLAR LAVAGE; FUNGAL DNA; FILAMENTOUS FUNGI; GENOMIC DNA; DIAGNOSIS; INFECTIONS AB Quantitative real-time PCR (qPCR) may improve the detection of fungal pathogens. Extraction of DNA from fungal pathogens is fundamental to optimization of qPCR; however, the loss of fungal DNA during the extraction process is a major limitation to molecular diagnostic tools for pathogenic fungi. We therefore studied representative automated and manual extraction methods for Aspergillus fumigatus and Rhizopus oryzae. Both were analyzed by qPCR for their ability to extract DNA from propagules and germinated hyphal elements (GHE). The limit of detection of A. fumigatus and R. oryzae GHE in bronchoalveolar lavage (BAL) fluid with either extraction method was 1 GHE/ml. Both methods efficiently extracted DNA from A. fumigatus, with a limit of detection of 1 x 10(2) conidia. Extraction of R. oryzae by the manual method resulted in a limit of detection of 1 x 10(3) sporangiospores. However, extraction with the automated method resulted in a limit of detection of 1 x 10(1) sporangiospores. The amount of time to process 24 samples by the automated method was 2.5 h prior to transferring for automation, 1.3 h of automation, and 10 min postautomation, resulting in a total time of 4 h. The total time required for the manual method was 5.25 h. The automated and manual methods were similar in sensitivity for DNA extraction from A. fumigatus conidia and GHE. For R. oryzae, the automated method was more sensitive for DNA extraction of sporangiospores, while the manual method was more sensitive for GHE in BAL fluid. C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Harrington, Susan M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Petraitiene, Ruta; Petraitis, Vidmantas] SAIC Frederick Inc, LASP, Frederick, MD USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10-CRC,Rm 1-5740, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 38 TC 25 Z9 27 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2008 VL 46 IS 6 BP 1978 EP 1984 DI 10.1128/JCM.02246-07 PG 7 WC Microbiology SC Microbiology GA 341DX UT WOS:000258695500015 PM 18353931 ER PT J AU Brenner, RP Drislane, FW Ebersole, JS Grigg-Damberger, M Hallett, M Herman, ST Hirsch, LJ Husain, AM Kaplan, P Legatt, AD Nordli, DR Parry, GJ Ross, MA Schomer, DL So, EL Sumner, AJ Tatum, WO AF Brenner, Richard P. Drislane, Frank W. Ebersole, John S. Grigg-Damberger, Madeleine Hallett, Mark Herman, Susan T. Hirsch, Lawrence J. Husain, Aatif M. Kaplan, Peter Legatt, Alan D. Nordli, Douglas R., Jr. Parry, Gareth J. Ross, Mark A. Schomer, Donald L. So, Elson Lee Sumner, Austin J. Tatum, William O. TI Guideline twelve: Guidelines for long-term monitoring for epilepsy SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article C1 [Brenner, Richard P.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Drislane, Frank W.] Beth Israel Deaconess Med Ctr, Newton, MA USA. [Ebersole, John S.] Univ Chicago, Chicago, IL 60637 USA. [Grigg-Damberger, Madeleine] Univ New Mexico, Albuquerque, NM 87131 USA. [Hallett, Mark] NIH, Bethesda, MD 20892 USA. [Herman, Susan T.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Hirsch, Lawrence J.] Columbia Univ, New York, NY USA. [Husain, Aatif M.] Duke Univ, Med Ctr, Durham, NC USA. [Kaplan, Peter] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Legatt, Alan D.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Nordli, Douglas R., Jr.] Childrens Epilepsy Ctr, Chicago, IL USA. [Parry, Gareth J.] Univ Minneapolis, Minneapolis, MN USA. [Ross, Mark A.] Mayo Clin, Scottsdale, AZ USA. [Schomer, Donald L.] Beth Israel Deaconess Med Ctr, Hingham, MA USA. [So, Elson Lee] Mayo Clin, Rochester, MN USA. [Sumner, Austin J.] LSU Sch Med, New Orleans, LA USA. [Tatum, William O.] Univ S Florida, Tampa, FL USA. RP Brenner, RP (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2008 VL 25 IS 3 BP 170 EP 180 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 310TZ UT WOS:000256554600008 ER PT J AU Wilson, WH Dunleavy, K Pittaluga, S Hegde, U Grant, N Steinberg, SM Raffeld, M Gutierrez, M Chabner, BA Staudt, L Jaffe, ES Janik, JE AF Wilson, Wyndham H. Dunleavy, Kieron Pittaluga, Stefania Hegde, Upendra Grant, Nicole Steinberg, Seth M. Raffeld, Mark Gutierrez, Martin Chabner, Bruce A. Staudt, Louis Jaffe, Elaine S. Janik, John E. TI Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-Cell lymphoma with analysis of germinal center and post-germinal center biomarkers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMAS; CHEMOTHERAPY PLUS RITUXIMAB; R-CHOP; ELDERLY-PATIENTS; BCL-2-ASSOCIATED RESISTANCE; PROGNOSTIC-SIGNIFICANCE; RESPONSE CRITERIA; DRUG-RESISTANCE; EXPRESSION; BCL-6 AB Purpose To assess the clinical outcome and the influence of biomarkers associated with apoptosis inhibition (Bcl- 2), tumor proliferation (MIB-1), and cellular differentiation on the outcome with dose-adjusted (DA) EPOCH ( etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) plus rituximab ( R) infusional therapy in diffuse large B-cell lymphoma (DLBCL) with analysis of germinal center B-cell (GCB) and post-GCB subtypes by immunohistochemistry. Patients and Methods Phase II study of 72 patients with untreated de novo DLBCL who were at least 18 years of age and stage II or higher. Radiation consolidation was not permitted. Results Patients had a median age of 50 years ( range, 19 to 85) and 40% had a high-intermediate or high International Prognostic Index ( IPI). At 5 years, progression-free survival (PFS) and overall survival ( OS) were 79% and 80%, respectively, with a median potential follow-up of 54 months. PFS was 91%, 90%, 67%, and 47%, and OS was 100%, 90%, 74%, and 37%, for 0 to 1, 2, 3, and 4 to 5 IPI factors, respectively, at 5 years. The Bcl- 2 and MIB-1 biomarkers were not associated with PFS or OS. Based on DA-EPOCH historical controls, rituximab only benefited Bcl- 2 positive tumors. Bcl- 6 expression was associated with higher PFS whereas GCB exhibited a marginally significant higher PFS compared with post-GCB DLBCL. Conclusion DA-EPOCH-R outcome was not affected by tumor proliferation and rituximab appeared to overcome the adverse effect of Bcl-2. Bcl-6 may identify a biologic program associated with a superior outcome. Overall, DA-EPOCH-R shows promising outcome in low and intermediate IPI groups. A molecular model of treatment outcome with rituximab and chemotherapy is presented. C1 Ctr Canc Res, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Connecticut, Hartford, CT 06112 USA. RP Wilson, WH (reprint author), NCI, Metab Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov FU Intramural NIH HHS [Z01 SC006741-13] NR 49 TC 139 Z9 154 U1 1 U2 5 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 JUN 1 PY 2008 VL 26 IS 16 BP 2717 EP 2724 DI 10.1200/JCO.2007.13.1391 PG 8 WC Oncology SC Oncology GA 305XC UT WOS:000256210100020 PM 18378569 ER PT J AU Penzak, SR Busse, KH Robertson, SM Formentini, E Alfaro, RM Davey, RT AF Penzak, Scott R. Busse, Kristin H. Robertson, Sarah M. Formentini, Elizabeth Alfaro, Raul M. Davey, Richard T., Jr. TI Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE midazolam; Ginkgo biloba extract; drug interactions; CYP3A ID CYTOCHROME-P450 3A ACTIVITY; CYP3A; PROBE; ADULTS AB Midazolam is a common probe used to predict CYP3A activity, but multiple blood samples are necessary to determine midazolam's area under the concentration-time curve (AUC). As such, single sampling strategies have been examined. The purpose of this study was to assess the ability of single midazolam concentrations to predict midazolam AUC in the presence and absence of CYP3A modulation by Ginkgo biloba extract (GBE). Subjects received oral midazolam 8 mg before and after 28 days of GBE administration. Postdose blood samples were collected during both study periods and midazolam AUC determined. Linear regression was used to generate measures of predictive performance for each midazolam concentration. The geometric mean ratio (90% confidence intervals) of midazolam AUC(0-infinity) post-GBE/AUC(0-infinity) pre-GBE was 0.66 (0.49-0.84) (P = .03). Before and after GBE administration, optimal midazolam sampling times were identified at 3.5 to 5 hours and 2 to 3 hours, respectively. Single midazolam concentrations between 2 and 5 hours correctly predicted the reduction in midazolam AUC following GBE exposure, but confidence intervals were generally wide. Intersubject variability in CYP3A activity (either inherent or from drug administration) alters the prediction of optimal midazolam sampling times; therefore, midazolam AUC is preferred for assessing CYP3A activity in drug-drug interaction studies. C1 [Penzak, Scott R.] NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Formentini, Elizabeth] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Davey, Richard T., Jr.] NIAID, NIH, Bethesda, MD 20892 USA. RP Penzak, SR (reprint author), NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bldg 10,Room 1N 257, Bethesda, MD 20892 USA. EM spenzak@mail.cc.nih.gov FU Intramural NIH HHS [Z01 CL005098-03] NR 15 TC 22 Z9 23 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 2008 VL 48 IS 6 BP 671 EP 680 DI 10.1177/0091270008317305 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305CZ UT WOS:000256156700002 PM 18420532 ER PT J AU Machado-Vieira, R Salvadore, G Luckenbaugh, DA Manji, HK Zarate, CA AF Machado-Vieira, Rodrigo Salvadore, Giacomo Luckenbaugh, David A. Manji, Husseini K. Zarate, Carlos A. TI Rapid onset of antidepressant action: A new paradigm in the research and treatment of major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID THYROTROPIN-RELEASING-HORMONE; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION; PARTIAL SLEEP-DEPRIVATION; CELLULAR PLASTICITY CASCADES; GENE PROMOTER POLYMORPHISM; HIPPOCAMPAL VOLUME LOSS; DEEP BRAIN-STIMULATION; TRUE DRUG RESPONSE; ELECTROCONVULSIVE-THERAPY AB Objective: Current therapeutics of depression are similar in their time to antidepressant action and often take weeks to months to achieve response and remission, which commonly results in considerable morbidity and disruption in personal, professional, family, and social life, as well as risk for suicidal behavior. Thus, treatment strategies presenting a rapid improvement of depressive symptoms-within hours or even a few days-and whose effects are sustained would have an enormous impact on public health. This article reviews the published data related to different aspects of rapid improvement of depressive symptoms. Data Sources: Literature for this review was obtained through a search of the MEDLINE database (1966-2007) using the following keywords and phrases: rapid response, antidepressant, time to, glutamate, sleep, therapeutics, latency, and depression. The data obtained were organized according to the following topics: clinical relevance and time course of antidepressant action, interventions showing evidence of rapid response and its potential neurobiological basis, and new technologies for better understanding rapid antidepressant actions. Data Synthesis: A limited number of prospective studies evaluating rapid antidepressant actions have been conducted. Currently, only a few interventions have been shown to produce antidepressant response in hours or a few days. The neurobiological basis of these rapid antidepressant actions is only now being deciphered. Conclusions: Certain experimental treatments can produce antidepressant response in a much shorter period of time than existing medications. Understanding the molecular basis of these experimental interventions is likely to lead to the development of improved therapeutics rather than simply furthering our knowledge of current standard antidepressants. C1 [Machado-Vieira, Rodrigo; Salvadore, Giacomo; Luckenbaugh, David A.; Manji, Husseini K.; Zarate, Carlos A.] NIMH, Mark O Hatfield Clin Res Ctr, Dept Hlth & Human Serv, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Mark O Hatfield Clin Res Ctr, Dept Hlth & Human Serv, Mood & Anxiety Disorders Program, 10 Ctr Dr,Unit 7SE,Rm 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Intramural NIH HHS [Z01 MH002857-03, Z01 MH002828-05, Z01 MH002853-03] NR 148 TC 88 Z9 92 U1 2 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2008 VL 69 IS 6 BP 946 EP 958 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 318LI UT WOS:000257092800010 PM 18435563 ER PT J AU Schmidt, PJ Steinberg, EM Rubinow, DR AF Schmidt, Peter J. Steinberg, Emma M. Rubinow, David R. TI Why study reproductive neuroscience? A clinical perspective SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 [Schmidt, Peter J.; Steinberg, Emma M.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2008 VL 69 IS 6 BP 972 EP 972 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 318LI UT WOS:000257092800014 PM 18683995 ER PT J AU Steinberg, EM Rubinow, DR Bartko, JJ Fortinsky, PM Haq, N Thompson, K Schmidt, PJ AF Steinberg, Emma M. Rubinow, David R. Bartko, John J. Fortinsky, Paige M. Haq, Nazli Thompson, Karla Schmidt, Peter J. TI A cross-sectional evaluation of perimenopausal depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MENOPAUSAL TRANSITION; PREMENSTRUAL-SYNDROME; POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; VASOMOTOR SYMPTOMS; SOMATIC SYMPTOMS; CONTROLLED-TRIAL; DOUBLE-BLIND; HOT FLASHES; DISORDERS AB Objective: Overall, the clinical spectrum of depression during the perimenopause is not well characterized. This cross-sectional study examined the following: (1) clinical characteristics of women who presented to the National Institute of Mental Health midlife mood disorders clinic (between March 1990 and January 2004) with perimenopausal major and minor depressions and (2) the impact on these characteristics of either a prior episode of depression or the presence of hot flushes. Method: Historical variables, reproductive status, symptom ratings, and plasma hormone measures were examined in 116 women between the ages of 40 and 55 years who met research criteria for perimenopause-related depression (a current episode of major or minor depression according to the Structured Clinical Interview for DSM-IV or Primary Care Evaluation of Mental Disorders supplemented with a past history form). Results: Clinical characteristics did not differ in those women with first-onset (39%) versus recurrent depressions or in those with (57%) and without hot flushes. Depressive episodes clustered in the later stages of the menopause transition and the first year postmenopause. Seven women (6%) reported a past postpartum major depression, and 55% of women reported a history of premenstrual dysphoria (PMD). Conclusions: We found no evidence that either hot flushes or a previous episode of depression conveys a distinct clinical profile in these women. The clustering of onsets of depression suggests the hormone events that characterize the late menopause transition may be relevant to the onset of this form of depression. Finally, although we observed a high rate of PMD, neither postpartum depression nor PMD are consistent accompaniments of perimenopausal depression. C1 [Steinberg, Emma M.; Fortinsky, Paige M.; Haq, Nazli; Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Thompson, Karla] NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10-CRC,Room 65340,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. EM peterschmidt@mail.nih.gov FU Intramural NIH HHS [Z01 MH002537-18] NR 41 TC 24 Z9 27 U1 6 U2 12 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 JUN PY 2008 VL 69 IS 6 BP 973 EP 980 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 318LI UT WOS:000257092800015 PM 18505304 ER PT J AU Garcia, AI Tabak, LA AF Garcia, A. Isabel Tabak, Lawrence A. TI Facing the future: the NIDCR celebrates its 60th anniversary SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material C1 [Garcia, A. Isabel; Tabak, Lawrence A.] NIDCR, Bethesda, MD 20892 USA. RP Garcia, AI (reprint author), NIDCR, Bldg 31,Room 2C39, Bethesda, MD 20892 USA. EM GarciaI@mail.nih.gov; TabakL@mail.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2008 VL 87 IS 6 BP 509 EP 509 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 304DN UT WOS:000256090300001 PM 18502956 ER PT J AU Sredni-Kenigsbuch, D Shohat, M Shohat, B Ben-Amitai, D Chan, CC David, M AF Sredni-Kenigsbuch, Dvora Shohat, Michael Shohat, Batia Ben-Amitai, Dan Chan, Chi-Chao David, Michael TI The novel tellurium immunomodulator AS101 inhibits interleukin-10 production and p38 MAPK expression in atopic dermatitis SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Letter ID CD4+T CELLS; IL-10; MICE AB The immunomodulator, AS101, inhibits production of IL-10, IL-4 and expression of p38 MAPK, while increasing production of IFN-gamma and IL-2. Together with its excellent clinical safety profile in humans, suggests a potential therapeutic use for AD. (c) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Sredni-Kenigsbuch, Dvora] Bar Ilan Univ, Interdisciplinary Dept, IL-52900 Ramat Gan, Israel. [Shohat, Michael; David, Michael] Schneider Childrens Hosp, Rabin Med Ctr, Dept Dermatol, Petah Tiqwa, Israel. [Shohat, Batia] Schneider Childrens Hosp, Rabin Med Ctr, Cellular Immunol Unit, Petah Tiqwa, Israel. [Ben-Amitai, Dan] Schneider Childrens Hosp, Rabin Med Ctr, Pediat Dermatol Unit, Petah Tiqwa, Israel. [Chan, Chi-Chao] NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Sredni-Kenigsbuch, D (reprint author), Bar Ilan Univ, Interdisciplinary Dept, IL-52900 Ramat Gan, Israel. EM srednid@mait.biu.ac.il NR 10 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JUN PY 2008 VL 50 IS 3 BP 232 EP 235 DI 10.1016/j.jdermsci.2007.12.007 PG 4 WC Dermatology SC Dermatology GA 303VY UT WOS:000256070200008 PM 18242062 ER PT J AU Bada, HS Langer, J Twomey, J Bursi, C Lagasse, L Bauer, CR Shankaran, S Lester, BM Higgins, R Maza, PL AF Bada, Henrietta S. Langer, John Twomey, Jean Bursi, Charlotte Lagasse, Linda Bauer, Charles R. Shankaran, Seetha Lester, Barry M. Higgins, Rosemary Maza, Penelope L. TI Importance of stability of early living arrangements on behavior outcomes of children with and without prenatal drug exposure SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE prenatal cocaine; prenatal opiate; out-of-home-care; child behavior ID MATERNAL LIFE-STYLE; SUBSTANCE-ABUSING MOTHERS; FAMILY FOSTER-CARE; MENTAL-HEALTH; COCAINE EXPOSURE; KINSHIP CARE; PLACEMENT; PREGNANCY; ATTACHMENT; INFANTS AB Objective: We evaluated whether living arrangements of children with or without prenatal drug exposure would be associated with their behavior outcomes and adaptive functioning. Methods: A total of 1388 children with or without prenatal cocaine or opiate exposure were enrolled in a longitudinal cohort study at I month of age, were seen at intervals, tracked over time for their living situation, and evaluated for behavior problems and adaptive functioning at 3 years of age. The Child Behavior Checklist and Vineland Adaptive Behavior Scales were administered. Using multiple regression models, we determined the factors that would predict behavior problems and adaptive functioning. Results: Of the children enrolled, 1092 children were evaluated. Total and externalizing behavior problems T scores of children in relative care were lower (better) than those in parental care; externalizing behavior scores were lower than those in nonrelative care (p < .05). Total behavior problem scores increased 2.3 and 1.3 points, respectively, with each move per year and each year of Child Protective Services involvement. Compared to children in nonrelative care, those in parental or relative care had higher (better) scores in the Vineland Adaptive Behavior Scales total composite (p < .023), communication (p < .045), and daily living (p < .001). Each caretaker change was associated with a decrease of 2.65 and 2.19 points, respectively, in communication and daily living scores. Conclusion: Children's living arrangements were significantly associated with childhood behavior problems and adaptive functioning. The instability of living situation was also a significant predictor of these outcomes. While family preservation continues to be the goal of the child welfare system, expediting decision toward permanency remains paramount once children are placed in faster care. C1 [Bada, Henrietta S.] Univ Kentucky, Coll Med, Dept Pediat, Lexington, KY 40536 USA. [Langer, John; Maza, Penelope L.] RTI Int, Res Triangle Pk, NC USA. [Twomey, Jean] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Lagasse, Linda; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Dept Pediat, Providence, RI 02912 USA. [Bursi, Charlotte] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Bauer, Charles R.] Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Higgins, Rosemary] NICHHD, Bethesda, MD 20892 USA. [Maza, Penelope L.] Adm Children Youth & Families, Washington, DC USA. RP Bada, HS (reprint author), Univ Kentucky, Coll Med, Dept Pediat, 800 Rose St,Room MS 477, Lexington, KY 40536 USA. EM hbada2@uky.edu FU NICHD NIH HHS [U10 HD027904, U10 HD021415, U10 HD021385, U01 HD 36790, N01-HD-2-3159, N1HD23159A, U10 HD021397, U01 HD 27904, U10 HD 21385, U10 HD 21397, U10 HD042638, U10 HD 21415, U01 HD036790] NR 43 TC 23 Z9 23 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 2008 VL 29 IS 3 BP 173 EP 182 DI 10.1097/DBP.0b013e3181644a79 PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 314JE UT WOS:000256804900005 PM 18349707 ER PT J AU Speliotes, EK Massaro, JM Hoffmann, U Foster, MC Sahani, DV Hirschhorn, JN O'Donnell, CJ Fox, CS AF Speliotes, Elizabeth K. Massaro, Joseph M. Hoffmann, Udo Foster, Meredith C. Sahani, Dushyant V. Hirschhorn, Joel N. O'Donnell, Christopher J. Fox, Caroline S. TI Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE computed tomography scan; fatty liver; measurement; metabolic syndrome; reproducibility AB Background and Aims: Fatty liver is the hepatic manifestation of obesity, but community-based assessment of fatty liver among unselected patients is limited. We sought to determine the feasibility of and optimal protocol for quantifying fat content in the liver in the Framingham Heart Study using multidetector computed tomography (MDCT) scanning. Methods: Participants (n = 100, 49% women, mean age 59.4 years, mean body mass index 27.8 kg/m(2)) were drawn from the Framingham Heart Study cohort. Two readers measured the attenuation of the liver, spleen, paraspinal muscles, and an external standard from MDCT scans using multiple slices in chest and abdominal scans. Results: The mean measurement variation was larger within a single axial computed tomography (CT) slice than between multiple axial CT slices for the liver and spleen, whereas it was similar for the paraspinal muscles. Measurement variation in the liver, spleen, and paraspinal muscles was smaller in the abdomen than in the chest. Three versus six measures of attenuation in the liver and two versus three measures in the spleen gave reproducible measurements of tissue attenuation (intraclass correlation coefficient [ICCC] of 1 in the abdomen). Intrareader and interreader reproducibility (ICCC) of the liver-to-spleen ratio was 0.98 and 0.99, the liver-to-phantom ratio was 0.99 and 0.99, and the liver-to-muscle ratio was 0.93 and 0.86, respectively. Conclusion: One cross-sectional slice is adequate to capture the majority of variance of fat content in the liver per individual. Abdominal scan measures as compared to chest scan measures of fat content in the liver are more precise. The measurement of fat content in the liver on MDCT scans is feasible and reproducible. C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Dept Stat, Boston, MA 02215 USA. [Hirschhorn, Joel N.] Childrens Hosp, Dept Endocrinol & Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] Broad Inst Harvard, Dept Med & Populat Genet, Cambridge, MA USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] MIT, Cambridge, MA 02139 USA. [Foster, Meredith C.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 15 Fruit St, Boston, MA 02114 USA. EM espeliotes@partners.org; foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU NHLBI NIH HHS [N01 HC025195, N01-HC25195, N01HC25195]; NIDDK NIH HHS [F32 DK079466-01, F32 DK079466, K23 DK080145, K23 DK080145-01, K23DK080145-01, T32 DK007191, T32 DK007191-32, T32 DK07191-32] NR 8 TC 53 Z9 54 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JUN PY 2008 VL 23 IS 6 BP 894 EP 899 DI 10.1111/j.1440-1746.2008.05420.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 310OY UT WOS:000256540200014 PM 18565021 ER PT J AU Arora, NK AF Arora, Neeraj K. TI Clarification of issues raised in the editorial "A New Age for Cancer Information Seeking: Are We Better Off Now?" SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Arora, NK (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4005,MSC 7344, Bethesda, MD 20892 USA. EM aroran@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2008 VL 23 IS 6 BP 893 EP 893 DI 10.1007/s11606-008-0531-2 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500032 PM 18274829 ER PT J AU Ravichandran, V Major, EO AF Ravichandran, Veerasamy Major, Eugene O. TI DNA-binding transcription factor NF-1A negatively regulates JC virus multiplication SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NUCLEAR FACTOR-I; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CEREBROSPINAL-FLUID; CONTROL REGION; POLYOMAVIRUS; PROTEIN; GENE; EXPRESSION; SEQUENCES; INHIBITION AB JC virus (JCV) DNA replication occurs in the nuclei of infected cells. The level of JCV genome expression depends on nucleotide sequences in the viral regulatory region and their interaction with host-cell nuclear transcription factors. Our previous studies showed a higher level of NF-1X in JCV-permissive cells compared with the other members of the NF-1 family, NF-1A, B and C, which suggests that NF-1X plays a positive role in JCV multiplication. It remained unclear whether a reduction in the level of NF-1A, which is expressed abundantly in JCV-non-permissive cell types, leads to an increase in JCV multiplication. In this study, we show that downregulation of NF-1A expression in JCV-non-susceptible progenitor and HeLa cells results in a reversion to susceptibility for JCV multiplication. These data demonstrate that a higher level of NF-1A protein in JCV-non-permissive cell types, compared with the level of NF-1X, may be acting as a negative regulator at the JCV promoter to control JCV multiplication. C1 [Ravichandran, Veerasamy; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, Natl Inst Hlth, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov FU Intramural NIH HHS [Z01 NS001983-36] NR 29 TC 15 Z9 15 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 2008 VL 89 BP 1396 EP 1401 DI 10.1099/vir.0.2008/000059-0 PN 6 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 312QZ UT WOS:000256687200009 PM 18474555 ER PT J AU Ji, W Foo, JN O'Roak, B Zhao, H Larson, M Simon, D Newton-Cheh, C State, M Levy, D Lifton, R AF Ji, W. Foo, J. N. O'Roak, B. Zhao, H. Larson, M. Simon, D. Newton-Cheh, C. State, M. Levy, D. Lifton, R. TI Rare independent mutations in renal salt handling genes contribute to blood pressure variation SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Ji, W.; Foo, J. N.; O'Roak, B.; Zhao, H.; Simon, D.; State, M.; Lifton, R.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Larson, M.; Newton-Cheh, C.; Levy, D.] NHLBI, Framingham Heart Study, Framingham, MA USA. RI Foo, Jia Nee/D-6069-2014 OI Foo, Jia Nee/0000-0001-9899-2308 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S7 EP S7 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197000031 ER PT J AU Sharabi, Y Goldstein, D Pechnik, S Holmes, C Pacak, K Eisenhofer, G AF Sharabi, Y. Goldstein, D. Pechnik, S. Holmes, C. Pacak, K. Eisenhofer, G. TI Pseudopheochromocytoma - a new form of secondary hypertension in patients with paroxysmal and labile blood pressure SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Sharabi, Y.; Goldstein, D.; Pechnik, S.; Holmes, C.; Pacak, K.; Eisenhofer, G.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S143 EP S143 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197001020 ER PT J AU Sharabi, Y Goldstein, D Moak, J AF Sharabi, Y. Goldstein, D. Moak, J. TI Low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Sharabi, Y.; Goldstein, D.; Moak, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S57 EP S57 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197000243 ER PT J AU Timmers, H Brouwers, F Hermus, A Sweep, F Verhofstad, A Verbeek, A Pacak, K Lenders, J AF Timmers, H. Brouwers, F. Hermus, A. Sweep, F. Verhofstad, A. Verbeek, A. Pacak, K. Lenders, J. TI Long-term outcome of patients after surgical resection of apparently benign pheochromocytoma SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Timmers, H.; Brouwers, F.; Hermus, A.; Sweep, F.; Verhofstad, A.; Verbeek, A.; Lenders, J.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Pacak, K.] NICHHD, NIH, Bethesda, MD 20892 USA. RI Hermus, A.R.M.M./H-8043-2014; Verbeek, A.L.M./H-8103-2014; Sweep, C.G.J./H-8096-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S71 EP S71 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197000308 ER PT J AU Terabe, M Tagaya, Y Zhu, Q Granger, L Roederer, M Waldmann, TA Berzofsky, JA AF Terabe, Masaki Tagaya, Yutaka Zhu, Qing Granger, Larry Roederer, Mario Waldmann, Thomas A. Berzofsky, Jay A. TI IL-15 expands unconventional CD8 alpha alpha NK1.1(+) T cells but not V alpha 14J alpha 18(+) NKT cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; VIRUS-SPECIFIC CD8(+); NATURAL-KILLER; IN-VIVO; TRANSGENIC MICE; MEMORY; HOMEOSTASIS; EXPRESSION; THYMUS; DIFFERENTIATION AB Despite recent gains in knowledge regarding CD1d-restricted NKT cells, very little is understood of non-CD1d-restricted NKT cells such as CD8(+)NK1.1(+) T cells, in part because of the very small proportion of these cells in the periphery. In this study we took advantage of the high number of CD8(+)NK1.1(+) T cells in IL-15-transgenic mice to characterize this T cell population. In the IL-15-transgenic mice, the absolute number of CD1d-tetramer(+) NKT cells did not increase, although IL-15 has been shown to play a critical role in the development and expansion of these cells. The CD8(+)NK1.1(+) T cells in the IL-15-transgenic mice did not react with CD1d-tetramer. Approximately 50% of CD8(+)NK1.1(+) T cells were CD8 alpha alpha. In contrast to CD4(+)NK1.1(+) T cells, which were mostly CD1d-restricted NKT cells and of which similar to 70% were CD69(+)CD44(+), similar to 70% of CD8(+)NK1.1(+) T cells were CD69(-)CD44(+). We could also expand similar CD8 alpha alpha NK1.1(+) T cells but not CD4(+) NKT cells from CD8 alpha(+)beta(-) bone marrow cells cultured ex vivo with IL-15. These results indicate that the increased CD8 alpha alpha NK1.1(+) T cells are not activated conventional CD8(+) T cells and do not arise from conventional CD8 alpha beta precursors. CD8 alpha alpha NK1.1(+) T cells produced very large amounts of IFN-gamma and degranulated upon TCR activation. These results suggest that high levels of IL-15 induce expansion or differentiation of a novel NK1.1(+) T cell subset, CD8 alpha alpha NK1.1(+) T cells, and that IL-15-transgenic mice may be a useful resource for studying the functional relevance of CD8(+)NK1.1(+) T cells. C1 [Terabe, Masaki; Zhu, Qing; Berzofsky, Jay A.] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. [Tagaya, Yutaka; Waldmann, Thomas A.] NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. [Granger, Larry] NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. [Roederer, Mario] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Terabe, M (reprint author), NCI, NIH, Vaccine Branch, Bldg 10,Room 613-12,9000 Rockville Pike, Bethesda, MD 20892 USA. EM terabe@mail.nih.gov; ytagaya@helix.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS [Z99 AI999999, Z01 AI005019-07] NR 44 TC 16 Z9 16 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 JUN 1 PY 2008 VL 180 IS 11 BP 7276 EP 7286 PG 11 WC Immunology SC Immunology GA 324GX UT WOS:000257507300024 PM 18490727 ER PT J AU Cox, CA Shi, GP Yin, HE Vistica, BP Wawrousek, EF Chan, CC Gery, I AF Cox, Catherine A. Shi, Guangpu Yin, Hongen Vistica, Barbara P. Wawrousek, Eric F. Chan, Chi-Chao Gery, Igal TI Both Th1 and Th17 are immunopathogenic but differ in other key biological activities SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NEO-SELF ANTIGEN; T-CELLS; OCULAR INFLAMMATION; NONSPECIFIC CELLS; EPITHELIAL-CELLS; TGF-BETA; IL-17; LYMPHOCYTES; INDUCTION AB The role of Th17 lymphocytes in immunopathogenic processes has been well established, but little is known about their basic cell features. In this study, we compared polarized Th1 and Th17 for key biological activities related to pathogenicity and trafficking. Th1 and Th17 lineages were derived from TCR-transgenic CD4 murine cells specific against hen egg lysozyme. When adoptively transferred into mice expressing hen egg lysozyme in their eyes, both Th1 and Th17 induced ocular inflammation but with slight differences in histological pathology. PCR analysis revealed selective expression of IFN-gamma or IL-17 in eyes of Th1 or Th17 recipients, respectively. Additionally, Th1 and Th17 were found to differ in three other key activities: 1) Th17 cells were inferior to Th1 cells in their capacity to trigger massive lymphoid expansion and splenomegaly; 2) the proportion of Th1 cells among infiltrating cells in inflamed recipient eyes declined rapidly, becoming a minority by day 7, whereas Th17 cells remained in the majority throughout this period; and 3) remarkable differences were noted between Th1 and Th17 cells in their expression of certain surface markers. In particular, reactivated Th1 expressed higher levels of CD49d and alpha(4)beta(7) (mucosal homing) in vitro and higher levels of CXCR3 (Th1 trafficking) in vivo. Reactivated Th17, however, expressed higher levels of a,13, (epithelial tissue homing) and CD38 (activation, maturation and trafficking) in vitro, but in vivo Th17 expressed higher levels of alpha(4)beta(7) and CCR6 (lymphocyte trafficking). These data reveal that Th1 and Th17 cells differ in several key biological activities influencing migration and pathogenic behavior during inflammatory disease. C1 [Cox, Catherine A.; Shi, Guangpu; Yin, Hongen; Vistica, Barbara P.; Chan, Chi-Chao; Gery, Igal] Natl Inst Hlth, NEI, Immunol Lab, Bethesda, MD 20892 USA. [Wawrousek, Eric F.] Natl Inst Hlth, NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. [Cox, Catherine A.] Howard Hughes Med Inst, Natl Inst Hlth, Res Scholars Program, Bethesda, MD 20814 USA. RP Gery, I (reprint author), Natl Inst Hlth, NEI, Immunol Lab, Bldg 10,Room 10N208, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 54 TC 49 Z9 50 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2008 VL 180 IS 11 BP 7414 EP 7422 PG 9 WC Immunology SC Immunology GA 324GX UT WOS:000257507300038 PM 18490741 ER PT J AU Woszczek, G Chen, LY Nagineni, S Shelhamer, JH AF Woszczek, Grzegorz Chen, Li-Yuan Nagineni, Sahrudaya Shelhamer, James H. TI IL-10 inhibits cysteinyl leukotriene-induced activation of human monocytes and monocyte-derived dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; KAPPA-B ACTIVATION; AIRWAY INFLAMMATION; MURINE MODEL; T-CELLS; RECEPTOR; INTERLEUKIN-10; ASTHMA; EXPRESSION; ALLERGEN AB The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells. Herein we show that cysLT-induced activation and chemotaxis of human monocytes and monocyte-derived immature dendritic cells (iDC) are inhibited by IL-10 pretreatment. IL-10 down-regulated cysLT type 1 and 2 receptors' mRNA in a time- and concentration-dependent fashion. cysLT induced activation of monocytes and iDCs measured by intracellular calcium flux and immediate-early gene expression (FBJ murine osteosarcoma viral oncogen homolog B and early growth response-2) was potently decreased by IL-10 and by the cysLT antagonist NIK571. Chemotaxis of monocytes and iDCs to increasing concentrations of leukotriene D-4 (LTD4) was also inhibited by IL-10. LTD4 enhanced iDC migration in response to CCL5. IL-10 selectively inhibited LTD4-induced chemotaxis without affecting migration to CCL5. These data indicate that cysLT-induced activation of human monocytes and dendritic cells may be specifically inhibited by IL-10, suggesting a direct link between the 5-lipoxygenase proinflammatory pathway and IL-10 regulatory mechanisms. Antileukotriene therapies may reproduce some regulatory mechanisms played by IL-10 in inflammatory processes. C1 [Woszczek, Grzegorz; Chen, Li-Yuan; Nagineni, Sahrudaya; Shelhamer, James H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 2C145,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jshelhamer@cc.nih.gov RI Woszczek, Grzegorz/H-5792-2012 FU Intramural NIH HHS [Z01 CL008071-04] NR 36 TC 21 Z9 25 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2008 VL 180 IS 11 BP 7597 EP 7603 PG 7 WC Immunology SC Immunology GA 324GX UT WOS:000257507300059 PM 18490762 ER PT J AU Sato, T Shimosato, T Alvord, WG Klinman, DM AF Sato, Takashi Shimosato, Takeshi Alvord, W. Gregory Klinman, Dennis M. TI Suppressive oligodeoxynucleotides inhibit silica-induced pulmonary inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED IMMUNE ACTIVATION; NADPH OXIDASE; INDUCED APOPTOSIS; ALVEOLAR MACROPHAGES; OXIDATIVE STRESS; MURINE MODEL; INDUCED ARTHRITIS; INTERFERON-GAMMA; LUNG FIBROSIS; MICE AB Inhalation of silica-containing dust particles induces silicosis, an inflammatory disease of the lungs characterized by the infiltration of macrophages and neutrophils into the lungs and the production of proinflammatory cytokines, chemokines, and reactive oxygen species (ROS). Synthetic oligodeoxynucleotides (ODN) expressing "immunosuppressive motifs" were recently shown to block pathologic inflammatory reactions in murine models of autoinumme disease. Based on those findings, the potential of suppressive ODN to prevent acute murine silicosis was examined. In vitro studies indicate that suppressive ODN blunt silica-induced macrophage toxicity. This effect was associated with a reduction in ROS production and p47phox expression (a subunit of NADPH oxidase key to ROS generation). In vivo studies show that pretreatment with suppressive (but not control) ODN reduces silicadependent pulmonary inflammation, as manifest by fewer infiltrating cells, less cytokine/chemokine production, and lower levels of ROS (p < 0.01 for all parameters). Treatment with suppressive ODN also reduced disease severity and improved the survival (p < 0.05) of mice exposed to silica. C1 [Sato, Takashi; Shimosato, Takeshi; Klinman, Dennis M.] NCI, Expt Immunol Lab, Frederick, MD 21702 USA. [Alvord, W. Gregory] NCI, Data Management Serv Inc, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Expt Immunol Lab, Bldg 567,Room 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 52 TC 30 Z9 34 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 JUN 1 PY 2008 VL 180 IS 11 BP 7648 EP 7654 PG 7 WC Immunology SC Immunology GA 324GX UT WOS:000257507300064 PM 18490767 ER PT J AU Fauci, AS AF Fauci, Anthony S. CA NIAID TB Working Grp TI Multidrug-resistant and extensively drug-resistant tuberculosis: The National Institute of Allergy and Infectious Diseases research agenda and recommendations for priority research SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article C1 [Fauci, Anthony S.; NIAID TB Working Grp] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Via, Laura/0000-0001-6074-9521; Polis, Michael/0000-0002-9151-2268 NR 24 TC 75 Z9 76 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2008 VL 197 IS 11 BP 1493 EP 1498 DI 10.1086/587904 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 299IE UT WOS:000255748500003 PM 18426366 ER PT J AU Diep, BA Stone, GG Basuino, L Graber, CJ Miller, A des Etages, SA Jones, A Palazzolo-Ballance, AM Perdreau-Remington, F Sensabaugh, GF DeLeo, FR Chambers, HF AF Diep, Binh An Stone, Gregory G. Basuino, Li Graber, Christopher J. Miller, Alita des Etages, Shelley-Ann Jones, Alison Palazzolo-Ballance, Amy M. Perdreau-Remington, Francoise Sensabaugh, George F. DeLeo, Frank R. Chambers, Henry F. TI The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: Convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the Network-on-Antimicrobial-Resistance-in-Staphylococcus-aureus CY MAR 05, 2007 CL Reston, VA SP Network Antimicrobial Resistance Staphylococcus aureus ID PANTON-VALENTINE LEUKOCIDIN; SOFT-TISSUE INFECTIONS; COMMUNITY-ASSOCIATED MRSA; POPULATION-DYNAMICS; ANTIBIOTIC-RESISTANCE; WHOLE GENOME; FITNESS COST; EMERGENCE; GENES; PNEUMONIA AB The epidemic character of community-associated methicillin-resistant Staphylococcus aureus, especially the geographically widespread clone USA300, is poorly understood. USA300 isolates carry a type IV staphylococcal chromosomal cassette mec (SCCmec) element conferring beta-lactam antibiotic class resistance and a putative pathogenicity island, arginine catabolic mobile element (ACME). Physical linkage between SCCmec and ACME suggests that selection for antibiotic resistance and for pathogenicity may be interconnected. We constructed isogenic mutants containing deletions of SCCmec and ACME in a USA300 clinical isolate to determine the role played by these elements in a rabbit model of bacteremia. We found that deletion of type IV SCCmec did not affect competitive fitness, whereas deletion of ACME significantly attenuated the pathogenicity or fitness of USA300. These data are consistent with a model in which ACME enhances growth and survival of USA300, allowing for genetic "hitch-hiking" of SCCmec. SCCmec in turn protects against exposure to beta-lactams. C1 [Diep, Binh An; Basuino, Li; Graber, Christopher J.; Perdreau-Remington, Francoise; Chambers, Henry F.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Infect Dis, Dept Med, San Francisco, CA 94110 USA. [Diep, Binh An; Sensabaugh, George F.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Stone, Gregory G.; Miller, Alita; des Etages, Shelley-Ann; Jones, Alison] Pfizer Inc, Groton Labs, Groton, CT 06340 USA. [Palazzolo-Ballance, Amy M.; DeLeo, Frank R.] NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Chambers, HF (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Infect Dis, Dept Med, Bldg 30,Rm 3400,1001 Potrero Ave, San Francisco, CA 94110 USA. EM hchambers@medsfgh.ucsf.edu OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS; NIAID NIH HHS [5T32AI060537-02, R01 AI070289]; ODCDC CDC HHS [R01 CCR923381] NR 40 TC 230 Z9 235 U1 1 U2 18 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 JUN 1 PY 2008 VL 197 IS 11 BP 1523 EP U35 DI 10.1086/587907 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 299IE UT WOS:000255748500008 PM 18700257 ER PT J AU Martin, JE Pierson, TC Graham, BS AF Martin, Julie E. Pierson, Theodore C. Graham, Barney S. TI The first antibody responses to DNA vaccines in humans - Reply to Rottinghaus and Poland SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; CANDIDATE VACCINE; CLINICAL-TRIAL; INFECTION; NEUTRALIZATION; SURFACE C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Pierson, Theodore C.] NIAID, Viral Dis Lab, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Rm 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 12 TC 2 Z9 2 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 JUN 1 PY 2008 VL 197 IS 11 BP 1628 EP 1629 DI 10.1086/587945 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 299IE UT WOS:000255748500022 ER PT J AU de Falco, S Esposito, G Venuti, P Bornstein, MH AF de Falco, S. Esposito, G. Venuti, P. Bornstein, M. H. TI Fathers' play with their Down Syndrome children SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE Down Syndrome; fathering; parenting; child play ID EMOTIONAL AVAILABILITY; SYMBOLIC PLAY; YOUNG-CHILDREN; DEVELOPMENTAL-DISABILITIES; INFANT ATTACHMENT; MOTHER-TODDLER; PRETEND PLAY; PARENTS; STRESS; PATTERNS AB Background In children with Down Syndrome (DS), as in other groups of special needs children, development depends crucially on the degree to which parents provide appropriate stimulation and effective support. The majority of recent studies investigating interactions between parents and children with DS have been conducted on mothers. Method Through observation of child solitary play, child collaborative play with their father, and father play with their child, the current study focused on paternal contributions to child play in association with the effective quality of father-child interactions. A total of 19 children (M chronological age = 35.32 months, SD = 10.35; M mental age = 19.58, SD = 5.43) with DS and their fathers participated in the study. Two 10-min sessions, of child solitary play and collaborative play with their father, were videorecorded. A coding system for exploratory and symbolic play was applied to both sessions, and the Emotional Availability (EA) Scales were independently applied to the collaborative play session as a measure of the effective quality of the father-child interaction. Results Children showed more symbolic play during collaborative sessions compared with solitary sessions. Bivariate correlations showed positive associations between father play and child exploratory and symbolic play. Cluster analysis identified dyads in low, medium and high EA groups, which differed in terms of each partner's play. Specifically, both fathers and children of high EA dyads were more likely to show more symbolic play and less exploratory play than those with low EA dyads. Conclusions Our findings enrich the theoretical perspective that dyadic interactions based on emotional involvement may lead to enhanced cognitive functioning in children with DS. C1 [de Falco, S.; Esposito, G.; Venuti, P.] Univ Trent, Dept Cognit Sci & Educ, I-38068 Rovereto, TN, Italy. [Bornstein, M. H.] NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP de Falco, S (reprint author), Univ Trent, Dept Cognit Sci & Educ, Via Matteo Del Ben 5, I-38068 Rovereto, TN, Italy. EM defalco@form.unitn.it RI Esposito, Gianluca/B-1374-2012 OI Esposito, Gianluca/0000-0002-9442-0254 FU Intramural NIH HHS NR 77 TC 19 Z9 20 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD JUN PY 2008 VL 52 BP 490 EP 502 DI 10.1111/j.1365-2788.2008.01052.x PN 6 PG 13 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 301VV UT WOS:000255925000003 PM 18373561 ER PT J AU Cooper, KD Sontheimer, RD Dutz, J Hwang, ST Nickoloff, BJ Shimada, S Kulesz-Martin, M Bickenbach, JR AF Cooper, Kevin D. Sontheimer, Richard D. Dutz, Jan Hwang, Sam T. Nickoloff, Brian J. Shimada, Shinji Kulesz-Martin, Molly Bickenbach, Jackie R. TI 56th annual Montagna Symposium on the biology of skin: Epidermal T-Cell interactions - Clinicopathological and basic mechanisms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material C1 [Bickenbach, Jackie R.] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Cooper, Kevin D.] Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA. [Sontheimer, Richard D.] Univ Oklahoma, Hlth Sci Ctr, Dept Dermatol, Oklahoma City, OK USA. [Dutz, Jan] Univ British Bethesda, Dept Dermatol & Skin Sci, Vancouver, BC, Canada. [Dutz, Jan] Univ British Bethesda, Child & Family Res Inst, Vancouver, BC, Canada. [Hwang, Sam T.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nickoloff, Brian J.] Loyola Univ, Med Ctr, Dept Pathol, Chicago, IL 60611 USA. [Shimada, Shinji] Univ Yamanashi, Fac Med, Dept Dermatol, Yamanashi, Japan. [Kulesz-Martin, Molly] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. RP Bickenbach, JR (reprint author), Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, 1-457 BSB 51 Newton Rd, Iowa City, IA 52242 USA. EM jackie-bickenbach@uiowa.edu OI Cooper, Kevin/0000-0002-1986-3602 FU NIAMS NIH HHS [P50 AR055508, 5 R13 AR009431-42, P30 AR039750, R13 AR009431] NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2008 VL 128 IS 6 BP 1351 EP 1353 DI 10.1038/jid.2008.99 PG 3 WC Dermatology SC Dermatology GA 302FG UT WOS:000255953600003 PM 18478009 ER PT J AU Pastore, S Mascia, F Mariani, V Girolomoni, G AF Pastore, Saveria Mascia, Francesca Mariani, Valentina Girolomoni, Giampiero TI The epidermal growth factor receptor system in skin repair and inflammation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review ID HEPARIN-BINDING EGF; CULTURED HUMAN KERATINOCYTES; TYROSINE-PHOSPHATASE-KAPPA; PROTEIN-KINASE INHIBITORS; TOLL-LIKE-RECEPTORS; FACTOR-ALPHA; PSORIATIC EPIDERMIS; AUTOCRINE GROWTH; ANTIMICROBIAL PEPTIDES; CHEMOKINE EXPRESSION AB The epidermal growth factor (EGF) family comprises multiple mediators such as transforming growth factor-alpha, amphiregulin, heparin binding-EGF, and epiregulin, which are crucially involved in the tissue-specific proliferation/differentiation homeostasis. Typically, they act in an autocrine and paracrine manner on their specific cell membrane receptor and mount an effective reparative response to any attack to biophysical integrity. In addition, the EGFR can be activated by transactivation from a variety of G-protein-coupled receptors, integrins, and cytokine receptors, so that it acts as the major transducer of disparate cell functions, including changes in proliferation rate, cellular shape, attachment and motility, and regulation of proinflammatory activation. However, numerous experimental observations indicate that the different EGFR ligands are not redundant, but may rather provide distinct and specific contributions to keratinocyte functions. Importantly, increasing evidence now suggests that the EGFR pathway has a major impact on the inflammatory/immune reactions of the skin, in the apparent effort of enhancing innate immune defense while opposing overactivation of keratinocyte pro-inflammatory functions. This review covers the molecular mechanisms and functions activated by this major growth factor system in the regulation of keratinocyte biology and focuses on the complex contribution of EGFR signaling to the inflammatory processes in the skin. C1 [Girolomoni, Giampiero] Univ Verona, Dept Biomed & Surg Sci, Sect Dermatol & Venerol, I-37126 Verona, Italy. [Pastore, Saveria; Mariani, Valentina] IRCCS, Ist Dermapat Immacolata, Lab Tissue Engn & Cutaneous Physiopathol, Rome, Italy. [Mascia, Francesca] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Girolomoni, G (reprint author), Univ Verona, Dept Biomed & Surg Sci, Sect Dermatol & Venerol, Piazzale A Stefani 1, I-37126 Verona, Italy. EM giampiero.girolomoni@univr.it NR 106 TC 195 Z9 200 U1 2 U2 23 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 JUN PY 2008 VL 128 IS 6 BP 1365 EP 1374 DI 10.1038/sj.jid.5701184 PG 10 WC Dermatology SC Dermatology GA 302FG UT WOS:000255953600009 PM 18049451 ER PT J AU Farasat, S Wei, MH Ahvazi, B Liewehr, DJ Steinberg, SM Bale, SJ Fleckman, P Toro, JR AF Farasat, S. Wei, M. H. Ahvazi, B. Liewehr, D. J. Steinberg, S. M. Bale, S. J. Fleckman, P. Toro, J. R. TI Clinical, genetic, and quality of life studies of autosomal recessive congenital ichthyosis in 104 patients SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the AFMR Eastern Region 2008 CY APR 09, 2008 CL Washinton, DC SP AFMR Eastern Reg C1 [Farasat, S.; Wei, M. H.; Ahvazi, B.; Liewehr, D. J.; Steinberg, S. M.; Toro, J. R.] NIH, Bethesda, MD 20892 USA. [Bale, S. J.] GeneDx Inc, Gaithersburg, MD USA. [Fleckman, P.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 2008 VL 56 IS 5 BP 806 EP 807 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 311FP UT WOS:000256586400027 ER PT J AU Korman, BD Le, J Kastner, D Remmers, E Alba, M Alevizos, I Nikolov, N Illei, G Smith, J AF Korman, B. D. Le, J. Kastner, D. Remmers, E. Alba, M. Alevizos, I. Nikolov, N. Illei, G. Smith, J. TI Association of a common variant of the signal transducer and activator of transcription 4 (STAT4) gene with primary Sjogren's syndrome SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Eastern Region of the American-Federation-for-Medical-Research CY APR09, 2008 CL Washington, DC SP Amer Federat Med Res, Eastern Reg C1 [Korman, B. D.; Le, J.; Kastner, D.; Remmers, E.] NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. [Alba, M.; Alevizos, I.; Nikolov, N.; Illei, G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA. [Alba, M.; Alevizos, I.; Nikolov, N.; Illei, G.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, Bethesda, MD USA. [Smith, J.] NEI, Off Clin Director, Bethesda, MD 20892 USA. [Korman, B. D.] NIH, Clin Res Training Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 2008 VL 56 IS 5 BP 808 EP 808 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 311FP UT WOS:000256586400032 ER PT J AU Obafemi, AA Marini, JC Obafemi, AA AF Obafemi, A. A. Marini, J. C. Obafemi, A. A. TI Popcorn calcification in osteogenesis imperfecta SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the AFMR Eastern Region 2008 CY APR 09, 2008 CL Washinton, DC SP AFMR Eastern Reg C1 [Obafemi, A. A.; Marini, J. C.] NICHD, NIH, Bone & Extracellular Matrix Branch, Bethesda, MD USA. [Obafemi, A. A.] UMDNJ New Jersey Med Sch, Newark, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 2008 VL 56 IS 5 BP 809 EP 810 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 311FP UT WOS:000256586400035 ER PT J AU Korman, BD Kastner, D Remmers, E Lee, H Bae, S Gregersen, P Criswell, L AF Korman, B. D. Kastner, D. Remmers, E. Lee, H. Bae, S. Gregersen, P. Criswell, L. TI Single nucleotide polymporhisms in TNFAIP3, TRAF1/C5, and PTPN22 regions show association with Caucasian systemic lupus erythematosus but not with korean rheumatoid arthritis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the AFMR Eastern Region 2008 CY APR 09, 2008 CL Washinton, DC SP AFMR Eastern Reg C1 [Korman, B. D.; Kastner, D.; Remmers, E.] NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. [Lee, H.; Bae, S.] Hanyang Univ, Coll Med, Dept Rheumatol, Seoul 133791, South Korea. [Lee, H.; Bae, S.] Hosp Rheumat Dis, Seoul, South Korea. [Lee, H.; Gregersen, P.] Robert S Boas Ctr Genet & Genom, Feinstein Inst Biomed Res, Manhasset, NY USA. [Criswell, L.] Univ Calif San Francisco, Dept Rheumatol, San Francisco, CA 94143 USA. [Korman, B. D.] NIH, Clin Res Training Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 2008 VL 56 IS 5 BP 812 EP 812 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 311FP UT WOS:000256586400041 ER PT J AU Wolf, SM Paradise, J Caga-anan, C AF Wolf, Susan M. Paradise, Jordan Caga-anan, Charlisse TI The law of incidental findings in human subjects research: Establishing researchers' duties SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article; Proceedings Paper CT Symposium on Findings in Human Subjects Research - From Imaging to Genomics CY MAY, 2007 CL Univ Minnesota, Minneapolis, MN HO Univ Minnesota ID CLINICAL-RESEARCH; CT COLONOGRAPHY; EXTRACOLONIC FINDINGS; GENETIC INFORMATION; MR-IMAGES; BRAIN; POPULATION; PARTICIPANTS; LITIGATION; DISCLOSURE AB Research technologies can now produce so much information that there is significant potential for incidental findings (IFs). These are findings generated in research that are beyond the aims of the study. Current law and federal regulations offer no direct guidance on how to deal with IFs in research, nor is there adequate professional or institutional guidance. We advocate a defined set of researcher duties based on law and ethics and recommend a pathway to be followed in handling IFs in research. This article traces the underlying ethical and legal theories supporting researcher duties to manage IFs, including duties to develop a plan for management in the research protocol, to discuss the possibility of and management plan for IFs in the informed consent process, and to address, evaluate, and ultimately offer to disclose IFs of potential clinical or reproductive significance to research participants when they arise. C1 [Wolf, Susan M.; Paradise, Jordan; Caga-anan, Charlisse] Univ Minnesota, Consortium Law & Values Hlth Environm & Life Sci, Minneapolis, MN 55455 USA. [Wolf, Susan M.] NIH, Bethesda, MD 20892 USA. [Wolf, Susan M.] NHGRI, Bethesda, MD 20892 USA. RP Wolf, SM (reprint author), Univ Minnesota, Consortium Law & Values Hlth Environm & Life Sci, Minneapolis, MN 55455 USA. FU NHGRI NIH HHS [R01 HG003178, 1 R01 HG 003178, R01 HG003178-01A1] NR 75 TC 50 Z9 50 U1 4 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM PY 2008 VL 36 IS 2 BP 361 EP + DI 10.1111/j.1748-720X.2008.00281.x PG 24 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 308SX UT WOS:000256411400017 PM 18547206 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI Cytokines and fibrocyte differentiation - altering the balance: an interview with Dr. Darrell Pilling SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 0 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 JUN 1 PY 2008 VL 83 IS 6 BP 1334 EP 1335 DI 10.1189/jlb.1307782 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NV UT WOS:000258019800003 PM 18407968 ER PT J AU Chen, KQ Zhang, LZ Huang, J Gong, WH Dunlop, NM Wang, JM AF Chen, Keqiang Zhang, Lingzhi Huang, Jian Gong, Wanghua Dunlop, Nancy M. Wang, Ji Ming TI Cooperation between NOD2 and Toll-like receptor 2 ligands in the up-regulation of mouse mFPR2, a G-protein-coupled A beta(42) peptide receptor, in microglial cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE TLR2; chemotaxis ID AMYLOID-BETA PEPTIDE; MURAMYL DIPEPTIDE; ALZHEIMER-DISEASE; CLEARANCE; FPRL1; TLR; PEPTIDOGLYCAN; INFLAMMATION; ACTIVATION; EXPRESSION AB Human G-protein-coupled formyl peptide receptor-like 1 and its mouse homologue formyl peptide receptor 2 (mFPR2) mediate the chemotactic activity of a variety of pathogen and host-derived peptides, including amyloid beta(42), a key causative factor in Alzheimer's disease. In mouse microglia, mFPR2 is up-regulated by pathogen-associated molecular patterns and proinflammatory cytokines, as shown, for instance, in our previous study using peptidoglycan ( PGN) of Gram(+) bacteria. As PGN and its components have been reported to use TLR2 and an intracellular receptor nucleotide-binding oligomerization domain 2 (NOD2), we investigated the capacity of palmitoyl-cys[(RS)-2,3-di(palmitoyloxy)-propyl]-Ala- Gly-OH (PamCAG), a specific TLR2 ligand, and muramyl dipeptide (MDP), a NOD2 ligand, to cooperatively regulate the expression and function of mFPR2 in microglia. We found that MDP and PamCAG as well as another TLR2-specific agonist palmitoyl-3-cysteine-serine-lysine-4 (Pam3CSK4), when used alone, each increased the expression of functional mFPR2 in microglial cells, and the combination of MDP and PamCAG or Pam3CSK4 exhibited an additive effect. Mechanistic studies revealed that MDP increased the levels of TLR2 expression on the microglial cell surface and enhanced the levels of MAPKs p-38, ERK1/2, and NF-kappa B activated by PamCAG. Our results suggest that TLR2 and NOD2 cooperate to up-regulate the expression of mFPR2 and therefore, may actively participate in the pathogenic processes of brain inflammation and neurodegenerative diseases. C1 [Chen, Keqiang; Zhang, Lingzhi; Huang, Jian; Dunlop, Nancy M.; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Chen, Keqiang] Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 200030, Peoples R China. [Gong, Wanghua] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Bldg 560,Room 31-76, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 34 TC 23 Z9 24 U1 0 U2 2 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 JUN 1 PY 2008 VL 83 IS 6 BP 1467 EP 1475 DI 10.1189/jlb.0907607 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NV UT WOS:000258019800020 PM 18299458 ER PT J AU Christian, TF Aletras, AH Arai, AE AF Christian, Timothy F. Aletras, Anthony H. Arai, Andrew E. TI Estimation of absolute myocardial blood flow during first-pass MR perfusion imaging using a dual-bolus injection technique: Comparison to single-bolus injection method SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI perfusion; hyperemia; adenosine; myocardial blood flow; imaging ID MAGNETIC-RESONANCE; CORONARY-ANGIOGRAPHY; GRADIENT-ECHO; TRANSIT-TIME; RESERVE; QUANTIFICATION; DECONVOLUTION; TOMOGRAPHY; VALIDATION; MODEL AB Purpose: To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF). Materials and Methods: Dogs had local hyperemia. of MBF in the left anterior descending (LAD) coronary artery (intra-coronary adenosine). Animals (n = 6) had sequential single-and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROT). Results: Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROT was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion. Conclusion: Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results. C1 [Christian, Timothy F.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05495 USA. [Aletras, Anthony H.; Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Christian, TF (reprint author), Univ Vermont, Coll Med, Dept Med, 111 Colchester Ave,MCHV McClure 1060, Burlington, VT 05495 USA. EM Timothy.christian@uvm.edu OI Aletras, Anthony/0000-0002-3786-3817 NR 23 TC 45 Z9 45 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2008 VL 27 IS 6 BP 1271 EP 1277 DI 10.1002/jmri.21383 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 307OH UT WOS:000256327700010 PM 18421683 ER PT J AU Abbasi, A Chen, HC Nunamaker, JF AF Abbasi, Ahmed Chen, Hsinchun Nunamaker, Jay F., Jr. TI Stylometric Identification in Electronic Markets: Scalability and Robustness SO JOURNAL OF MANAGEMENT INFORMATION SYSTEMS LA English DT Article DE anti-aliasing; electronic markets; online trust; similarity detection; stylometry ID GROUP SUPPORT-SYSTEMS; AUTHORSHIP IDENTIFICATION; REPUTATION SYSTEMS; ONLINE; ATTRIBUTION; MECHANISMS; MESSAGES; INTERNET; TRUST AB Online reputation systems are intended to facilitate the propagation of word of mouth as a credibility scoring mechanism for improved trust in electronic marketplaces. However, they experience two problems attributable to anonymity abuse-easy identity changes and reputation manipulation. In this study, we propose the use of stylometric analysis to help identify online traders based on the writing style traces inherentin their posted feedback comments. We incorporated a rich stylistic feature set and developed the Writeprint technique for detection of anonymous trader identities. The technique and extended feature set were evaluated on a test bed encompassing thousands of feedback comments posted by 200 eBay traders. Experiments conducted to assess the scalability (number of traders) and robustness (against intentional obfuscation) of the proposed approach found it to significantly outperform benchmark stylometric techniques. The results indicate that the proposed method may help militate against easy identity changes and reputation manipulation in electronic markets. C1 [Abbasi, Ahmed] Univ Wisconsin, Sheldon B Lubar Sch Business, Milwaukee, WI 53201 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Univ Arizona, MIS, Tucson, AZ USA. [Chen, Hsinchun] Univ Arizona, Ctr Management Informat, Tucson, AZ USA. RP Abbasi, A (reprint author), Univ Wisconsin, Sheldon B Lubar Sch Business, Milwaukee, WI 53201 USA. FU NSF Information and Data Management Program, "Multilingual Online Stylometric Authorship Identification: An Exploratory Study," [8/2006-8/2007] FX This research was funded in part by the following grant: NSF Information and Data Management Program, "Multilingual Online Stylometric Authorship Identification: An Exploratory Study," 8/2006-8/2007. NR 49 TC 19 Z9 19 U1 1 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0742-1222 EI 1557-928X J9 J MANAGE INFORM SYST JI J. Manage. Inform. Syst. PD SUM PY 2008 VL 25 IS 1 BP 49 EP 78 DI 10.2753/MIS0742-1222250103 PG 30 WC Computer Science, Information Systems; Information Science & Library Science; Management SC Computer Science; Information Science & Library Science; Business & Economics GA 335IF UT WOS:000258283300004 ER PT J AU Strech, D Synofzik, M Marckmann, G AF Strech, D. Synofzik, M. Marckmann, G. TI Systematic reviews of empirical bioethics SO JOURNAL OF MEDICAL ETHICS LA English DT Review ID QUALITATIVE RESEARCH; SCARCE RESOURCES; DECISION-MAKING; HEALTH-CARE; PHYSICIANS; RECOMMENDATIONS; ATTITUDES; BARRIERS; BEDSIDE; SEARCH AB Background: Publications and discussions of survey research in empirical bioethics have steadily increased over the past two decades. However, findings often differ among studies with similar research questions. As a consequence, ethical reasoning that considers only parts of the existing literature and does not apply systematic reviews tends to be biased. To date, we lack a systematic review (SR) methodology that takes into account the specific conceptual and practical challenges of empirical bioethics. Methods: The steps of systematically reviewing empirical findings in bioethics are presented and critically discussed. In particular, (a) the limitations of traditional SR methodologies in the field of empirical bioethics are critically discussed, and (b) conceptual and practical recommendations for SRs in empirical bioethics that are (c) based on the authors' review experiences in healthcare ethics are presented. Results: A 7-step approach for SRs of empirical bioethics is proposed: (1) careful definition of review question; (2) selection of relevant databases; (3) application of ancillary search strategies; (4) development of search algorithms; (5) relevance assessment of the retrieved references; (6) quality assessment of included studies; and (7) data analysis and presentation. Conceptual and practical challenges arise because of various peculiarities in reviewing empirical bioethics literature and can lead to biased results if they are not taken into account. Conclusions: If suitably adapted to the peculiarities of the field, SRs of empirical bioethics provide transparent information for ethical reasoning and decision-making that is less biased than single studies. C1 [Strech, D.; Synofzik, M.; Marckmann, G.] Univ Tubingen, Inst Eth & Geschichte Med, D-72076 Tubingen, Germany. [Strech, D.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Synofzik, M.] Univ Tubingen, Hertie Inst Clin Brain Res, Ctr Neurol, Tubingen, Germany. RP Strech, D (reprint author), Univ Tubingen, Inst Eth & Geschichte Med, Schleichstr 8, D-72076 Tubingen, Germany. EM strech@uni-tuebingen.de OI Strech, Daniel/0000-0002-9153-079X NR 34 TC 22 Z9 22 U1 1 U2 11 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JUN PY 2008 VL 34 IS 6 BP 472 EP 477 DI 10.1136/jme.2007.021709 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 307BV UT WOS:000256293600014 PM 18511623 ER PT J AU Toro, JR Wei, MH Glenn, GM Weinreich, M Toure, O Vocke, C Turner, M Choyke, P Merino, MJ Pinto, PA Steinberg, SM Schmidt, LS Linehan, WM AF Toro, J. R. Wei, M-H Glenn, G. M. Weinreich, M. Toure, O. Vocke, C. Turner, M. Choyke, P. Merino, M. J. Pinto, P. A. Steinberg, S. M. Schmidt, L. S. Linehan, W. M. TI BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID RENAL-CELL CANCER; TUMOR-SUPPRESSOR GENE; GERMAN-SHEPHERD DOG; NIHON RAT MODEL; SPONTANEOUS PNEUMOTHORAX; HEREDITARY LEIOMYOMATOSIS; NODULAR DERMATOFIBROSIS; INTESTINAL POLYPOSIS; KIDNEY NEOPLASIA; LUNG CYSTS AB Background: Birt-Hogg-Dube syndrome (BHDS) (MIM 135150) is an autosomal dominant predisposition to the development of follicular hamartomas (fibrofolliculomas), lung cysts, spontaneous pneumothorax, and kidney neoplasms. Germline mutations in BHD are associated with the susceptibility for BHDS. We previously described 51 BHDS families with BHD germline mutations. Objective: To characterise the BHD mutation spectrum, novel mutations and new clinical features of one previously reported and 50 new families with BHDS. Methods: Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning. We analysed evolutionary conservation of folliculin by comparing human against the orthologous sequences. Results: The BHD mutation detection rate was 88% (51/58). Of the 23 different germline mutations identified, 13 were novel consisting of: four splice site, three deletions, two insertions, two nonsense, one deletion/insertion, and one missense mutation. We report the first germline missense mutation in BHD c. 1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas. This mutation occurs in a highly conserved amino acid in folliculin. 10% (5/51) of the families had individuals without histologically confirmed fibrofolliculomas. Of 44 families ascertained on the basis of skin lesions, 18 (41%) had kidney tumours. Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p = 0.0032). Similarly, patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased greater probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p = 0.011). A comprehensive review of published reports of cases with BHD germline mutation is discussed. Conclusion: BHDS is characterised by a spectrum of mutations, and clinical heterogeneity both among and within families. C1 [Toro, J. R.; Wei, M-H; Glenn, G. M.; Weinreich, M.; Toure, O.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Wei, M-H; Schmidt, L. S.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. [Vocke, C.; Pinto, P. A.; Schmidt, L. S.; Linehan, W. M.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Turner, M.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Choyke, P.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Merino, M. J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Plaza S,Room 7012, Bethesda, MD 20892 USA. EM torojo@mail.nih.gov FU Intramural NIH HHS [Z01 SC006659-25]; NCI NIH HHS [N01 CO012400, N01-CO-12400., N01CO12400] NR 46 TC 174 Z9 177 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 2008 VL 45 IS 6 BP 321 EP 331 DI 10.1136/jmg.2007.054304 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 308DW UT WOS:000256369500001 PM 18234728 ER PT J AU Kirkwood, CD Boniface, K Richardson, S Taraporewala, ZF Patton, JT Bishop, RF AF Kirkwood, Carl D. Boniface, Karen Richardson, Simone Taraporewala, Zenobia F. Patton, John T. Bishop, Ruth F. TI Non-structural protein NSP2 induces heterotypic antibody responses during primary rotavirus infection and reinfection in children SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE rotavirus; NSP2; humoral immune responses; enzyme immunoassay ID YOUNG-CHILDREN; NATURAL INFECTION; SERUM ANTIBODIES; PROTECTION; GASTROENTERITIS; REPLICATION; EFFICACY; DIARRHEA; IMMUNITY; DISEASE AB Rotaviruses are the single most important causes of severe acute diarrhoea in children worldwide. Despite success in developing vaccines, there is still a lack of knowledge about many components of the immune response, particularly those to non-structural proteins. This study established radioimmunoprecipitation (RIP) assays using labeled G1P[8], G2P[4], and G4P[6] human rotaviruses to examine the spectrum and duration of rotavirus antibodies in sera collected sequentially for 18-36 months from 27 children after hospitalization for primary rotavirus gastroenteritis. Five children experienced rotavirus re-infections. Primary responses detected to non-structural protein NSP2 declined to baseline after 100-150 days. Responses were heterotypic between NSP2 of G1P[81 and G4P[81 rotaviruses. Re-infections after 465-786 days boosted antibody levels to NSP2 of both serotypes, together with the appearance of anti-NSP2 to G2P[41, even though there was no evidence of infection with this serotype. We developed an enzymeimmunoassay to measure sequential levels of anti-NSP2 IgG and IgA, using recombinant (heterotypic) NSP2 derived from SA11 (G3P[21). Anti-NSP2 IgG and IgA were detected in sera from 23/23 (100%) and 18/24 (75%) of children after primary infection, declined to baseline after 100-150 days, were boosted after rotavirus re-infections, and again declined to baseline 150 days later. Anti-NSP2 IgA was also detected after primary infection, in duodenal juice from 14/16 (87%), and faecal extract from 11/19 (57%) of children. Sequential estimation of anti-NSP2 EIA levels in sera could be a sensitive index of rotavirus infection and re-infection. The potential of anti-NSP2 to limit viral replication after reinfection deserves further study. C1 [Kirkwood, Carl D.; Boniface, Karen; Richardson, Simone; Bishop, Ruth F.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Enter Viros Res Grp, Melbourne, Vic, Australia. [Kirkwood, Carl D.; Boniface, Karen; Richardson, Simone; Bishop, Ruth F.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Taraporewala, Zenobia F.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kirkwood, CD (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Enter Viros Res Grp, 8th Floor AP Bldg,Room SW834,Flemington Rd, Parkville, Vic 3052, Australia. EM carl.kirkwood@mcri.edu.au RI Patton, John/P-1390-2014 FU Intramural NIH HHS [Z01 AI000754-12] NR 30 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0146-6615 EI 1096-9071 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2008 VL 80 IS 6 BP 1090 EP 1098 DI 10.1002/jmv.21160 PG 9 WC Virology SC Virology GA 293AP UT WOS:000255307500024 PM 18428132 ER PT J AU Chen, RB Holmes, EC AF Chen, Rubing Holmes, Edward C. TI The evolutionary dynamics of human influenza B virus SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE influenza B virus; phylogeny; reassortment; coalescent; antigenic drift; epidemiology ID PHYLOGENETIC ANALYSIS; RNA VIRUSES; COCIRCULATING LINEAGES; FREQUENT REASSORTMENT; HEMAGGLUTININ GENE; A VIRUSES; RATES; INTERFERENCE; TRANSMISSION; SUBSTITUTION AB Despite their close phylogenetic relationship, type A and B influenza viruses exhibit major epidemiological differences in humans, with the latter both less common and less often associated with severe disease. However, it is unclear what processes determine the evolutionary dynamics of influenza B virus, and how influenza viruses A and B interact at the evolutionary scale. To address these questions we inferred the phylogenetic history of human influenza B virus using complete genome sequences for which the date (day) of isolation was available. By comparing the phylogenetic patterns of all eight viral segments we determined the occurrence of segment reassortment over a 30-year sampling period. An analysis of rates of nucleotide substitution and selection pressures revealed sporadic occurrences of adaptive evolution, most notably in the viral hemagglutinin and compatible with the action of antigenic drift, yet lower rates of overall and nonsynonymous nucleotide substitution compared to influenza A virus. Overall, these results led us to propose a model in which evolutionary changes within and between the antigenically distinct 'Yam88' and 'Vic87' lineages of influenza B virus are the result of changes in herd immunity, with reassortment continuously generating novel genetic variation. Additionally, we suggest that the interaction with influenza A virus may be central in shaping the evolutionary dynamics of influenza B virus, facilitating the shift of dominance between the Vic87 and the Yam88 lineages. C1 [Chen, Rubing; Holmes, Edward C.] Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM ech15@psu.edu RI Chen, Rubing/F-2314-2011; Chen, Rubing/A-2276-2010; OI Holmes, Edward/0000-0001-9596-3552 FU NIGMS NIH HHS [GM080533-01, R01 GM080533, R01 GM080533-02] NR 37 TC 82 Z9 89 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD JUN PY 2008 VL 66 IS 6 BP 655 EP 663 DI 10.1007/s00239-008-9119-z PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 322RK UT WOS:000257392800012 PM 18504518 ER PT J AU Sommer, WH Saavedra, JM AF Sommer, Wolfgang H. Saavedra, Juan M. TI Targeting brain angiotensin and corticotrophin-releasing hormone systems interaction for the treatment of mood and alcohol use disorders SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE angiotensin receptor; ACE; alcoholism; anxiety; gene expression ID ISOLATION STRESS; CRF1 RECEPTOR; ANIMAL-MODELS; RATS; ANTAGONIST; ETHANOL; DEPENDENCE; NEUROBIOLOGY; SENSITIVITY; CONSUMPTION AB The brain renin-angiotensin system (RAS) participates importantly in the regulation of endocrine, autonomic, and behavioral response to stress. Recent data indicate that central action of AT(1) receptor antagonists can reduce anxiety symptoms in experimental animals. Furthermore, central inhibition of RAS activity decreases ethanol intake in an animal model of alcoholism. Pathological anxiety responses and the development of substance dependence are both critically mediated through corticotrophin-releasing hormone (CRH) systems, and the RAS is positioned to interact both with hypothalamic as well as extrahypothalamic CRH systems. The thesis of this paper is that the RAS is part of the neurochemical dysregulation underlying negative affective states, anxiety disorders, and ethanol dependence and that medications targeting the RAS should be considered to augment the treatment of these disorders. C1 [Sommer, Wolfgang H.] NCI, NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Saavedra, Juan M.] NIMH, NIH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Sommer, WH (reprint author), NCI, NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,B 10,R 15330, Bethesda, MD 20892 USA. EM wolfgang.sommer@mail.nih.gov OI Sommer, Wolfgang/0000-0002-5903-6521 FU Intramural NIH HHS [Z99 MH999999] NR 35 TC 11 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD JUN PY 2008 VL 86 IS 6 BP 723 EP 728 DI 10.1007/s00109-008-0333-3 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 299HO UT WOS:000255746900020 PM 18449521 ER PT J AU Lan, MJ Yuan, PX Chen, G Manji, HK AF Lan, Martin J. Yuan, Peixiong Chen, Guang Manji, Husseini K. TI Neuronal peroxisome proliferator-activated receptor gamma signaling: Regulation by mood-stabilizer valproate SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE valproate; bipolar disorder; epilepsy; PPAR gamma; metabolism ID GLYCOGEN-SYNTHASE KINASE-3; TRANSIENT FOCAL ISCHEMIA; ARACHIDONIC-ACID; BIPOLAR DISORDER; SODIUM-VALPROATE; BETA-OXIDATION; PPAR-GAMMA; RAT-BRAIN; 15D-PROSTAGLANDIN J(2); HISTONE DEACETYLASE AB Valproate (Depakote) remains an effective medication for the prevention and treatment of seizures in epilepsy and of mood symptoms in bipolar disorder. Both of these disorders are severe and debilitating, and both warrant further medication options as well as a better understanding of the side effects associated with their current treatments. Although a number of molecular and cellular processes have been found to be altered by valproate, the medication's therapeutic mechanism has not been fully elucidated. In this paper, peroxisome proliferator-activated receptor (PPAR) signaling was examined to determine valproate's effects on this transcriptional regulatory system in neuronal tissue. PPAR signaling has been found to affect a number of biochemical processes, including lipid metabolism, cellular differentiation, insulin sensitivity, and cell survival. When primary neuronal cultures were treated with valproate, a significant decrease in PPAR gamma signaling was observed. This effect was demonstrated through a change in nuclear quantities of PPAR gamma receptor and decreased DNA binding of the receptor. Valproate also caused gene expression changes and a change to the peroxisome biochemistry consistent with a decrease of PPAR gamma signaling. These biochemical changes may have functional consequences for either valproate's therapeutic mechanism or for its neurological side effects and merit further investigation. C1 [Manji, Husseini K.] Porter Neurosci Res Ctr, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Lan, Martin J.; Yuan, Peixiong; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), Porter Neurosci Res Ctr, Mol Pathophysiol Lab, Bldg 35,Room 1C-917,35 Convent Dr,MSC 3711, Bethesda, MD 20892 USA. EM manji@nih.gov RI Chen, Guang/A-2570-2017 FU Intramural NIH HHS [ZIA MH002921-01] NR 64 TC 10 Z9 10 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JUN PY 2008 VL 35 IS 2 BP 225 EP 234 DI 10.1007/s12031-008-9056-8 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 307TO UT WOS:000256341400010 PM 18437585 ER PT J AU Kamal, MA Qu, XQ Yu, QS Tweedie, D Holloway, HW Li, YZ Tan, Y Greig, NH AF Kamal, Mohammad A. Qu, Xianqin Yu, Qian-sheng Tweedie, David Holloway, Harold W. Li, Yazhou Tan, Yi Greig, Nigel H. TI Tetrahydrofurobenzofuran cymserine, a potent butyrylcholinesterase inhibitor and experimental Alzheimer drug candidate, enzyme kinetic analysis SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE acetylcholinesterase; Alzheimer's disease; anticholinesterase; bisnorcymserine; butyrylcholinestrase; cymserine; enzyme inhibition kinetics; tetrahydrofurobenzofuran ID KNOCKOUT MICE; DISEASE; ACETYLCHOLINESTERASE; BETA; DONEPEZIL; DEMENTIA; THERAPY; METHANOBENZODIOXEPINE; PHENSERINE; PEPTIDE AB Synaptic loss, particularly related to the forebrain cholinergic system, is considered to be an early event that leads to Alzheimer's disease (AD) and has led to the development of acetylcholinesterase inhibitors (AChE-Is) as the mainstay of treatment for several degenerative disorders that culminate in dementia. The primary dose-limiting toxicities of all clinically available AChE-Is are, similar to useful actions on cognition, cholinergically mediated and they ultimately limit the value of this drug class in achieving anything but symptomatic improvements. In addition, AChE levels in brain areas associated with AD decline with disease progression, which likely ultimately limits the therapeutic utility of this drug class. New research indicates that selective inhibition of butyrylcholinesterase (BuChE), a closely related enzyme that is markedly elevated in AD brain, increases acetylcholine (ACh) and augments cognition in rodents free of the characteristic undesirable actions of AChE-Is. BuChE inhibition hence represents an innovative treatment approach for AD, and agents are currently being synthesized to optimally achieve this. The novel compound, tetrahydrofurobenzofuran cymserine (THFBFC), is derived from our effort to produce a potent and BuChE-selective inhibitor as a candidate to test the hypothesis that BuChE-Is would be efficacious and better tolerated than AChE-Is in AD. Herein, we applied innovative enzyme kinetic analyses to characterize the quantitative interaction of THFBFC with human BuChE. These provided values for the agent's IC50, together with specific new kinetic constants, such as K (T50), K (T1/2), R (I), K-o (RT), P-o (max), K (PT) and PT1/2, to aid define target concentrations for clinical translation. Additional classical kinetic parameters, including K (i), K (m) or K (s), k (cat) or V (max) and V (mi) were also determined. THFBFC proved to be a potent competitive inhibitor of human BuChE and, like its isomer dihydrobenzodioxepine cymserine, is a potentially interesting AD drug candidate. C1 [Kamal, Mohammad A.; Qu, Xianqin; Tan, Yi] Univ Technol Sydney, Fac Sci, Dept Med & Mol BioSci, Sydney, NSW 2007, Australia. [Yu, Qian-sheng; Tweedie, David; Holloway, Harold W.; Li, Yazhou; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Lab Neurosci, Intramural Res Program,NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Kamal, MA (reprint author), Univ Technol Sydney, Fac Sci, Dept Med & Mol BioSci, POB 123, Sydney, NSW 2007, Australia. EM Mohammad.Kamal@uts.edu.au; Greign@grc.nia.nih.gov RI Kamal, Mohammad/H-9643-2012; Kamal, Mohammad/J-4622-2013; OI Kamal, Mohammad/0000-0003-1862-173X; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU Intramural NIH HHS [, Z01 AG000311-08] NR 52 TC 29 Z9 30 U1 0 U2 3 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 EI 1435-1463 J9 J NEURAL TRANSM JI J. Neural Transm. PD JUN PY 2008 VL 115 IS 6 BP 889 EP 898 DI 10.1007/s00702-008-0022-y PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 309PJ UT WOS:000256472400014 PM 18235987 ER PT J AU Gobbi, M Funicello, M Gerstbrein, K Holy, M Moya, PR Sotomayor, R Forray, MI Gysling, K Paluzzi, S Bonanno, G Reyes-Parada, M Sitte, HH Mennini, T AF Gobbi, Marco Funicello, Marcella Gerstbrein, Klaus Holy, Marion Moya, Pablo R. Sotomayor, Ramon Forray, Maria Ines Gysling, Katia Paluzzi, Silvio Bonanno, Giambattista Reyes-Parada, Miguel Sitte, Harald H. Mennini, Tiziana TI N,N-dimethyl-thioamphetamine and methyl-thioamphetamine, two non-neurotoxic substrates of 5-HT transporters, have scant in vitro efficacy for the induction of transporter-mediated 5-HT release and currents SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE methyl-thioamphetamine; NN-dimethyl-thioamphetamine; neurotoxicity; p-Cl-amphetamine; serotonin release; serotonin transporters ID DOPAMINE RELEASE; LATERAL SEPTUM; SEROTONERGIC PROJECTIONS; AMPHETAMINE DERIVATIVES; P-METHYLTHIOAMPHETAMINE; RAT-BRAIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; VIVO; 1-(M-CHLOROPHENYL)PIPERAZINE; NEUROTRANSMITTERS AB We studied two non-neurotoxic amphetamine derivatives (methyl-thioamphetamine, MTA and NN-dimethylMTA, DMMTA) interacting with serotonin (5-HT) transporters (SERTs) with affinities comparable to that of p-Cl-amphetamine (pCA). The rank order for their maximal effects in inducing both [(3)H]5-HT release from rat brain synaptosomes or hSERT-expressing HEK-293 cells, and currents in hSERT-expressing oocytes, was pCA >> MTA >= DMMTA. A correlation between drug-induced release and currents is also strengthened by the similar bell shape of the dose-response curves. Release experiments indicated that MTA and DMMTA are SERT substrates although MTA is taken up by HEK-293 cells with a V(max) 40% lower than pCA. The weak effects of MTA and DMMTA in vitro might therefore be due to their properties as 'partial substrates' on the mechanisms, other than translocation, responsible for currents and/or release. After either local or systemic in vivo administration, MTA and DMMTA release 5-HT in a manner comparable to pCA. These findings confirm that the neurotoxic properties of some amphetamine derivatives are independent of their 5-HT-releasing activity in vivo. It is worth noting that only those amphetamine derivatives with high efficiency in inducing 5-HT release and currents in vitro have neurotoxic properties. C1 [Gobbi, Marco; Funicello, Marcella; Mennini, Tiziana] Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, I-20156 Milan, Italy. [Gerstbrein, Klaus; Holy, Marion; Sitte, Harald H.] Med Univ Vienna, Inst Pharmacol, Vienna, Austria. [Moya, Pablo R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Sotomayor, Ramon; Forray, Maria Ines; Gysling, Katia] Catholic Univ Chile, Fac Biol Sci, Dept Cellular & Mol Biol, Santiago, Chile. [Paluzzi, Silvio; Bonanno, Giambattista] Univ Genoa, Sect Pharmacol & Toxicol, Dept Expt Med, I-16126 Genoa, Italy. [Paluzzi, Silvio; Bonanno, Giambattista] Univ Genoa, Ctr Excellence Biomed Res, I-16126 Genoa, Italy. [Reyes-Parada, Miguel] Univ Santiago Chile, Fac Med Sci, Santiago, Chile. [Reyes-Parada, Miguel] Millennium Inst Cell Dynam & Biotechnol, Santiago, Chile. RP Gobbi, M (reprint author), Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, Via Masa 19, I-20156 Milan, Italy. EM Gobbi@marionegri.it RI Bonanno, Giambattista/C-5856-2008; Sitte, Harald/N-2681-2013; Gobbi, Marco/J-2638-2016; OI Sitte, Harald/0000-0002-1339-7444; Gobbi, Marco/0000-0003-1014-6225; Bonanno, Giambattista/0000-0003-3744-5786 FU Austrian Science Fund FWF [P 18706] NR 41 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2008 VL 105 IS 5 BP 1770 EP 1780 DI 10.1111/j.1471-4159.2008.05272.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 300OQ UT WOS:000255835000018 PM 18248615 ER PT J AU Graham, DL Noailles, PAH Cadet, JL AF Graham, Devon L. Noailles, Pierre-A. H. Cadet, Jean Lud TI Differential neurochemical consequences of an escalating dose-binge regimen followed by single-day multiple-dose methamphetamine challenges SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; methamphetamine; serotonin; tolerance; toxicity; turnover ID INDUCED NEURONAL APOPTOSIS; SUBSTITUTED AMPHETAMINES; STRIATAL DOPAMINE; ABSTINENT METHAMPHETAMINE; ENVIRONMENTAL-TEMPERATURE; MICROGLIAL ACTIVATION; INDUCED NEUROTOXICITY; BRAIN CATECHOLAMINES; TRANSPORTER DENSITY; MONOAMINE-OXIDASE AB Chronic intake of methamphetamine (METH) causes tolerance to its behavioral and subjective effects. To better mimic human patterns of drug abuse, the present study used a rodent model that took into account various facets of human drug administration and measured METH-induced effects on brain monoamine levels. Adult male Sprague-Dawley rats were injected with METH or saline according to an escalating dose schedule for 2 weeks. This was followed by a challenge regimen of either saline or one of two doses of METH (3 x 10 mg/kg every 2 h or 6 x 5 mg/kg given every hour, both given within a single day). Both challenge doses of METH caused significant degrees of depletion of clopamine in the striatum and norepinephrine and serotonin in the striatum, cortex, and hippocampus. Animals pre-treated with METH showed significant attenuation of METH-induced striatal dopamine depletion but not consistent attenuation of norepinephrine and serotonin depletion. Unexpectedly, METH pre-treated animals that received the 3 x 10 mg/kg challenge showed less increases in tympanic temperatures than saline pre-treated rats whereas METH pre-treated animals that received the 6 x 5 mg/kg METH challenge showed comparable increases in temperatures to saline pre-treated rats. Therefore, pre-treatment-induced partial protection against monoamine depletion is probably not because of attenuated METH-induced hyperthermia in those rats. C1 [Graham, Devon L.; Noailles, Pierre-A. H.; Cadet, Jean Lud] NIDA, DHHS, Mol Neuropsychiat Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. [Graham, Devon L.] Univ Maryland, Sch Med, Toxicol Program, Baltimore, MD 21201 USA. RP Cadet, JL (reprint author), NIDA, DHHS, Mol Neuropsychiat Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov OI Graham, Devon/0000-0003-0318-4602 FU Intramural NIH HHS NR 59 TC 30 Z9 30 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2008 VL 105 IS 5 BP 1873 EP 1885 DI 10.1111/j.1471-4159.2008.05269.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 300OQ UT WOS:000255835000026 PM 18248616 ER PT J AU Guilarte, TR Burton, NC Verina, T Prabhu, VV Beckert, KG Syversen, T Schneider, JS AF Guilarte, Tomas R. Burton, Neal C. Verina, Tatyana Prabhu, Vinaykumar V. Beckert, Kevin G. Syversen, Tore Schneider, Jay S. TI Increased APLP1 expression and neurodegeneration in the frontal cortex of manganese-exposed non-human primates SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyloid-beta; amyloid-beta precursor-like protein 1; manganese; neurodegeneration; non-human; primates; p53 ID PRECURSOR-LIKE PROTEIN-1; NEURONAL CELL-DEATH; FACTOR NF-Y; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; CEREBRAL-CORTEX; TARGET GENE; DNA-BINDING; P53; BETA AB Chronic manganese (Mn) exposure produces a neurological syndrome with psychiatric, cognitive, and parkinsonian features. Gene expression profiling in the frontal cortex of Cynomologous macaques receiving 3.3-5.0 mg Mn/kg weekly for 10 months showed that 61 genes were increased and four genes were decreased relative to controls from a total of 6766 genes. Gene changes were associated with cell cycle regulation, DNA repair, apoptosis, ubiquitin-proteasome system, protein folding, cholesterol homeostasis, axonal/vesicular transport, and inflammation. Amyloid-beta (A beta) precursor-like protein 1, a member of the amyloid precursor protein family, was the most highly up-regulated gene. Immunohistochemistry confirmed increased amyloid precursor-like protein 1 protein expression and revealed the presence of diffuse A beta plaques in Mn-exposed frontal cortex. Cortical neurons and white matter fibers from Mn-exposed animals accumulated silver grains indicative of on-going degeneration. Cortical neurons also exhibited nuclear hypertrophy, intracytoplasmic vacuoles, and apoptosis stigmata. p53 immunolabeling was increased in the cytoplasm of neurons and in the nucleus and processes of glial cells in Mn-exposed tissue. In summary, chronic Mn exposure produces a cellular stress response leading to neurodegenerative changes and diffuse A beta plaques in the frontal cortex. These changes may explain the subtle cognitive deficits previously demonstrated in these same animals. C1 [Guilarte, Tomas R.; Burton, Neal C.; Verina, Tatyana] Johns Hopkins Univ, Clin Teaching Block, Bloomberg Sch Publ Hlth,Dept Environm Hlth Sci, Neurotoxicol & Mol Imaging Lab, Baltimore, MD 21205 USA. [Prabhu, Vinaykumar V.; Beckert, Kevin G.] NIA, Gene Express & Genom Unit, Baltimore, MD 21224 USA. [Syversen, Tore] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Schneider, Jay S.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Guilarte, TR (reprint author), Johns Hopkins Univ, Clin Teaching Block, Bloomberg Sch Publ Hlth,Dept Environm Hlth Sci, Neurotoxicol & Mol Imaging Lab, 615 N Wolfe St,Room E6622, Baltimore, MD 21205 USA. EM tguilart@jhsph.edu OI Becker, Kevin/0000-0002-6794-6656 FU NIEHS NIH HHS [ES010975, R01 ES010975, R56 ES010975, T32 ES007141, T32 ES07141] NR 72 TC 58 Z9 58 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2008 VL 105 IS 5 BP 1948 EP 1959 DI 10.1111/j.1471-4159.2008.05295.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 300OQ UT WOS:000255835000032 PM 18284614 ER PT J AU Fotheringham, J Williams, EL Akhyani, N Jacobson, S AF Fotheringham, Julie Williams, Elizabeth L. Akhyani, Nahid Jacobson, Steven TI Human herpesvirus 6 (HHV-6) induces dysregulation of glutamate uptake and transporter expression in astrocytes SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article DE human herpesvirus 6; neurologic disease; human astrocytes ID TEMPORAL-LOBE EPILEPSY; MULTIPLE-SCLEROSIS LESIONS; HUMAN HERPESVIRUS-6; CEREBROSPINAL-FLUID; GENE-EXPRESSION; HUMAN BRAIN; VARIANT-A; T-CELLS; INFECTION; HIPPOCAMPUS AB Human herpesvirus 6 (HHV-6) infects and establishes latency in the central nervous system (CNS). Reactivation of latent HHV-6 has been associated with neurologic diseases including epilepsy and multiple sclerosis (MS). In vivo, HHV-6 has been localized to astrocytes and can infect human astrocytes in vitro, suggesting that this virus may have a tropism for glial cells and may affect glial cell function. An essential role of astrocytes in the CNS is active maintenance of the excitatory neurotransmitter glutamate. Dysregulation of glutamate has been implicated as a potential mechanism of disease in both epilepsy and MS. Both disorders have demonstrated elevated glutamate in CSF and may be associated with dysregulation of glutamate signaling, uptake, and metabolism. This study demonstrates dysregulation of glutamate uptake in human astrocytes infected with both variants of HHV-6, A and B, with differential effects of HHV-6 in acute and persistently infected cells. Whereas astrocytes acutely infected with HHV-6 demonstrated increased glutamate uptake, cells persistently infected with HHV-6A and HHV-6B demonstrated impaired glutamate uptake. Functional dysregulation of glutamate uptake was associated with early increases in mRNA and protein expression of the glial glutamate transporter EAAT-2 followed by a sustained decrease in mRNA expression in astrocytes infected with both HHV-6A and HHV-6B. Dysregulated glutamate uptake and transporter expression suggests a mechanism for dysregulation of glutamate levels in vivo and a potential mechanism for virus-associated neurologic disease. C1 [Fotheringham, Julie; Williams, Elizabeth L.; Akhyani, Nahid; Jacobson, Steven] NINDS, NIH, Virol Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, NIH, Virol Immunol Sect, Neuroimmunol Branch, 9000 Rockville Pike,Bldg 10,Rm 5Bb16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 47 TC 14 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD JUN PY 2008 VL 3 IS 2 BP 105 EP 116 DI 10.1007/s11481-007-9084-0 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 299JV UT WOS:000255752800007 PM 18247129 ER PT J AU Sander, T Sprenger, A Neumann, G Gottschalk, S Machner, B Helmchen, C Rambold, H AF Sander, T. Sprenger, A. Neumann, G. Gottschalk, S. Machner, B. Helmchen, C. Rambold, H. TI Vergence deficits in cerebellar lesions SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 18th Meeting of the European-Neurological-Society CY JUN 07-11, 2008 CL Nice, FRANCE SP European Neurolog Soc C1 Med Univ Lubeck, D-23538 Lubeck, Germany. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2008 VL 255 SU 2 MA O174 BP 41 EP 41 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 299HP UT WOS:000255747000140 ER PT J AU Hartung, HP Bril, V Dalakas, M Deng, C Donofrio, P Hanna, K Hughes, R Latov, N Merkies, I van Doorn, P AF Hartung, H-P. Bril, V. Dalakas, M. Deng, C. Donofrio, P. Hanna, K. Hughes, R. Latov, N. Merkies, I. van Doorn, P. TI Short-term and long-term efficacy of immune globulin intravenous, 10% caprylate/chromatography purified for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 18th Meeting of the European-Neurological-Society CY JUN 07-11, 2008 CL Nice, FRANCE SP European Neurolog Soc C1 Univ Dusseldorf, Dusseldorf, Germany. Univ Hlth Network, Toronto, ON, Canada. Natl Inst Hlth, Bethesda, MD USA. Talecris Biotherapeut, Res Triangle Pk, NC USA. Vanderbilt Univ, Nashville, TN USA. Kings Coll London, Guys Hosp, London WC2R 2LS, England. Cornell Univ, New York, NY 10021 USA. Erasmus MC, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2008 VL 255 SU 2 MA P427 BP 106 EP 106 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 299HP UT WOS:000255747000391 ER PT J AU Bril, V Katzberg, H Dalakas, M Deng, C Donofrio, P Hanna, K Hartung, HP Hughes, R Latov, N Merkies, I van Doorn, P AF Bril, V. Katzberg, H. Dalakas, M. Deng, C. Donofrio, P. Hanna, K. Hartung, H-P. Hughes, R. Latov, N. Merkies, I. van Doorn, P. TI Changes in electrophysiology in patients with chronic inflammatory demyelinating polyneuropathy treated with immune globulin intravenous, 10% caprylate/chromatography purified versus placebo for up to 24 weeks SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 18th Meeting of the European-Neurological-Society CY JUN 07-11, 2008 CL Nice, FRANCE SP European Neurol Soc C1 Univ Hlth Network, Toronto, ON, Canada. Stanford Univ, Palo Alto, CA 94304 USA. NIH, Bethesda, MD 20892 USA. Talecris Biotherapeut, Res Triangle Pk, NC USA. Vanderbilt Univ, Nashville, TN USA. Heinrich Heine Univ, Dusseldorf, Germany. Kings Coll London, Guys Hosp, London, England. Cornell Univ, New York, NY 10021 USA. Erasmus MC, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2008 VL 255 SU 2 MA P439 BP 109 EP 109 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 299HP UT WOS:000255747000403 ER PT J AU Rueger, MA Munasinghe, JP Koretsky, AP Mckay, RD AF Rueger, M. A. Munasinghe, J. P. Koretsky, A. P. Mckay, R. D. TI Characterisation of the 6-OHDA model of Parkinson's disease using manganese-enhanced MRI SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 18th Meeting of the European-Neurological-Society CY JUN 07-11, 2008 CL Nice, FRANCE SP European Neurolog Soc C1 Uniklin Koeln, Cologne, Germany. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2008 VL 255 SU 2 MA P672 BP 167 EP 167 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 299HP UT WOS:000255747000633 ER PT J AU Iacono, D O'Brien, R Resnick, SM Zonderman, AB Pletnikova, O Rudow, G An, Y West, MJ Crain, B Troncoso, JC AF Iacono, Diego O'Brien, Richard Resnick, Susan M. Zonderman, Alan B. Pletnikova, Olga Rudow, Gay An, Yang West, Mark J. Crain, Barbara Troncoso, Juan C. TI Neuronal hypertrophy in asymptomatic Alzheimer disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE beta-amyloid; Alzheimer disease pathogenesis; mild cognitive impairment; nuclear hypertrophy; nucleolar hypertrophy; neuronal resistance; tau ID MILD COGNITIVE IMPAIRMENT; DEMENTED OLD PEOPLE; CINGULATE GYRUS; NEUROCHEMICAL CHANGES; MEDIAL AMYGDALA; ESTROUS-CYCLE; NEUROPATHOLOGY; RESERVE; AD; HIPPOCAMPUS AB The pathologic changes of Alzheimer disease (AD) evolve very gradually over decades before the disease becomes clinically manifest. Thus, it is not uncommon to find substantial numbers of A beta plaques and neurofibrillary tangles in autopsy brains of older subjects with documented normal cognition, a state that we define as asymptomatic AD (ASYMAD). The goal of this study is to understand the morphometric substrate of ASYMAD subjects compared with mild cognitive impairment and definite AD cases. We used designed-based stereology to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in 4 cerebral regions: anterior cingulate gyrus, posterior cingulate gyrus, primary visual cortex, and CA1 of hippocampus. We examined and compared autopsy brains from 4 groups (n = 15 each) of participants in the Baltimore Longitudinal Study of Aging: ASYMAD, mild cognitive impairment, AD, and age-matched controls. We found significant hypertrophy of the neuronal cell bodies, nuclei, and nucleoli of CA1 of hippocampus and anterior cingulate gyrus neurons in ASYMAD subjects compared with control and mild cognitive impairment cases. In the posterior cingulate gyrus and primary visual cortex, the hypertrophy was limited to the nuclei and nucleoli. The hypertrophy of cortical neurons and their nuclei and nucleoli in ASYMAD may represent an early reaction to the presence of neurotoxic A beta or tau, or a compensatory mechanism that prevents the progression of the disease into dementia. C1 [Iacono, Diego; Pletnikova, Olga; Rudow, Gay; Crain, Barbara; Troncoso, Juan C.] Johns Hopkins Univ, Div Neuropathol, Dept Pathol, Sch Med, Baltimore, MD 21205 USA. [O'Brien, Richard; Crain, Barbara; Troncoso, Juan C.] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21205 USA. [Resnick, Susan M.; Zonderman, Alan B.; An, Yang] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [West, Mark J.] Aarhus Univ, Inst Anat, Dept Neurobiol, DK-8000 Aarhus, Denmark. RP Troncoso, JC (reprint author), Johns Hopkins Univ, Div Neuropathol, Dept Pathol, Sch Med, Ross Bldg 558,720 Rutland Ave, Baltimore, MD 21205 USA. EM troncoso@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS [Z01 AG000191-11]; NIA NIH HHS [AG05146, K23 AG034550, P50 AG005146, P50 AG005146-25] NR 71 TC 71 Z9 71 U1 1 U2 6 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 JUN PY 2008 VL 67 IS 6 BP 578 EP 589 DI 10.1097/NEN.0b013e3181772794 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 310UR UT WOS:000256556500006 PM 18520776 ER PT J AU Croft, BY AF Croft, Barbara Y. TI NCI cancer imaging program update SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 NCI, Canc Imaging Program, Bethesda, MD 20892 USA. RP Croft, BY (reprint author), NCI, Canc Imaging Program, Bethesda, MD 20892 USA. RI Croft, Barbara/D-1248-2013 OI Croft, Barbara/0000-0003-2544-150X NR 0 TC 2 Z9 2 U1 0 U2 0 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 JUN PY 2008 VL 49 IS 6 BP 40N EP 42N PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 309WN UT WOS:000256491000010 PM 18511822 ER PT J AU Miller, RS Becker, KG Prabhu, V Cooke, DW AF Miller, Ryan S. Becker, Kevin G. Prabhu, Vinayakumar Cooke, David W. TI Adipocyte gene expression is altered in formerly obese mice and as a function of diet composition SO JOURNAL OF NUTRITION LA English DT Article ID VISCERAL ADIPOSE-TISSUE; WEIGHT-LOSS; FAT; MICROARRAY; INFLAMMATION; PREVALENCE; C57BL/6J; SUCROSE; GLUCOSE; ADULTS AB In the development of obesity, the source of excess energy may influence appetite and metabolism. To determine the effects of differences in diet composition in obesity, mice were fed either a high-carbohydrate diet (HC; 10% fat energy) or a high-fat energy-restricted diet (HFR; 60% fat energy) over 18 wk in weight-matched groups of mice. To identify obesity-associated genes with persistently altered expression following weight reduction, mice were fed either a standard low-fat diet (LF; 10% fat energy), an unrestricted high-fat diet (HF; 60% fat energy), or a HF diet followed by weight reduction OR). Mice fed a HF diet had significantly greater gonadal fat mass and higher whole blood glucose concentrations than mice fed an HC diet. Of the mice fed a high-fat diet, total body weight and serum insulin concentrations were greater in HF than in HFR. Microarray analysis revealed that HF vs. HC feeding resulted in global differences in adipocyte gene expression patterns. Although we identified genes whose expression was altered in both moderately and severely obese mice, there were also a large number of genes with altered expression only in severe obesity. Formerly obese, WR mice did not differ significantly from lean controls in total body weight or physiological measures. However, microarray analysis revealed distinctly different patterns of adipocyte gene expression. Furthermore, there were 398 genes with altered expression in HF mice that persisted in WR mice. Genes with persistently altered expression following obesity may play a role in rebound weight gain following weight reduction. C1 [Miller, Ryan S.; Cooke, David W.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. [Miller, Ryan S.; Cooke, David W.] Johns Hopkins Univ, Sch Med, Ilyssa Ctr Mol & Cellular Enocrinol, Baltimore, MD 21287 USA. [Becker, Kevin G.; Prabhu, Vinayakumar] NIA, Gene Express & Genom Unit, Baltimore, MD 21224 USA. RP Miller, RS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. EM rsmiller@jhmi.edu OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS; NIDDK NIH HHS [T32 DK007751, DK55831, R01 DK055831, R01 DK055831-05] NR 34 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUN PY 2008 VL 138 IS 6 BP 1033 EP 1038 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 301UK UT WOS:000255920900008 PM 18492830 ER PT J AU Kaefer, CM Milner, JA AF Kaefer, Christine M. Milner, John A. TI The role of herbs and spices in cancer prevention SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE diet; herbs; spices; cancer prevention ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; TOTAL ANTIOXIDANT CAPACITY; CROCUS-SATIVUS L.; INDUCIBLE CYCLOOXYGENASE; DIETARY ANTIOXIDANTS; MOLECULAR TARGETS; MOUSE MACROPHAGES; DOWN-REGULATION; GASTRIC-CANCER AB Historically, herbs and spices have enjoyed a rich tradition of use for their flavor enhancement characteristics and for their medicinal properties. The rising prevalence of chronic diseases worldwide and the corresponding rise in health care costs is propelling interest among researchers and the public for multiple health benefits related to these food items, including a reduction in cancer risk and modification of tumor behavior. A growing body of epidemiological and preclinical evidence points to culinary herbs and spices as minor dietary constituents with multiple anticancer characteristics. This review focuses on the antimicrobial, antioxidant, and antitumorigenic properties of herbs and spices; their ability to influence carcinogen bioactivation; and likely anticancer contributions. While culinary herbs and spices present intriguing possibilities for health promotion, more complete information is needed about the actual exposures to dietary components that are needed to bring about a response and the molecular target(s) for specific herbs and spices. Only after this information is obtained will it be possible to define appropriate intervention strategies to achieve maximum benefits from herbs and spices without eliciting ill consequences. Published by Elsevier Inc. C1 [Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. EM milnerj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 98 TC 140 Z9 145 U1 2 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUN PY 2008 VL 19 IS 6 BP 347 EP 361 DI 10.1016/j.jnutbio.2007.11.003 PG 15 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 310DS UT WOS:000256509700001 PM 18499033 ER PT J AU Jindal, V Ge, A Mansky, PJ AF Jindal, Vanita Ge, Adeline Mansky, Patrick J. TI Safety and efficacy of acupuncture in children - A review of the evidence SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Review DE acupuncture; pediatrics; review; side effects ID RANDOMIZED-CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; POSTOPERATIVE NAUSEA; LASER ACUPUNCTURE; ALLERGIC RHINITIS; CANCER-PATIENTS; BACK-PAIN; PROPHYLAXIS; ELECTROACUPUNCTURE; TONSILLECTOMY AB Acupuncture has been used therapeutically in China for thousands of years and is growing in prominence in Europe and the United States. In a recent review of complementary and alternative medicine use in the US population, an estimated 2.1 million people or 1.1% of the population sought acupuncture care during the past 12 months. Four percent of the US population used acupuncture at any time in their lives. We reviewed 31 different published journal articles, including 23 randomized controlled clinical trials and 8 meta-analysis/systematic reviews. We found evidence of some efficacy and low risk associated with acupuncture in pediatrics. From all the conditions we reviewed, the most extensive research has looked into acupuncture's role in managing postoperative and chemotherapy-induced nausea/vomiting. Postoperatively, there is far more evidence of acupuncture's efficacy for pediatrics than for children treated with chemotherapy. Acupuncture seems to be most effective in preventing postoperative induced nausea in children. For adults, research shows that acupuncture can inhibit chemotherapy-related acute vomiting, but conclusions about its effects in pediatrics cannot be made on the basis of the available published clinical trials data to date. Besides nausea and vomiting, research conducted in pain has yielded the most convincing results on acupuncture efficacy. Musculoskeletal and cancer-related pain commonly affects children and adults, but unfortunately, mostly adult studies have been conducted thus far. Because the manifestations of pain can be different in children than in adults, data cannot be extrapolated from adult research. Systematic reviews have shown that existing data often lack adequate control groups and sample sizes. Vas et at, Alimi et al, and Mehling et al demonstrated some relief for adults treated with acupuncture but we could not find any well-conducted randomized controlled studies that looked at pediatrics and acupuncture exclusively. Pain is often unresolved from drug therapy, thus there is a need for more studies in this setting. For seasonal allergic rhinitis, we reviewed studies conducted by Ng et al and Xue et al in children and adults, respectively. Both populations showed some relief of symptoms through acupuncture, but questions remain about treatment logistics. Additionally, there are limited indications that acupuncture may help cure children afflicted with nocturnal enuresis. Systematic reviews show that current published trials have suffered from low trial quality, including small sample sizes. Other areas of pediatric afflictions we reviewed that suffer from lack of research include asthma, other neurologic conditions, gastrointestinal disorders, and addiction. Acupuncture has become a dominant complementary and alternative modality in clinical practice today, but its associated risk has been questioned. The National Institutes of Health Consensus Statement states "one of the advantages of acupuncture is that the incidence of adverse effects is substantially lower than that of many drugs or other accepted procedures for the same conditions." A review of serious adverse events by White et al found the risk of a major complication occurring to have an incidence between 1:10,000 and 1:100,000, which is considered "very low." Another study found that the risk of a serious adverse event occurring from acupuncture therapy is the same as taking penicillin. The safety of acupuncture is a serious concern, particularly in pediatrics. Because acupuncture's mechanism is not known, the use of needles in childrn becomes questionable. For example, acupoints on the vertex of infants should not be needled when the fontanel is not closed. It is also advisable to apply few needles or delay treatment to the children who have overeaten, are overfatigued, or are very weak. Through our review of pediatric adverse events, we found a 1.55 risk of adverse events occurring in 100 treatments of acupuncture that coincides with the low risk detailed in the studies mentioned previously. The actual risk to an individual patient is hard to determine because certain patients, such as an immunosuppressed patient, can be predisposed to an increased risk, acupuncturist's qualifications differ, and practices vary in certain parts of the world. Nevertheless, it seems acupuncture is a safe complementary/alternative medicine modality for pediatric patients on the basis of the data we reviewed. C1 [Jindal, Vanita; Ge, Adeline; Mansky, Patrick J.] NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS,CRC, Bethesda, MD 20892 USA. RP Mansky, PJ (reprint author), NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS,CRC, 10 Ctr Dr,Room 4-1741,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov FU Intramural NIH HHS [Z99 AT999999, Z01 AT000004-06] NR 56 TC 56 Z9 58 U1 0 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUN PY 2008 VL 30 IS 6 BP 431 EP 442 DI 10.1097/MPH.0b013e318165b2cc PG 12 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 310NB UT WOS:000256535200004 PM 18525459 ER PT J AU Ambalavanan, N Van Meurs, KP Perritt, R Carlo, WA Ehrenkranz, RA Stevenson, DK Lemons, JA Poole, WK Higgins, RD AF Ambalavanan, N. Van Meurs, K. P. Perritt, R. Carlo, W. A. Ehrenkranz, R. A. Stevenson, D. K. Lemons, J. A. Poole, W. K. Higgins, R. D. CA NICHD Neonatal Res Network TI Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure SO JOURNAL OF PERINATOLOGY LA English DT Article DE logistic models; predictive value of tests; ROC curve ID INHALED NITRIC-OXIDE; MECHANICAL VENTILATION; PREMATURE-INFANTS; LUNG-DISEASE; CLASSIFICATION; NEWBORNS; TRIALS; RISK AB Objectives: To identify the variables that predict death/physiologic bronchopulmonary dysplasia (BPD) in preterm infants with severe respiratory failure. Study Design: The study was a secondary analysis of data from the NICHD Neonatal Research Network trial of inhaled nitric oxide (iNO) in preterm infants. Stepwise logistic regression models and Classification and Regression Tree (CART) models were developed for the outcome of death or physiologic BPD (O-2 at 36 weeks post-menstrual age). Result: Death and/or BPD was associated with lower birth weight, higher oxygen requirement, male gender, additional surfactant doses, higher oxygenation index and outborn status, but not the magnitude of response in PaO2 to iNO. The positive predictive value of the CART model was 82% at 95% sensitivity. Conclusions: The major factors associated with death/BPD were an increased severity of respiratory failure, lower birth weight, male gender and outborn status, but not the magnitude of initial response to iNO. C1 [Ambalavanan, N.; Carlo, W. A.] Univ Alabama, Dept Pediat, Birmingham, AL 35249 USA. [Van Meurs, K. P.; Stevenson, D. K.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Perritt, R.] RTI Int, Res Triangle Pk, NC USA. [Ehrenkranz, R. A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Lemons, J. A.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46204 USA. [Higgins, R. D.; NICHD Neonatal Res Network] NICHD Neonatal Res Network, Bethesda, MD USA. RP Ambalavanan, N (reprint author), Univ Alabama, Dept Pediat, 525 New Hillman Bldg,619 S 20th St, Birmingham, AL 35249 USA. EM ambal@uab.edu OI Steinhorn, Robin/0000-0002-0344-2328; Ambalavanan, Namasivayam/0000-0003-0731-9092 FU NCATS NIH HHS [UL1 TR000454]; NCRR NIH HHS [M01 RR000039, M01 RR000039-47, M01 RR000044, M01 RR000044-45, M01 RR000070, M01 RR000070-42, M01 RR00039, M01 RR00044, M01 RR00070, M01 RR000750, M01 RR000750-36, M01 RR006022, M01 RR006022-14, M01 RR00750, M01 RR008084, M01 RR008084-15, M01 RR06022, M01 RR08084]; NICHD NIH HHS [U10 HD027853, U01 HD036790, U01 HD036790-10, U01 HD040636, U10 HD021373, U10 HD021373-25, U10 HD021385, U10 HD021385-20, U10 HD027851, U10 HD027851-19, U10 HD027853-15, U10 HD027856, U10 HD027856-19, U10 HD027871, U10 HD027871-19, U10 HD027880, U10 HD027880-18, U10 HD027904, U10 HD027904-14, U10 HD034216, U10 HD034216-14, U10 HD040461, U10 HD040461-05, U10 HD040498, U10 HD040498-05, U10 HD040521, U10 HD040521-05, U10 HD040689, U10 HD040689-09, U10 HD21373, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40498, U10 HD40521, U10 HD40689] NR 20 TC 33 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD JUN PY 2008 VL 28 IS 6 BP 420 EP 426 DI 10.1038/jp.2008.18 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 309CF UT WOS:000256437600007 PM 18337740 ER PT J AU Deterding, LJ Bunger, MK Banks, GC Tomer, KB Archer, TK AF Deterding, Leesa J. Bunger, Maureen K. Banks, Geoffrey C. Tomer, Kenneth B. Archer, Trevor K. TI Global changes in and characterization of specific sites of phosphorylation in mouse and human histone H1 isoforms upon CDK inhibitor treatment using mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE H1 histories; chromatin; phosphorylation; mass spectrometry; CDK inhibitors; tandem mass spectrometry ID EXPRESSION IN-VIVO; DNA-REPLICATION; LINKER HISTONES; MMTV PROMOTER; CHROMATIN; TRANSCRIPTION; KINASE; RECEPTOR; CHROMOSOME; NUCLEOSOME AB Global changes in the phosphorylation state of human H1 isoforms isolated from UL3 cells have been investigated using mass spectrometry. Relative changes in H1 phosphorylation between untreated cells and cells treated with dexamethasone or various CDK inhibitors were determined. The specific cyclin-dependent kinase consensus sites of phosphorylation on the histone H1 isoforms that show changes in phosphorylation were also investigated. Three sites of phosphorylation on histone H1.4 isoforms have been identified. C1 [Deterding, Leesa J.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Bunger, Maureen K.; Banks, Geoffrey C.; Archer, Trevor K.] NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. EM deterdi2@niehs.nih.gov; archerl@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS [Z01 ES050171-08, Z01 ES071006-09, Z99 ES999999] NR 42 TC 17 Z9 18 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2008 VL 7 IS 6 BP 2368 EP 2379 DI 10.1021/pr700790a PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 311KL UT WOS:000256599000020 PM 18416567 ER PT J AU Mintz, M Vanderver, A Brown, KJ Lin, J Wang, Z Kaneski, C Schiffmann, R Nagaraju, K Hoffman, EP Hathout, Y AF Mintz, Michelle Vanderver, Adeline Brown, Kristy J. Lin, Joseph Wang, Zuyi Kaneski, Christine Schiffmann, Raphael Nagaraju, Kanneboyina Hoffman, Eric P. Hathout, Yetrib TI Time series proteome profiling to study endoplasmic reticulum stress response SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE SILAC; isotope ratio LC-MS/MS; proteome profiling; time series; ER stress; GRP78; reticulocalbin ID TANDEM MASS-SPECTROMETRY; CELL-CULTURE SILAC; MULTIPLE EF-HAND; AMINO-ACIDS; CA2+-BINDING PROTEIN; MUSCLE REGENERATION; SECRETORY PATHWAY; CREC FAMILY; QUANTITATION; EXPRESSION AB Time series profiling is a powerful approach for obtaining information on protein expression dynamics and prevailing biochemical pathways. To date, such information could only be obtained at the mRNA level using mature and highly parallel technologies such as microarray gene expression profiling. The generation of time series data at the protein level has lagged due to the lack of robust and highly reproducible methodologies. Using a combination of SILAC strategy, SDS-PAGE and LC-MS/MS, we demonstrate successful monitoring of expression levels of the same set of proteins across different time points within the ER compartment of human primary fibroblast cells when exposed to ER stress inducers tunicamycin and thapsigargin. Data visualization was facilitated using GeneSpring GX analysis platform that was designed to process Affymetrix microarray data. This software also facilitated the generation of important parameters such as data normalization, calculation of statistical values to extract significant changes in protein expression, and the cross comparison of data sets. C1 [Mintz, Michelle; Vanderver, Adeline; Brown, Kristy J.; Lin, Joseph; Wang, Zuyi; Nagaraju, Kanneboyina; Hoffman, Eric P.; Hathout, Yetrib] Childrens Natl Med Ctr, Ctr Med Genet, Washington, DC 20010 USA. [Kaneski, Christine; Schiffmann, Raphael] NINDS, NIH, Bethesda, MD 20892 USA. RP Hathout, Y (reprint author), Childrens Natl Med Ctr, Ctr Med Genet, Washington, DC 20010 USA. EM yhathout@cnmcresearch.org OI Brown, Kristy/0000-0002-1047-4328; Kaneski, Christine/0000-0003-1453-2502 FU Intramural NIH HHS; NICHD NIH HHS [T32 HD046388, 5R24 HD050846, K12HD001399, R24 HD050846, K12 HD001399, P30 HD040677, IDDRC 1P30HD40677, 5T32HD046388]; NINDS NIH HHS [K08 NS060695] NR 43 TC 22 Z9 22 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2008 VL 7 IS 6 BP 2435 EP 2444 DI 10.1021/pr700842m PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 311KL UT WOS:000256599000027 PM 18435558 ER PT J AU Low, NCP Cui, LH Merikangas, KR AF Low, Nancy C. P. Cui, Lihong Merikangas, Kathleen R. TI Specificity of familial transmission of anxiety and comorbid disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE familial aggregation/transmission; specificity of transmission; anxiety disorders; panic disorder; social anxiety/phobia; comorbidity ID NATIONAL EPIDEMIOLOGIC SURVEY; DIRECT-INTERVIEW FAMILY; ALCOHOL-USE DISORDERS; PANIC DISORDER; SOCIAL PHOBIA; HISTORY METHOD; PSYCHIATRIC-DISORDERS; SURVEY REPLICATION; MAJOR DEPRESSION; MENTAL-DISORDERS AB This study examines the specificity and impact of comorbid disorders in probands on the familial transmission of panic and social anxiety disorders. It employs a contemporary family study design with 225 probands (with and without panic and social anxiety disorders) sampled from outpatient clinics and the local community. Their 1053 adult first-degree relatives were assessed for lifetime disorders, based on best estimate diagnoses derived from semi-structured psychiatric diagnostic interviews (Schedule for Affective Disorders and Schizophrenia), multi-informant family history information, and medical records. Generalized estimating equations were used to examine the familial aggregation of panic and social anxiety disorders, and the contributions of comorbid disorders. Results show specificity of familial aggregation of both panic disorder and social anxiety in probands and relatives (i.e., panic odds ratio = 3.7, 95%CI 1.5-9.3; social anxiety odds ratio = 1.8, 95%CI 1.1-2.9) after controlling for comorbid disorders. There was no contribution of common comorbid disorders (depression, alcoholism, generalized anxiety disorder and agoraphobia) in probands on the familial aggregation of either disorder. These findings confirm prior studies of specificity of familial transmission of panic and social anxiety disorders, and demonstrate that the association between these disorders in probands is not attributable to comorbid mood, anxiety or substance use disorders. Therefore, despite the high magnitude of co-occurrence of panic disorder and social anxiety, there may be distinct etiologic factors underlying each disorder. These findings have implications for studies of the etiology, genetics, and treatment of these disorders. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Low, Nancy C. P.] McGill Univ, Dept Psychiat, Montreal, PQ H3A 1A1, Canada. [Low, Nancy C. P.; Cui, Lihong; Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Program,Dept Hlth & Huma, Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Low, NCP (reprint author), McGill Univ, Dept Psychiat, 1033 Pine Ave W,Room 104, Montreal, PQ H3A 1A1, Canada. EM Nancy.Low@mcgill.ca NR 51 TC 21 Z9 21 U1 6 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2008 VL 42 IS 7 BP 596 EP 604 DI 10.1016/j.jpsychires.2007.07.002 PG 9 WC Psychiatry SC Psychiatry GA 294RU UT WOS:000255424000011 PM 17706672 ER PT J AU Lockenhoff, CE Terracciano, A Bienvenu, OJ Patriciu, NS Nestadt, G McCrae, RR Eaton, WW Costa, PT AF Loeckenhoff, Corinna E. Terracciano, Antonio Bienvenu, O. Joseph Patriciu, Nicholas S. Nestadt, Gerald McCrae, Robert R. Eaton, William W. Costa, Paul T., Jr. TI Ethnicity, education, and the temporal stability of personality traits in the East Baltimore Epidemiologic Catchment Area study SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article DE personality; Five-Factor Model; temporal stability indices; demographics; ethnicity; education; age; Epidemiologic Catchment Area ID LIFE-COURSE; FOLLOW-UP; INTRAINDIVIDUAL CHANGE; MAJOR DEPRESSION; COMMUNITY SAMPLE; GENETIC-ANALYSIS; 5-FACTOR MODEL; 5 CULTURES; AGE; EXPERIENCES AB We examined the influence of age, gender, Black vs. White ethnicity, and education on five indices of personality stability and change across an average interval of 8 years in the East Baltimore Epidemiologic Catchment Area study. In the full sample (n = 505, aged 30-88), examination of structural, rank-order, ipsative, and mean level stability, as well as indices of reliable change suggested that NEO-PI-R personality traits showed moderate to high levels of stability over time. There were few age and gender effects on temporal stability but rank-order, ipsative, and mean level stability were lower among Blacks and individuals with lower education. Future research should explore additional demographic predictors of temporal plasticity in a diverse range of samples, and employ observer ratings to assess personality. Published by Elsevier Inc. C1 [Loeckenhoff, Corinna E.; Terracciano, Antonio; Patriciu, Nicholas S.; McCrae, Robert R.; Costa, Paul T., Jr.] NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH,DHHS, Baltimore, MD 21224 USA. [Bienvenu, O. Joseph; Nestadt, Gerald; Costa, Paul T., Jr.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. [Eaton, William W.; Costa, Paul T., Jr.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21218 USA. RP Lockenhoff, CE (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH,DHHS, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LoeckenhoffC@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; OI Loeckenhoff, Corinna/0000-0003-1605-1323; Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [ZIA AG000183-22, NIH0011894836, Z01 AG000183-19, Z99 AG999999, ZIA AG000183-23]; NIMH NIH HHS [K23 MH064543, K23 MH064543-05, R01 MH047447, R01 MH047447-15, R01 MH050616, R01 MH050616-09] NR 65 TC 40 Z9 40 U1 5 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD JUN PY 2008 VL 42 IS 3 BP 577 EP 598 DI 10.1016/j.jrp.2007.09.004 PG 22 WC Psychology, Social SC Psychology GA 317AD UT WOS:000256990600005 PM 19122849 ER PT J AU Issaq, HJ Abbott, E Veenstra, TD AF Issaq, Haleem J. Abbott, Eric Veenstra, Timothy D. TI Utility of separation science in metabolomic studies SO JOURNAL OF SEPARATION SCIENCE LA English DT Review DE chromatography; disease biomarkers; metabolomics; metabonomics; metabolites ID SUPERCRITICAL-FLUID CHROMATOGRAPHY; ELECTROPHORESIS-MASS-SPECTROMETRY; PRESSURE LIQUID-CHROMATOGRAPHY; CAPILLARY-ELECTROPHORESIS; HUMAN URINE; GAS-CHROMATOGRAPHY; ENDOGENOUS ESTROGENS; PLANT METABOLOMICS; HUMAN SERUM; METABOLITES AB Metabolomics, or alternately metabonomics, an emerging field of biochemical research, is a complementary technique to genomics, transcriptomics, and proteomics. Direct quantitative measurements of metabolite expressions in urine, serum, plasma, and tissue are essential for the study of biological processes in normal and disease states. Since the number of metabolites in a biological sample is large separation science plays an important role in metabolomic research. This review describes the role of GC, HPLC, CE, and supercritical fluid chromatography in metabolomic research. The application of each technique is discussed and its advantages and limitations are discussed with selective illustrative examples. C1 [Issaq, Haleem J.; Abbott, Eric; Veenstra, Timothy D.] SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, NCI Frederick, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, NCI Frederick, 1050 Boyles St,POB B, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 62 TC 36 Z9 40 U1 0 U2 21 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1615-9306 EI 1615-9314 J9 J SEP SCI JI J. Sep. Sci. PD JUN PY 2008 VL 31 IS 11 BP 1936 EP 1947 DI 10.1002/jssc.200700601 PG 12 WC Chemistry, Analytical SC Chemistry GA 323SD UT WOS:000257467800006 PM 18348322 ER PT J AU Bartesaghi, A Sprechmann, P Liu, J Randall, G Sapiro, G Subramaniam, S AF Bartesaghi, A. Sprechmann, P. Liu, J. Randall, G. Sapiro, G. Subramaniam, S. TI Classification and 3D averaging with missing wedge correction in biological electron tomography SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE cryo-electron tomography; missing wedge effect; volume registration; volume classification; volume averaging ID CRYOELECTRON TOMOGRAPHY; MACROMOLECULES; REFINEMENT; RESOLUTION; IMAGES; VIEWS; CELLS; ICE AB Strategies for the determination of 3D structures of biological macromolecules using electron crystallography and single-particle electron microscopy utilize powerful tools for the averaging of information obtained from 2D projection images of structurally homogeneous specimens. In contrast, electron tomographic approaches have often been used to study the 3D structures of heterogeneous, one-of-a-kind objects such as whole cells where image-averaging strategies are not applicable. Complex entities such as cells and viruses, nevertheless, contain multiple copies of numerous macromolecules that can individually be subjected to 3D averaging. Here we present a complete framework for alignment, classification, and averaging of volumes derived by electron tomography that is computationally efficient and effectively accounts for the missing wedge that is inherent to limited-angle electron tomography. Modeling the missing data as a multiplying mask in reciprocal space we show that the effect of the missing wedge can be accounted for seamlessly in all alignment and classification operations. We solve the alignment problem using the convolution theorem in harmonic analysis, thus eliminating the need for approaches that require exhaustive angular search, and adopt an iterative approach to alignment and classification that does not require the use of external references. We demonstrate that our method can be successfully applied for 3D classification and averaging of phantom volumes as well as experimentally obtained tomograms of GroEL where the outcomes of the analysis can be quantitatively compared against the expected results. (c) 2008 Elsevier Inc. All rights reserved. C1 [Bartesaghi, A.; Liu, J.; Subramaniam, S.] Natl Inst Hlth, Ctr Canc Res, Bethesda, MD 20892 USA. [Sprechmann, P.; Randall, G.] Univ Republica, Inst Ingn Elect, Montevideo 11800, Uruguay. [Sapiro, G.] Univ Minnesota, Minneapolis, MN 55455 USA. RP Subramaniam, S (reprint author), Natl Inst Hlth, Ctr Canc Res, Bldg 50,Room 4306, Bethesda, MD 20892 USA. EM ss1@nih.gov FU Intramural NIH HHS [Z01 BC010278-10, Z99 CA999999] NR 27 TC 76 Z9 77 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUN PY 2008 VL 162 IS 3 BP 436 EP 450 DI 10.1016/j.jsb.2008.02.008 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 312QB UT WOS:000256684800009 PM 18440828 ER PT J AU Nagao, E Arie, T Dorward, DW Fairhurst, RM Dvorak, JA AF Nagao, Eriko Arie, Takayuki Dorward, David W. Fairhurst, Rick M. Dvorak, James A. TI The avian malaria parasite Plasmodium gallinaceum causes marked structural changes on the surface of its host erythrocyte SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Plasmodium gallinaceum; avian malaria; erythrocyte; surface topography; atomic force microscopy ID FALCIPARUM-INFECTED ERYTHROCYTES; ATOMIC-FORCE MICROSCOPY; HUMAN CEREBRAL MALARIA; FINE-STRUCTURE; TRAFFICKING; ULTRASTRUCTURE; MEMBRANE; CELLS; SEQUESTRATION; CYTOADHERENCE AB Using a combination of atomic force, scanning and transmission electron microscopy, we found that avian erythrocytes infected with the avian malaria parasite Plasmodium gallinaceum develop similar to 60 nm wide and similar to 430 nm long furrow-like structures on the surface. Furrows begin to appear during the early trophozoite stage of the parasite's development. They remain constant in size and density during the course of parasite maturation and are uniformly distributed in random orientations over the erythrocyte surface. In addition, the density of furrows is directly proportional to the number of parasites contained within the erythrocyte. These findings suggest that parasite-induced intraerythrocytic processes are involved in modifying the surface of host erythrocytes. These processes may be analogous to those of the human malaria parasite A falciparum, which induces knob-like protrusions that mediate the pathogenic adherence of parasitized erythrocytes to microvessels. Although P. gallinaceum-infected erythrocytes do not seem to adhere to microvessels in the host chicken, the furrows might be involved in the pathogenesis of P. gallinaceum infections by some other mechanism involving host-pathogen interactions. Published by Elsevier Inc. C1 [Nagao, Eriko; Arie, Takayuki; Fairhurst, Rick M.; Dvorak, James A.] NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Dorward, David W.] NIAID, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Arie, T (reprint author), NIAID, NIH, Lab Malaria & Vector Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM TArie@niaid.nih.gov FU Intramural NIH HHS [NIH0010970596, Z01 AI001000-01] NR 40 TC 10 Z9 10 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUN PY 2008 VL 162 IS 3 BP 460 EP 467 DI 10.1016/j.jsb.2008.03.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 312QB UT WOS:000256684800011 PM 18442920 ER PT J AU Ralston, E Swaim, B Czapiga, M Hwu, WL Chien, YH Pittis, MG Bembi, B Schwartz, O Plotz, P Raben, N AF Ralston, E. Swaim, B. Czapiga, M. Hwu, W-L. Chien, Y. -H. Pittis, M. G. Bembi, B. Schwartz, O. Plotz, P. Raben, N. TI Detection and imaging of non-contractile inclusions and sarcomeric anomalies in skeletal muscle by second harmonic generation combined with two-photon excited fluorescence SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE muscle; Pompe disease; autophagy; acid alpha-glucosidase; two-photon microscopy; second harmonic generation; two-photon excited fluorescence ID IN-VIVO; STORAGE-DISEASE; MICROSCOPY; FIBERS; MYOPATHIES; LASER; ACCUMULATION; LIPOFUSCIN; CELLS AB The large size of the multinucleated muscle fibers of skeletal muscle makes their examination for structural and pathological defects a challenge. Sections and single fibers are accessible to antibodies and other markers but imaging of such samples does not provide a three-dimensional view of the muscle. Regrettably, bundles of fibers cannot be stained or imaged easily. Two-photon microscopy techniques overcome these obstacles. Second harmonic generation (SHG) by myosin filaments and two-photon excited fluorescence (2PEF) of mitochondrial and lysosomal components provides detailed structural information on unstained tissue. Furthermore, the infrared exciting light can penetrate several layers of muscle fibers and the minimal processing is particularly valuable for fragile biopsies. Here we demonstrate the usefulness of SHG, combined with 2PEF, to reveal enlarged lysosomes and accumulations of non-contractile material in muscles from the mouse model for the lysosomal storage disorder Pompe disease (PD), and in biopsies from adult and infant PD patients. SHG and 2PEF also detect sarcomeric defects that may presage the loss of myofibrils in atrophying muscle and signify loss of elasticity. The combination of SHG and 2PEF should be useful in the analysis and diagnosis of a wide range of skeletal muscle pathologies. Published by Elsevier Inc. C1 [Ralston, E.] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. [Swaim, B.] Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Czapiga, M.; Schwartz, O.] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Hwu, W-L.; Chien, Y. -H.] Natl Taiwan Univ Hosp, Dept Pediat & Med Genet, Taipei, Taiwan. [Pittis, M. G.; Bembi, B.] Pediat Hosp Burlo Garofalo, Trieste, Italy. [Plotz, P.; Raben, N.] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Ralston, E (reprint author), NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bldg 50,Room 1535, Bethesda, MD 20892 USA. EM ralstone@mail.nih.gov OI HWU, WUH-LIANG/0000-0001-6690-4879; CHIEN, YIN-HSIU/0000-0001-8802-5728 FU Intramural NIH HHS [Z01 AR041132-06, Z99 AR999999] NR 36 TC 32 Z9 32 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUN PY 2008 VL 162 IS 3 BP 500 EP 508 DI 10.1016/j.jsb.2008.03.010 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 312QB UT WOS:000256684800015 PM 18468456 ER PT J AU Pine, DS Guyer, AE Goldwin, M Towbin, KA Leibenluft, E AF Pine, Daniel S. Guyer, Amanda E. Goldwin, Michelle Towbin, Kenneth A. Leibenluft, Ellen TI Autism spectrum disorder scale scores in pediatric mood and anxiety disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE mood disorder; anxiety disorder; autism spectrum; impairment ID PERVASIVE DEVELOPMENTAL DISORDERS; BIPOLAR DISORDER; DIAGNOSTIC INTERVIEW; LANGUAGE IMPAIRMENT; BROAD AUTISM; CHILDREN; TRAITS; FLEXIBILITY; ADOLESCENTS; POPULATION AB Objective: To compare scores on autism spectrum disorder (ASD) symptom scales in healthy youths and youths with mood or anxiety disorders. Method: A total of 352 youths were recruited (107 healthy participants, 88 with an anxiety disorder, 32 with major depressive disorder, 62 with bipolar disorder, and 63 with a mood disorder characterized by severe nonepisodic irritability). Participants received structured psychiatric interviews and parent ratings on at least one of three ASD symptom scales: Children's Communication Checklist, Social Communication Questionnaire, and Social Responsiveness Scale. Results: Relative to healthy youths, youths with mood or anxiety disorders exhibited higher scores on each ASD symptom scale. ASD symptom scale scores also showed an association with impairment severity and attention-cleficit/hyperactivity disorder. Among patients with mood disorders but not those with anxiety disorders, consistent, statistically significant associations between diagnosis and ASD symptom scale scores remained even after controlling for potential confounders. Conclusions: Patients with mood disorders exhibit higher scores on ASD symptom scales than healthy youths or youths with anxiety disorders. These data should alert clinicians to the importance of assessing ASD symptoms to identify social reciprocity and communication deficits as possible treatment targets in pediatric mood and anxiety disorders. C1 [Pine, Daniel S.; Guyer, Amanda E.; Goldwin, Michelle; Towbin, Kenneth A.] NIMH, Sect Dev & Affect Neurosci, Emot & Dev Branch, MAP,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, MAP,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Sect Dev & Affect Neurosci, Emot & Dev Branch, MAP,NIH,Dept Hlth & Human Serv, 15K North Dr, Bethesda, MD 20892 USA. EM pined@mail.nih.gov FU Intramural NIH HHS [Z01 MH002781-06, Z01 MH002786-06, Z01 MH002778-08] NR 35 TC 56 Z9 57 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2008 VL 47 IS 6 BP 652 EP 661 DI 10.1097/CHI.0b013e31816bffa5 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 304LM UT WOS:000256111000008 PM 18434923 ER PT J AU Crane, NJ McHone, B Hawksworth, J Pearl, JP Denobile, J Tadaki, D Pinto, PA Levin, IW Elster, EA AF Crane, Nicole J. McHone, Ben Hawksworth, Jason Pearl, Jonathan P. Denobile, John Tadaki, Doug Pinto, Peter A. Levin, Ira W. Elster, Eric A. TI Enhanced surgical imaging: Laparoscopic vessel identification and assessment of tissue oxygenation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LIVE-DONOR NEPHRECTOMY; MULTIPLE RENAL-ARTERIES; REFLECTANCE SPECTROSCOPY; CORONARY-ANGIOGRAPHY; COLONIC PERFUSION; PATENCY CONTROL; PULSE OXIMETRY; GRAFT PATENCY; FREE FLAPS; SURGERY AB BACKGROUND: Inherent to minimally invasive procedures are loss of tactile feedback and loss of three-dimensional assessment. Tasks such as vessel identification and dissection are not trivial for the inexperienced laparoscopic surgeon. Advanced surgical imaging, such as 3-charge-coupled device (3-CCD) image enhancement, can be used to assist with these more challenging tasks and, in addition, offers a method to noninvasively monitor tissue oxygenation during operations. STUDY DESIGN: In this study, 3-CCD image enhancement is used for identification of vessels in 25 laparoscopic donor and partial nephrectomy patients. The algorithm is then applied to two laparoscopic nephrectomy patients involving multiple renal arteries. We also use the 3-CCD camera to qualitatively monitor renal parenchymal oxygenation during 10 laparoscopic donor nephrectomies (LDNs). RESULTS: The mean region of interest (ROI) intensity Values obtained for the renal artery and vein (68.40 +/- 8.44 and 45.96 +/- 8.65, respectively) are used to calculate a threshold intensity value (59.00) that allows for objective vessel differentiation. In addition, we examined the renal parenchyma during LDNs. Mean ROI intensity values were calculated for the renal parenchyma at two distinct time points: before vessel stapling (nonischemic) and just before extraction from the abdomen (ischemic). The nonischemic mean ROI intensity values are statistically different from the ischemic mean ROI intensity values (p < 0.05), even with short ischemia times. CONCLUSIONS: We have developed a technique, 3-CCD image enhancement, for identification of vasculature and monitoring of parenchymal oxygenation. This technique requires no additional laparoscopic operating room equipment and has real-time video capability. C1 USN, Med Res Ctr, Silver Spring, MD 20910 USA. George Washington Univ, Dept Urol, Washington, DC USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA. Univ Hlth Sci, Uniformed Serv Univ, Dept Surg, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Crane, NJ (reprint author), USN, Med Res Ctr, 503 Grant Ave, Silver Spring, MD 20910 USA. EM eric.elster@nied.navy.mil FU Intramural NIH HHS [Z01 SC006659-25] NR 38 TC 11 Z9 12 U1 0 U2 3 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 JUN PY 2008 VL 206 IS 6 BP 1159 EP 1166 DI 10.1016/j.jamcollsurg.2008.01.013 PG 8 WC Surgery SC Surgery GA 310EO UT WOS:000256511900010 PM 18501814 ER PT J AU Hanna, BV Gorbach, AM Gage, FA Silva, JS Gilfillan, LG Elster, EA Kirk, AD AF Hanna, Barbara V. Gorbach, Alexander M. Gage, Frederic A. Silva, John S. Gilfillan, Lynne G. Elster, Eric A. Kirk, Allan D. TI Intraoperative assessment of critical biliary structures with visible range/infrared image fusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID BILE-DUCT INJURIES; CHOLECYSTECTOMY; PREVENTION C1 USN, Naval Med Res Ctr, Silver Spring, MD 20910 USA. Sarnoff Corp, Vis Technol Lab, Princeton, NJ USA. Natl Inst Biomed Imaging & Bioengn, Dept Bioengn & Phys Sci, NIH, Bethesda, MD USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD USA. Silva Consulting Serv, Eldersburg, MD USA. Sarnoff Corp, Bioresttex Div, Arlington, VA USA. Emory Univ Hosp, Emory Transplant Ctr, Atlanta, GA 30322 USA. Natl Naval Med Ctr, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD USA. RP Elster, EA (reprint author), USN, Naval Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 18 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2008 VL 206 IS 6 BP 1227 EP 1231 DI 10.1016/j.jamcollsurg.2007.10.012 PG 5 WC Surgery SC Surgery GA 310EO UT WOS:000256511900020 PM 18501824 ER PT J AU Fitzgerald, N Damio, G Segura-Perez, S Perez-Escamilla, R AF Fitzgerald, Nurguel Damio, Grace Segura-Perez, Sofia Perez-Escamilla, Rafael TI Nutrition knowledge, food label use, and food intake patterns among Latinas with and without type 2 diabetes SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID BREAST-FEEDING INITIATION; 3RD NATIONAL-HEALTH; PUERTO-RICAN WOMEN; DIETARY-INTAKE; CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; SWEETENED BEVERAGES; RISK-FACTORS; LIFE-STYLE; LOW-INCOME AB Objective To examine the associations of nutrition knowledge, food label use, and food intake patterns among Latinas with and without diagnosed diabetes. Design This was a case-control study. Subjects/setting A convenience sample of 201 (100 cases with diagnosed type 2 diabetes, 101 controls without diagnosed diabetes) nonpregnant, nonbreastfeeding Latinas without severe health conditions, aged 35 to 60 years were interviewed by bicultural interviewers. Diverse community-based recruitment methods were used. Statistical analyses performed Independent samples t test, Mann-Whitney U, and chi(2) tests, and multivariate logistic regression were performed. Results Food labels self-efficacy and stage of change, and average nutrition knowledge scores were similar between cases and controls (P>0.05). Within the diabetes group, nutrition knowledge was greater among those who had seen a registered dietitian or a diabetes educator (P=0.020). Cases reported consuming artificially sweetened desserts and beverages more frequently than controls (P<0.001). Pooled sample cross-sectional analyses showed that nutrition knowledge was positively related to food label use, which in turn was related to a more healthful food intake pattern (P<0.05). After adjusting for likely confounders, socioeconomic status (SES) was positively related to nutrition knowledge (P=0.001) and intakes of fruits, vegetables, and meats (P <= 0.01). SES was not related to food label use independently of nutrition knowledge. Acculturation was positively related to soft drink and salty snack intakes (P<0.01). Conclusions There is a need to improve nutrition knowledge and skills for both groups, especially for those with low SES. Culturally appropriate interventions should emphasize the healthful nutritional behaviors from one's primary culture for effective retention of such traits. C1 [Fitzgerald, Nurguel] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08901 USA. Rutgers State Univ, Family & Community Hlth Sci Dept, New Brunswick, NJ 08901 USA. [Perez-Escamilla, Rafael] Univ Connecticut, Dept Nutr Sci, Latino Hlth Dispar NIH EXPORT Ctr, Storrs, CT USA. [Damio, Grace; Segura-Perez, Sofia] Hispan Hlth Council, Ctr Community Nutr, Hartford, CT USA. [Damio, Grace] Hispan Hlth Council, Ctr Women & Childrens Hlth, Hartford, CT USA. RP Fitzgerald, N (reprint author), Rutgers State Univ, Family & Community Hlth Sci Dept, 26 Nichol Ave, New Brunswick, NJ 08901 USA. EM nfitzgerald@rce.rutgers.edu FU NIMHD NIH HHS [1P20MD001765-01] NR 49 TC 58 Z9 58 U1 4 U2 14 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 2008 VL 108 IS 6 BP 960 EP 967 DI 10.1016/j.jada.2008.03.016 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 309IL UT WOS:000256453800014 PM 18502226 ER PT J AU Menke, J Zeller, GC Kikawada, E Means, TK Huang, XR Lan, HY Lu, B Farber, J Luster, AD Kelley, VR AF Menke, Julia Zeller, Geraldine C. Kikawada, Eriya Means, Terry K. Huang, Xiao R. Lan, Han Y. Lu, Bao Farber, Joshua Luster, Andrew D. Kelley, Vicki R. TI CXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR CXCR3; MRL-FAS(LPR) MICE; AUTOIMMUNE-DISEASE; T-CELL; NEPHROTOXIC NEPHRITIS; ALLOGRAFT-REJECTION; GLOMERULAR INJURY; INDUCIBLE PROTEIN; RENAL-DISEASE AB Chemokines are instrumental in macrophage- and T cell-dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL-Fas(lpr) mice and the nephrotoxic serum nephritis model), but evidence suggests that multiple chemokines are involved. For identification of additional therapeutic targets for immune-mediated nephritis, chemokine ligands and receptors in CCL2(-/-) and wild-type (WT) MRL-Fas(lpr) kidneys were profiled. The focus was on intrarenal chemokine ligand/receptor pairs that were highly upregulated downstream of CCL2; the chemokine CXCL10 and its cognate receptor, CXCR3, stood out as potential therapeutic targets. However, renal disease was not suppressed in CXCL10(-/-) MRL-Fas(lpr) mice, and CXCL10(-/-) C57BL/6 mice were not protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3 engages with the ligand CXCL9, CXCR3(-/-), CXCL9(-/-), and CXCL10(-/-) B6 mice were compared with WT mice with nephrotoxic serum nephritis. Kidney disease, measured by loss of renal function and histopathology, was suppressed in both CXCR3(-/-) and CXCL9(-/-) mice but not in CXCL10(-/-) mice. With nephrotoxic serum nephritis, CXCR3(-/-) and CXCL9(-/-) mice had fewer intrarenal activated T cells and activated macrophages. Both IgG glomerular deposits and antigen-specific IgG in serum were reduced in these mice, suggesting that although CXCR3 and CXCL9 initiate nephritis through cell-mediated events, renal inflammation may be sustained by their regulation of IgG. It is concluded that specific blockade of CXCL9 or CXCR3 may be a potential therapeutic target for human immune-mediated kidney diseases. C1 [Menke, Julia; Zeller, Geraldine C.; Kikawada, Eriya; Kelley, Vicki R.] Brigham & Womens Hosp, Div Renal, Lab Mol Autoimmune Dis, Boston, MA 02115 USA. [Means, Terry K.; Luster, Andrew D.] Harvard Univ, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. [Lu, Bao] Harvard Univ, Childrens Hosp, Sch Med, Perlmutter Lab, Boston, MA 02115 USA. [Huang, Xiao R.; Lan, Han Y.] Univ Hong Kong, Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Farber, Joshua] NICHHD, Informat Biol Sect, Lab Mol Immunol, NIAID,NIH, Bethesda, MD 20892 USA. RP Kelley, VR (reprint author), Harvard Univ, Inst Med, 4 Blackfan Circle, Boston, MA 02115 USA. EM vkelley@rics.bwh.harvard.edu RI Lan, hui/C-9734-2015 OI Lan, hui/0000-0003-4283-9755 FU NCI NIH HHS [R01 CA 069212, R01 CA069212]; NIAMS NIH HHS [K01 AR051367, KO1 AR 051367]; NIDDK NIH HHS [DK 36149, DK 52369, DK 56848, R01 DK036149, R01 DK052369, R01 DK056848, Z01 DK036149] NR 54 TC 44 Z9 44 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2008 VL 19 IS 6 BP 1177 EP 1189 DI 10.1681/ASN.2007111179 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 307MK UT WOS:000256322800019 PM 18337479 ER PT J AU Dunson, DB Herring, AH Engel, SM AF Dunson, David B. Herring, Amy H. Engel, Stephanie M. TI Bayesian selection and clustering of polymorphisms in functionally related genes SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Bayesian; clustering; Dirichlet process; genetic association; hierarchical regression; multiple testing; nonparametric Bayes; single nucleotide polymorphisms; sparse regression ID CYTOKINE POLYMORPHISMS; NONPARAMETRIC PROBLEMS; MULTIPLE COMPARISONS; DIRICHLET PROCESSES; VARIABLE SELECTION; MICROARRAY DATA; REGRESSION; INFERENCE; MODELS; PROBABILITY AB In epidemiologic studies, there is often interest in assessing the relationship between polymorphisms in functionally related genes and a health outcome. For each candidate gene, single nucleotide polymorphism (SNP) data are collected at a number of locations, resulting in a large number of possible genotypes. Because instabilities can result in analyses that include all the SNPs, dimensionality is typically reduced by conducting single SNP analyses or attempting to identify haplotypes. This article proposes an alternative Bayesian approach for reducing dimensionality. A multilevel Dirichlet process prior is used for the distribution of the SNP-specific regression coefficients within genes, incorporating a variable selection-type mixture structure to allow SNPs with no effect. This structure allows simultaneous selection of important SNPs and soft clustering of SNPs having similar impact on the health outcome. The methods are illustrated using data from a study of pro- and anti-inflammatory cytokine polymorphisms and spontaneous preterm birth. C1 [Dunson, David B.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Herring, Amy H.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Engel, Stephanie M.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. RP Dunson, DB (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 41 TC 21 Z9 21 U1 2 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2008 VL 103 IS 482 BP 534 EP 546 DI 10.1198/016214507000000554 PG 13 WC Statistics & Probability SC Mathematics GA 329VA UT WOS:000257897500012 ER PT J AU Qin, J Shao, J Zhang, B AF Qin, Jing Shao, Jun Zhang, Biao TI Efficient and doubly robust imputation for covariate-dependent missing responses SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE covariate-dependent missing mechanism; doubly robust; imputation; local efficiency; model-assisted ID RATIO CONFIDENCE-INTERVALS; EMPIRICAL LIKELIHOOD; AUXILIARY INFORMATION; MULTIPLE IMPUTATION; TRAINING-PROGRAMS; COMPLEX SURVEYS; QUANTILES; MODEL AB In this article we study a well-known response missing-data problem. Missing data is an ubiquitous problem in medical and social science studies. Imputation is one of the most popular methods for dealing with missing data. The most commonly used imputation that makes use of covariates is regression imputation, in which the regression model can be parametric, semiparametric, or nonparametric. Parametric regression imputation is efficient but is not robust against misspecification of the regression model. Although nonparametric regression imputation (such as nearest-neighbor imputation and kernel regression imputation) is model-free, it is not efficient, especially if the dimension of covariate vector is high (the well-known problem of curse of dimensionality). Semiparametric regression imputation (such as partially linear regression imputation) can reduce the dimension of the covariate in nonparametric regression fitting but is not robust against misspecification of the linear component in the regression. Assuming that the missing mechanism is covariate-dependent and that the propensity function can be specified correctly, we propose a regression imputation method that has good efficiency and is robust against regression model misspecification. Furthermore, our method is valid as long as either the regression model or the propensity model is correct, a property known as the double-robustness property. We show that asymptotically the sample mean based on our imputation achieves the semiparametric efficient lower bound if both regression and propensity models are specified correctly. Our simulation results demonstrate that the proposed method outperforms many existing methods for handling missing data, especially when the regression model is misspecified. As an illustration, an economic observational data set is analyzed. C1 [Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Shao, Jun] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. [Zhang, Biao] Univ Toledo, Dept Math, Toledo, OH 43606 USA. RP Qin, J (reprint author), NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 19 Z9 21 U1 1 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2008 VL 103 IS 482 BP 797 EP 810 DI 10.1198/016214508000000238 PG 14 WC Statistics & Probability SC Mathematics GA 329VA UT WOS:000257897500037 ER PT J AU Laiyemo, AO Smoot, DT AF Laiyemo, Adeyinka O. Smoot, Duane T. TI Metastatic gastric stump cancer occurring six years after a partial gastrectomy for gastric ulcer SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE gastric; cancer; ulcer ID HELICOBACTER-PYLORI INFECTION; CARCINOMA; REMNANT AB This case was presented as an abstract at the American College of Gastroenterology 70th annual scientific meeting in Hawaii (October 28-November 2, 2005). Gastric stump cancer (GSC) is known to occur following partial gastrectomy for benign diseases. The risk is believed to increase four-to-five-fold 20 years after gastrectomy. We report a 41-year-old man with metastatic adenocarcinoma of the gastric stump six years after he underwent a partial gastrectomy for a gastric ulcer, following a major rebleeding episode. We highlight the need for identification of patients at risk of developing gastric stump cancer-especially as it has now been described in patients who underwent gastric bypass surgery for obesity-a population that continues to increase. C1 [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Biometry Res Grp,Div Canc Prevent,NIH, Bethesda, MD 20892 USA. [Smoot, Duane T.] Howard Univ Hosp, Dept Med, Div Gastroenterol, Washington, DC USA. RP Laiyemo, AO (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Biometry Res Grp,Div Canc Prevent,NIH, 6130 Execut Blvd,Suite 3121, Bethesda, MD 20892 USA. EM laiyemoa@mail.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUN PY 2008 VL 100 IS 6 BP 737 EP 739 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 313WR UT WOS:000256771200013 PM 18595579 ER PT J AU Lynch, TJ Blumenschein, GR Engelman, JA Espinoza-Delgado, I Govindan, R Hanke, J Hanna, NH Heymach, JV Hirsch, FR Janne, PA Lilenbaum, RC Natale, RB Riely, GJ Sequist, LV Shapiro, GT Shaw, A Shepherd, FA Socinski, M Sorensen, AG Wakelee, HA Weitzman, A AF Lynch, Thomas J., Jr. Blumenschein, George R., Jr. Engelman, Jeffrey A. Espinoza-Delgado, Igor Govindan, Ramaswamy Hanke, Jeff Hanna, Nasser H. Heymach, John V. Hirsch, Fred R. Janne, Pasi A. Lilenbaum, Rogerio C. Natale, Ronald B. Riely, Gregory J. Sequist, Lecia V. Shapiro, Geoffrey T. Shaw, Alice Shepherd, Frances A. Socinski, Mark Sorensen, A. Gregory Wakelee, Heather A. Weitzman, Aaron TI Summary statement - Novel Agents in the Treatment of Lung Cancer: Fifth Cambridge Conference assessing opportunities for combination therapy SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE lung cancer; profiling; biopsies; EGFR; VEGF; novel targets AB The promise of effective targeted therapy for lung cancer requires rigorous identification of potential targets combined with intensive discovery and development efforts aimed at developing effective "drugs" for these targets. We now recognize that getting the right drug to the right target in the right patient is more complicated than one could have imagined a decade ago. As knowledge of targets and development of agents have proliferated and advanced, so too have data demonstrating the biologic heterogeneity of tumors. The finding that lung cancers are genetically diverse and can exhibit several pathways of resistance in response to targeted agents makes the prospect for curative therapy more daunting. It is becoming increasingly clear that single-agent treatment will be the exception rather than the rule. This information raises important new questions about the development and assessment of novel agents in lung cancer treatment: (1) How do we identify the most important drug targets for tumor initiation and maintenance? (2) What is the best way to assess drug candidates that may only be relevant in a small fraction of patients? (3) What models do we use to predict clinical response and identify effective combinations? And (4) how do we bring combination regimens to the clinic, particularly when the agents are not yet approved individually and may be under development from different companies? The Fifth Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was held in Cambridge, Massachusetts, on October 1-2, 2007, to discuss these questions by reviewing recent progress in the field and advancing recommendations for research and patient care. New information, conclusions, and recommendations considered significant for the field by the program faculty are summarized here and presented at greater length in the individual articles and accompanying discussions that comprise the full conference proceedings. A CME activity based on this summary is also available at www.informedicalcme.com/cme. C1 [Lynch, Thomas J., Jr.; Engelman, Jeffrey A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Blumenschein, George R., Jr.; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Espinoza-Delgado, Igor] NCI, Bethesda, MD 20892 USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO USA. [Hanke, Jeff] AstraZeneca, Waltham, MA USA. [Hanna, Nasser H.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Hirsch, Fred R.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Janne, Pasi A.; Shapiro, Geoffrey T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lilenbaum, Rogerio C.] Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. [Natale, Ronald B.] Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shaw, Alice] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Shepherd, Frances A.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Socinski, Mark] Univ N Carolina, Chapel Hill, NC USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, MGH HST AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wakelee, Heather A.] Stanford Univ, Ctr Canc, Stanford, CA 94305 USA. [Weitzman, Aaron] Genentech Inc, San Francisco, CA 94080 USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 N Grove St,Lawrence House 208, Boston, MA 02114 USA. EM tlynch@partners.org NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2008 VL 3 IS 6 SU S BP S107 EP S112 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 314SE UT WOS:000256828300001 PM 18520291 ER PT J AU Terhakopian, A Sinaii, N Engel, CC Schnurr, PP Hoge, CW AF Terhakopian, Artin Sinaii, Ninet Engel, Charles C. Schnurr, Paula P. Hoge, Charles W. TI Estimating population prevalence of posttraumatic stress disorder: An example using the PTSD Checklist SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID NATIONAL COMORBIDITY SURVEY; MENTAL-HEALTH PROBLEMS; DSM-IV DISORDERS; PRIMARY-CARE; PSYCHOMETRIC PROPERTIES; SCREENING INSTRUMENT; GENDER-DIFFERENCES; SURVEY REPLICATION; CIVILIAN VERSION; FEMALE VETERANS AB The PTSD Checklist (PCL) is among the most widely used self-report instruments for assessing PTSD. To determine PCL performance on a population level, the authors combined data from published studies that compared the PCL with structured diagnostic interviews. Weighted average sensitivities and specificities were calculated for cutoff categories most often reported in the literature. Weighted average sensitivity decreased from .85 to .39 and specificity increased from .73 to .97 for cutoffs ranging from 30 to 60. The PCL's ability to accurately estimate PTSD prevalence varied as a function of cutoff and true PTSD prevalence. In populations with a true PTSD prevalence of 15% or less, cutoff values below 44 will substantially overestimate PTSD prevalence. Uncalibrated use of the PCL for prevalence estimation may lead to large errors. C1 [Hoge, Charles W.] USA, Med Res & Mat Command, Walter Reed Army Inst Res, Div Psychiat & Neuroscience, Silver Spring, MD USA. [Terhakopian, Artin; Engel, Charles C.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stree, Bethesda, MD 20814 USA. [Sinaii, Ninet] NIH, Ctr Clin, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. [Schnurr, Paula P.] VA Med Ctr, Natl Ctr PTSD, White River Jct, VT USA. RP Hoge, CW (reprint author), USA, Med Res & Mat Command, Walter Reed Army Inst Res, Div Psychiat & Neuroscience, 503 Robert Grant Ave, Silver Spring, MD USA. EM charles.hoge@us.army.mil NR 47 TC 107 Z9 108 U1 2 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2008 VL 21 IS 3 BP 290 EP 300 DI 10.1002/jts.20341 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 317SF UT WOS:000257039300005 PM 18553416 ER PT J AU Arlen, PM Bianco, F Dahut, WL D'Amico, A Figg, WD Freedland, SJ Gulley, JL Kantoff, PW Kattan, MW Lee, A Regan, MM Sartor, O AF Arlen, Philip M. Bianco, Fernando Dahut, William L. D'Amico, Anthony Figg, William D. Freedland, Stephen J. Gulley, James L. Kantoff, Philip W. Kattan, Michael W. Lee, Andrew Regan, Meredith M. Sartor, Oliver TI Prostate specific antigen working group guidelines on prostate specific antigen doubling time SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; consensus; clinical trials as topic; biological markers ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; HORMONAL-THERAPY; MEN; SURVIVAL; RECURRENCE; CARCINOMA AB Purpose: Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells. Prostate specific antigen doubling time, or the change in prostate specific antigen over time, has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer. It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time, and to develop a common approach to outcome analysis and reporting. Materials and Methods: In September 20,06 a conference was held at the National Cancer Institute in Bethesda, Maryland to define these parameters and develop guidelines for their use. Results: The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time, evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials. Conclusions: We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity. We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome. Furthermore, the use of common standards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to randomized trials in which "hard" end points such as survival will be used. C1 [Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bianco, Fernando] George Washington Univ, Dept Urol, Washington, DC USA. [D'Amico, Anthony; Kantoff, Philip W.; Regan, Meredith M.; Sartor, Oliver] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony; Kantoff, Philip W.; Regan, Meredith M.; Sartor, Oliver] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Freedland, Stephen J.] Duke Univ, Div Urol, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Duke Prostate Ctr, Dept Surg, Durham, NC USA. [Kattan, Michael W.] Cleveland Clin, Cleveland, OH 44106 USA. [Lee, Andrew] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Freedland, Stephen J.] Duke Univ, Dept Pathol, Duke Prostate Ctr, Durham, NC USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; FU Intramural NIH HHS [Z01 BC010453-06]; NCI NIH HHS [Z01 BC010453] NR 20 TC 65 Z9 72 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2008 VL 179 IS 6 BP 2181 EP 2185 DI 10.1016/j.juro.2008.01.099 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 301SR UT WOS:000255916400025 PM 18423743 ER PT J AU Issaq, HJ Nativ, O Waybright, T Luke, B Veenstra, TD Issaq, EJ Kravstov, A Mullerad, M AF Issaq, Haleem J. Nativ, Ofer Waybright, Timothy Luke, Brian Veenstra, Timothy D. Issaq, Elias J. Kravstov, Alexander Mullerad, Michael TI Detection of bladder cancer in human urine by metabolomic profiling using high performance liquid chromatography/mass spectrometry SO JOURNAL OF UROLOGY LA English DT Article DE bladder; carcinoma; transitional cell; metabolism; chromatography; high pressure liquid; mass spectrometry ID MASS-SPECTROMETRY; CARCINOMA AB Purpose: The current use of cystoscopy for screening and detecting bladder cancer is invasive and expansive. Various urine based biomarkers have been used for this purpose with limited success. Metabolomics, ie metabonomics, is the quantitative measurement of the metabolic response to pathophysiological stimuli. This analysis provides a metabolite pattern that can be characteristic of various benign and malignant conditions. We evaluated high performance liquid chromatography coupled online with a mass spectrometer metabolomic approach to differentiate urine samples from healthy individuals and patients with bladder cancer. Materials and Methods: Urine specimens were collected from 48 healthy individuals and 41 patients with transitional cell carcinoma, and stored at -80C. Samples were analyzed using an Agilent 1100 Series high performance liquid chromatography system (Agilent Technologies, Santa Clara, California) coupled online with a hybrid triple-quad time-of-flight QSTAR(R) XL mass spectrometer. At the time of analysis samples were thawed and centrifuged. The resulting total ion chromatograms of each sample were submitted for statistical analysis. For data interpretation in this study 2 statistical methods were used, that is principal component analysis and orthogonal partial least square-discriminate analysis. Results: Using positive ionization mass spectrometry orthogonal partial least square-discriminate analysis correctly predicted 48 of 48 healthy and 41 of 41 bladder cancer urine samples, while principal component analysis, which is an unsupervised profiling statistical method, confirmed these results and correctly predicted 46 of 48 healthy and 40 of 41 bladder cancer urine samples. Conclusions: The results of this proof of concept study in a relatively small number of subjects indicate that metabolomics using high performance liquid chromatography-mass spectrometry has the potential to become a noninvasive early detection test for bladder cancer. C1 [Issaq, Haleem J.; Waybright, Timothy; Veenstra, Timothy D.] NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technologies, Frederick, MD 21702 USA. [Luke, Brian] NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Nativ, Ofer; Issaq, Elias J.; Kravstov, Alexander; Mullerad, Michael] Bnai Zion Med Ctr, Dept Urol, Haifa, Israel. RP Issaq, HJ (reprint author), NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technologies, POB B, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 20 TC 79 Z9 82 U1 5 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2008 VL 179 IS 6 BP 2422 EP 2426 DI 10.1016/j.juro.2008.01.084 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 301SR UT WOS:000255916400096 PM 18433783 ER PT J AU Dabire, KR Diabate, A Pare-Toe, L Rouamba, J Ouari, A Fontenille, D Baldet, T AF Dabire, K. R. Diabate, A. Pare-Toe, L. Rouamba, J. Ouari, A. Fontenille, D. Baldet, T. TI Year to year and seasonal variations in vector bionomics and malaria transmission in a humid savannah village in west Burkina Faso SO JOURNAL OF VECTOR ECOLOGY LA English DT Article DE Anopheles funestus; Anopheles gambiae s.s; malaria transmission; semi-permanent swamp; Burkina Faso ID ANOPHELES-GAMBIAE COMPLEX; POLYMERASE-CHAIN-REACTION; SOUTH CAMEROON; IDENTIFICATION; CULICIDAE; DIPTERA; ELISA; ASSAY AB A longitudinal entomological study was carried out from 1999 to 2001 in Lena, a humid savannah village in the western region of Burkina Faso in order to establish malaria vector bionomics and the dynamics of malaria transmission. In the first year, malaria transmission was mainly due to An. gambiae s.s., but during the two later years was due to An. funestus, which were observed in high frequency towards the end of the rainy season. PCR identification of samples of An. gambiae s.l. showed 93% to be An. gambiae s.s. and 7% An. arabiensis. An. funestus constituting more than 60% of the vectors were identified in PCR as An. funestus s.s. The persistence of intense vectorial activity in this village was probably due to the road building in a swampy area creating a semi-permanent swamp that provided large sites for larval mosquitoes. These swampy sites seemed to be more favorable for An. funestus than for An. gambiae s.s. Thus, land development must be monitored and subjected to planning to minimize vector proliferation. Such a system of planning could lead to the restriction or even elimination of the swamp that is the source of larvae developing in the heart of the village. C1 [Dabire, K. R.; Diabate, A.; Pare-Toe, L.; Rouamba, J.; Ouari, A.] Ctr Muraz, IRSS, Bobo Dioulasso, Burkina Faso. [Diabate, A.] NIAID, Lab Malaria & Vector Res, NIH, Washington, DC USA. [Fontenille, D.] Lab Lutte Contre Insectes Nuisibles LIN IRD, F-34032 Montpellier 1, France. [Baldet, T.] Cirad UPR16, Montpellier, France. RP Dabire, KR (reprint author), Ctr Muraz, IRSS, BP 392, Bobo Dioulasso, Burkina Faso. RI FONTENILLE, didier/G-4091-2013 NR 19 TC 7 Z9 7 U1 0 U2 0 PU SOC VECTOR ECOLOGY PI CORONA PA 1966 COMPTON AVE, CORONA, CA 92881 USA SN 1081-1710 J9 J VECTOR ECOL JI J. Vector Ecol. PD JUN PY 2008 VL 33 IS 1 BP 70 EP 75 DI 10.3376/1081-1710(2008)33[70:YTYASV]2.0.CO;2 PG 6 WC Entomology SC Entomology GA 325MD UT WOS:000257592100009 PM 18697309 ER PT J AU Wagenaar, TR Ojeda, S Moss, B AF Wagenaar, Timothy R. Ojeda, Suany Moss, Bernard TI Vaccinia virus A56/K2 fusion regulatory protein interacts with the A16 and G9 subunits of the entry fusion complex SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CELL-FUSION; VIRION MEMBRANE-PROTEIN; INFECTED-CELLS; ESSENTIAL COMPONENT; POXVIRUS ENTRY; GENE ENCODES; HEMAGGLUTININ; INHIBITOR; ENVELOPE; SPI-3 AB Deletion of the A56R or K2L gene of vaccinia virus (VACV) results in the spontaneous fusion of infected cells to form large multinucleated syncytia. A56 and K2 polypeptides bind to one another (A56/K2) and together are required for interaction with the VACV entry fusion complex (EFC); this association has been proposed to prevent the fusion of infected cells. At least eight viral polypeptides comprise the EFC, but no information has been available regarding their interactions either with each other or with A56/K2. Utilizing a panel of recombinant VACVs designed to repress expression of individual EFC subunits, we demonstrated that A56/K2 interacted with two polypeptides: A16 and G9. Both A16 and G9 were required for the efficient binding of each to A56/K2, suggesting that the two polypeptides interact with each other within the EFC. Such an interaction was established by the copurification of A16 and G9 from infected cells under conditions in which a stable EFC complex failed to assemble and from detergent-treated lysates of uninfected cells that coexpressed A16 and G9. A recombinant VACV that expressed G9 modified with an N-terminal epitope tag induced the formation of syncytia, suggesting partial interference with the functional interaction of A56/K2 with the EFC during infection. These data suggest that A16 and G9 are physically associated within the EFC and that their interaction with A56/K2 suppresses spontaneous syncytium formation and possibly "fuse-back" superinfection of cells. C1 [Wagenaar, Timothy R.; Ojeda, Suany; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Wagenaar, Timothy R.] Univ Maryland, College Pk, MD 20742 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 38 TC 20 Z9 23 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 JUN PY 2008 VL 82 IS 11 BP 5153 EP 5160 DI 10.1128/JVI.00162-08 PG 8 WC Virology SC Virology GA 301FN UT WOS:000255881900005 PM 18353946 ER PT J AU Buck, CB Cheng, N Thompson, CD Lowy, DR Steven, AC Schiller, JT Trus, BL AF Buck, Christopher B. Cheng, Naiqian Thompson, Cynthia D. Lowy, Douglas R. Steven, Alasdair C. Schiller, John T. Trus, Benes L. TI Arrangement of L2 within the papillomavirus capsid SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; PROTEIN L2; LIFE-CYCLE; L1 PROTEIN; NEUTRALIZATION; INFECTION; BOVINE; EXPRESSION; MODEL; IDENTIFICATION AB Papillomaviruses are a family of nonenveloped DNA tumor viruses. Some sexually transmitted human papillomavirus (HPV) types, including HPV type 16 (HPV16), cause cancer of the uterine cervix. Papillomaviruses encode two capsid proteins, L1 and L2. The major capsid protein, L1, can assemble spontaneously into a 72-pentamer icosahedral structure that closely resembles native virions. Although the minor capsid protein, L2, is not required for capsid formation, it is thought to participate in encapsidation of the viral genome and plays a number of essential roles in the viral infectious entry pathway. The abundance of L2 and its arrangement within the virion remain unclear. To address these questions, we developed methods for serial propagation of infectious HPV16 capsids (pseudoviruses) in cultured human cell lines. Biochemical analysis of capsid preparations produced using various methods showed that up to 72 molecules of L2 can be incorporated per capsid. Cryoelectron microscopy and image reconstruction analysis of purified capsids revealed an icosahedrally ordered U-specific density beneath the axial lumen of each L1 capsomer. The relatively close proximity of these L2 density buttons to one another raised the possibility of homotypic L2 interactions within assembled virions. The concept that the N and C termini of neighboring L2 molecules can be closely apposed within the capsid was supported using bimolecular fluorescence complementation or "split GFP" technology. This structural information should facilitate investigation of L2 function during the assembly and entry phases of the papillomavirus life cycle. C1 [Cheng, Naiqian; Steven, Alasdair C.; Trus, Benes L.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Buck, Christopher B.; Thompson, Cynthia D.; Lowy, Douglas R.; Schiller, John T.] Natl Canc Inst, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Trus, Benes L.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Trus, Benes L.] Ctr Informat Technol, Imaging Sci Lab, Bethesda, MD 20892 USA. RP Trus, BL (reprint author), NIAMSD, Struct Biol Res Lab, NIH, 12 Ctr Dr,MSC 5624, Bethesda, MD 20892 USA. EM Benes_Trus@nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS NR 54 TC 136 Z9 144 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 11 BP 5190 EP 5197 DI 10.1128/JVI.02726-07 PG 8 WC Virology SC Virology GA 301FN UT WOS:000255881900009 PM 18367526 ER PT J AU Maximova, OA Ward, JM Asher, DM Claire, MS Finneyfrock, BW Speicher, JM Murphy, BR Pletnev, AG AF Maximova, Olga A. Ward, Jerrold M. Asher, David M. Claire, Marisa St. Finneyfrock, Brad W. Speicher, James M. Murphy, Brian R. Pletnev, Alexander G. TI Comparative neuropathogenesis and neurovirulence of attenuated flaviviruses in nonhuman primates SO JOURNAL OF VIROLOGY LA English DT Article ID TICK-BORNE ENCEPHALITIS; GROUP-B ARBOVIRUSES; CENTRAL NERVOUS-SYSTEM; DENGUE TYPE-4 VIRUSES; MONKEY NEUROVIRULENCE; VACCINE CANDIDATE; RHESUS-MONKEYS; MONOCLONAL-ANTIBODIES; LANGAT VIRUS; LIVE AB Based on previous preclinical evaluation in mice and monkeys, the chimeric TBEV/DEN4 Delta 30 virus, carrying the prM and E protein genes from a highly virulent Far Eastern strain of tick-borne encephalitis virus (TBEV) on the backbone of a nonneuroinvasive dengue type 4 virus (DEN4), has been identified as a promising live attenuated virus vaccine candidate against disease caused by TBEV. However, prior to use of this vaccine candidate in humans, its neurovirulence in nonhuman primates needed to be evaluated. In the present study, we compared the neuropathogeneses of the chimeric TBEV/DEN4 Delta 30 virus; Langat virus (LGTV), a former live TBEV vaccine; and yellow fever 17D virus vaccine (YF 17D) in rhesus monkeys inoculated intracerebrally. TBEV/DEN4 Delta 30 and YF 17D demonstrated remarkably similar spatiotemporal profiles of virus replication and virus-associated histopathology in the central nervous system (CNS) that were high in cerebral hemispheres but progressively decreased toward the spinal cord. In contrast, the neurovirullence of LGTV exhibited the reverse profile, progressing from the site of inoculation toward the cerebellum and spinal cord. Analysis of the spatiotemporal distribution of viral antigens in the CNS of monkeys revealed a prominent neurotropism associated with all three attenuated viruses. Nevertheless, TBEV/DEN4 Delta 30 virus exhibited higher neurovirulence in monkeys than either LGTV or YF 17D, suggesting insufficient attenuation. These results provide insight into the neuropathogenesis associated with attenuated flaviviruses that may guide the design of safe vaccines. C1 [Speicher, James M.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Maximova, Olga A.; Asher, David M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Claire, Marisa St.; Finneyfrock, Brad W.] Bioqual Inc, Rockville, MD 20850 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,Room 3W10A,MSC 3203, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 21 Z9 21 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 JUN PY 2008 VL 82 IS 11 BP 5255 EP 5268 DI 10.1128/JVI.00172-08 PG 14 WC Virology SC Virology GA 301FN UT WOS:000255881900015 PM 18353947 ER PT J AU Frank, I Stossel, H Gettie, A Turville, SG Bess, JW Lifson, JD Sivin, I Romani, N Robbiani, M AF Frank, I. Stoessel, H. Gettie, A. Turville, S. G. Bess, J. W., Jr. Lifson, J. D. Sivin, I. Romani, N. Robbiani, M. TI Fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells SO JOURNAL OF VIROLOGY LA English DT Article ID DC-SIGN; HIV-1 INFECTION; ANTIGEN PRESENTATION; TRANS-INFECTION; RETROVIRAL INFECTIVITY; TYPE-1 REPLICATION; LANGERHANS CELLS; TRANSMISSION; MATURE; IMMATURE AB Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4(+) T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4(+), not CD8(+), T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites. This occurred within 5 min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus capture by DCs or the release of viruses at the DC-T-cell contact points, it readily blocked virus transfer to and amplification in CD4(+) T cells. Higher doses of T-1249 were needed to block the more robust replication driven by mature DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were actually less infectious than DCs isolated from untreated cocultures. Importantly, T-1249 did not interfere with the stimulation of virus-specific CD4(+) and CD8(+) T-cell responses when present during virus-loading of DCs or for the time of the DC-T-cell coculture. These results provide clues to identifying strategies to prevent DC-driven virus amplification in CD4(+) T cells while maintaining virus-specific immunity, an objective critical in the development of microbicides and therapeutic vaccines. C1 [Frank, I.; Turville, S. G.; Sivin, I.; Robbiani, M.] Populat Council, HIV & AIDS Program, Ctr Biomed Res, New York, NY 10065 USA. [Gettie, A.] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. [Stoessel, H.; Romani, N.] Innsbruck Med Univ, Dept Dermatol, Innsbruck, Austria. [Bess, J. W., Jr.; Lifson, J. D.] NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. RP Robbiani, M (reprint author), Populat Council, HIV & AIDS Program, Ctr Biomed Res, 1230 York Ave, New York, NY 10065 USA. EM mrobbiani@popcouncil.org FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NCRR NIH HHS [RR00164, P51 RR000164]; NIAID NIH HHS [AI040877, AI065412, P01 AI052048, R37 AI040877, U19 AI065413, U19 AI065412, R01 AI040877, AI065413, AI052048]; NICHD NIH HHS [P01 HD041752, HD041752] NR 70 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 11 BP 5329 EP 5339 DI 10.1128/JVI.01987-07 PG 11 WC Virology SC Virology GA 301FN UT WOS:000255881900021 PM 18367527 ER PT J AU Jarman, RG Holmes, EC Rodpradit, P Klungthong, C Gibbons, RV Nisalak, A Rothman, AL Libraty, DH Ennis, FA Mammen, MP Endy, TP AF Jarman, Richard G. Holmes, Edward C. Rodpradit, Prinyada Klungthong, Chonticha Gibbons, Robert V. Nisalak, Ananda Rothman, Alan L. Libraty, Daniel H. Ennis, Francis A. Mammen, Mammen P., Jr. Endy, Timothy P. TI Microevolution of dengue viruses circulating among primary school children in Kamphaeng Phet, Thailand SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CULTURES; IDENTIFICATION; INFECTION; SELECTION; EVOLUTION; TYPE-2 AB To determine the extent and structure of genetic variation in dengue viruses (DENV) on a restricted spatial and temporal scale, we sequenced the E (envelope) genes of DENY-1, -2, and -3 isolates collected in 2001 from children enrolled in a prospective school-based study in Kamphaeng Phet, Thailand, and diagnosed with dengue disease. Our analysis revealed substantial viral genetic variation in both time and space, with multiple viral lineages circulating within individual schools, suggesting the frequent gene flow of DENV into this microenvironment. More-detailed analyses of DENV-2 samples revealed strong clustering of viral isolates within individual schools and evidence of more-frequent viral gene flow among schools closely related in space. Conversely, we observed little evolutionary change in those viral isolates sampled over multiple time points within individual schools, indicating a low rate of mutation fixation. These results suggest that frequent viral migration into Kamphaeng Phet, coupled with population (school) subdivision, shapes the genetic diversity of DENV on a local scale, more so than in situ evolution within school catchment areas. C1 [Jarman, Richard G.] USAMC, Dept Virol, AFRIMS, APO, AP 96546 USA. [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rothman, Alan L.; Libraty, Daniel H.; Ennis, Francis A.] Univ Massachusetts, Sch Med, Ctr Infect Dis & Vaccine Res, Worcester, MA 01655 USA. [Endy, Timothy P.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Jarman, Richard G.; Rodpradit, Prinyada; Klungthong, Chonticha; Gibbons, Robert V.; Nisalak, Ananda; Mammen, Mammen P., Jr.] USAMC, Dept Virol, Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. RP Jarman, RG (reprint author), USAMC, Dept Virol, AFRIMS, APO, AP 96546 USA. EM Richard.Jarman@afrims.org OI Holmes, Edward/0000-0001-9596-3552 FU NIAID NIH HHS [P01 AI034533, P01-AI34533] NR 22 TC 36 Z9 36 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 11 BP 5494 EP 5500 DI 10.1128/JVI.02728-07 PG 7 WC Virology SC Virology GA 301FN UT WOS:000255881900037 PM 18367520 ER PT J AU Veazey, RS Acierno, PM McEvers, KJ Baumeister, SHC Foster, GJ Rett, MD Newberg, MH Kuroda, MJ Williams, K Kim, EY Wolinsky, SM Rieber, EP Piatak, M Lifson, JD Montefiori, DC Brown, CR Hirsch, VA Schmitz, JE AF Veazey, Ronald S. Acierno, Paula M. McEvers, Kimberly J. Baumeister, Susanne H. C. Foster, Gabriel J. Rett, Melisa D. Newberg, Michael H. Kuroda, Marcelo J. Williams, Kenneth Kim, Eun-Young Wolinsky, Steven M. Rieber, E. Peter Piatak, Michael, Jr. Lifson, Jeffrey D. Montefiori, David C. Brown, Charles R. Hirsch, Vanessa A. Schmitz, Jm E. TI Increased loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted simian immunodeficiency virus-infected rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID RAPID PROGRESSOR MACAQUES; ACUTE SIV INFECTION; HIV-INFECTION; IN-VIVO; GASTROINTESTINAL-TRACT; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; CHEMOKINE RECEPTORS; IMMUNE-RESPONSES; MEMORY AB Previously we have shown that CD8(+) T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4(+) T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8(+) T-cell responses on the magnitude of the CD4(+) T-cell depletion, we investigated the effect of CD8(+) lymphocyte depletion during primary SIV infection on CD4(+) T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8(+) lymphocyte-depletion changed the dynamics of CD4(+) T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4(+) T cells were restored to baseline levels. These CD4(+) T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8(+) lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4(+) T cells were eliminated more efficiently in CD8(+) lymphocyte-depleted animals. Also, CD8(+) lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4(+) T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8(+) T-cell responses are absolutely critical to initiate at least partial control of SIV infection. C1 [Acierno, Paula M.; McEvers, Kimberly J.; Baumeister, Susanne H. C.; Foster, Gabriel J.; Rett, Melisa D.; Newberg, Michael H.; Williams, Kenneth; Schmitz, Jm E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Veazey, Ronald S.; Kuroda, Marcelo J.] Tulane Univ, Sch Med, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Kim, Eun-Young; Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Rieber, E. Peter] Tech Univ Dresden, Inst Immunol, D-01101 Dresden, Germany. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Brown, Charles R.; Hirsch, Vanessa A.] NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Schmitz, JE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, RE 213D,41 Ave Louis Pasteur, Boston, MA 02115 USA. EM jschmitz@bidmc.harvard.edu RI Wolinsky, Steven/B-2893-2012 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [R24 RR016001, RR016001]; NIAID NIH HHS [R01 AI048394, AI040101, AI060354, AI065335, AI48394, AI49080, P30 AI060354, R01 AI040101, R01 AI049080, R01 AI065335] NR 78 TC 20 Z9 20 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 11 BP 5618 EP 5630 DI 10.1128/JVI.02748-07 PG 13 WC Virology SC Virology GA 301FN UT WOS:000255881900049 PM 18367534 ER PT J AU Kim, EY Veazey, RS Zahn, R McEvers, KJ Baumeister, SHC Foster, GJ Rett, MD Newberg, MH Kuroda, MJ Rieber, EP Piatak, M Lifson, JD Letvin, NL Wolinsky, SM Schmitz, JE AF Kim, Eun-Young Veazey, Ronald S. Zahn, Roland McEvers, Kimberly J. Baumeister, Susanne H. C. Foster, Gabriel J. Rett, Melisa D. Newberg, Michael H. Kuroda, Marcelo J. Rieber, E. Peter Piatak, Michael, Jr. Lifson, Jeffrey D. Letvin, Norman L. Wolinsky, Steven M. Schmitz, Joern E. TI Contribution of CD8(+) T cells to containment of viral replication and emergence of mutations in Mamu-A*01-restricted epitopes in simian immunodeficiency virus-infected rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULE; MHC CLASS-I; MONOCLONAL-ANTIBODY; LYMPHOCYTES; VIREMIA; ESCAPE; AIDS; CLEARANCE; RESPONSES AB Here, we investigated the containment of virus replication in simian immunodeficiency virus (SIV) infection by CD8(+) lymphocytes. Escape mutations in Mamu-A*01 epitopes appeared first in SIV Tat TL8 and then in SIV Gag p11C. The appearance of escape mutations in SIV Gag p11C was coincident with compensatory changes outside of the epitope. Eliminating CD8(+) lymphocytes from rhesus monkeys during primary infection resulted in more rapid disease progression that was associated with preservation of canonical epitopes. These results confirm the importance of cytotoxic T cells in controlling viremia and the constraint on epitope sequences that require compensatory changes to go to fixation. C1 [Kim, Eun-Young; Wolinsky, Steven M.] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA. [Veazey, Ronald S.; Kuroda, Marcelo J.] Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Zahn, Roland; McEvers, Kimberly J.; Baumeister, Susanne H. C.; Foster, Gabriel J.; Rett, Melisa D.; Newberg, Michael H.; Letvin, Norman L.; Schmitz, Joern E.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Rieber, E. Peter] Tech Univ Dresden, Inst Immunol, D-01101 Dresden, Germany. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDD Vaccine Program, SAIC Fredrick Inc, Frederick, MD 21702 USA. RP Kim, EY (reprint author), Northwestern Univ, Div Infect Dis, Feinberg Sch Med, 676 N St,Clair St,Suite 200, Chicago, IL 60611 USA. EM e-kim@northwestern.edu; jschmitz@bidmc.harvard.edu RI Wolinsky, Steven/B-2893-2012 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [R24 RR016001, RR016001]; NIAID NIH HHS [AI040101, AI060354, AI065335, AI20729, AI48394, P30 AI060354, R01 AI020729, R01 AI040101, R01 AI048394, R01 AI065335, R37 AI020729] NR 18 TC 17 Z9 17 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 11 BP 5631 EP 5635 DI 10.1128/JV1.02749-07 PG 5 WC Virology SC Virology GA 301FN UT WOS:000255881900050 PM 18367519 ER PT J AU Mulky, A Cohen, TV Kozlov, SV Korbei, B Foisner, R Stewart, CL KewalRarnani, VN AF Mulky, Alok Cohen, Tatiana V. Kozlov, Serguei V. Korbei, Barbara Foisner, Roland Stewart, Colin L. KewalRarnani, Vineet N. TI The LEM domain proteins emerin and LAP2 alpha are dispensable for human immunodeficiency virus type 1 and murine leukemia virus infections SO JOURNAL OF VIROLOGY LA English DT Article ID TO-AUTOINTEGRATION FACTOR; NUCLEAR-MEMBRANE PROTEIN; HIV-1 INTEGRASE; PREINTEGRATION COMPLEXES; LEDGF/P75; BARRIER; BINDING; DNA; IDENTIFICATION; REVEALS AB The human nuclear envelope proteins emerin and lamina-associated polypeptide 2 alpha (LAP2 alpha) have been proposed to aid in the early replication steps of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). However, whether these factors are essential for HIV-1 or MLV infection has been questioned. Prior studies in which conflicting results were obtained were highly dependent on RNA interference-mediated gene silencing. To shed light on these contradictory results, we examined whether HIV-1 or MLV could infect primary cells from mice deficient for emerin, LAP2 alpha, or both emerin and LAP2 alpha. We observed HIV-1 and MLV infectivity in mouse embryonic fibroblasts (MEFs) from emerin knockout, LAP2 alpha knockout, or emerin and LAP2 alpha double knockout mice to be comparable in infectivity to wild-type littermate-derived MEFs, indicating that both emerin and LAP2 alpha were dispensable for HIV-1 and MLV infection of dividing, primary mouse cells. Because emerin has been suggested to be important for infection of human macrophages by HIV-1, we also examined HIV-1 transduction of macrophages from wild-type mice or knockout mice, but again we did not observe a difference in susceptibility. These findings prompted us to reexamine the role of human emerin in supporting HIV-1 and MLV infection. Notably, both viruses efficiently infected human cells expressing high levels of dominant-negative emerin. We thus conclude that emerin and LAP2 alpha are not required for the early replication of HIV-1 and MLV in mouse or human cells. C1 [Mulky, Alok; KewalRarnani, Vineet N.] NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. [Cohen, Tatiana V.; Kozlov, Serguei V.; Stewart, Colin L.] NCI, Canc & Dev Biol Lab, Ft Detrick, MD 21702 USA. [Korbei, Barbara; Foisner, Roland] Med Univ Vienna, Dept Med Biochem, Max F Perutz Labs, A-1030 Vienna, Austria. RP KewalRarnani, VN (reprint author), NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. EM colin.stewart@imb.a-star.edu.sg; vineet@ncifcrf.gov OI Korbei, Barbara/0000-0002-0439-0435 FU Intramural NIH HHS NR 38 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 12 BP 5860 EP 5868 DI 10.1128/JVI.00076-08 PG 9 WC Virology SC Virology GA 309IJ UT WOS:000256453600018 PM 18400857 ER PT J AU Cao, DJ Barroj, M Hoshino, Y AF Cao, Dianjun Barroj, Mario Hoshino, Yasutaka TI Porcine rotavirus bearing an aberrant gene stemming from an intergenic recombination of the NSP2 and NSP5 genes is defective and interfering SO JOURNAL OF VIROLOGY LA English DT Article ID BOVINE ROTAVIRUS; GENOME REARRANGEMENTS; INFLUENZA-VIRUS; REASSORTMENT; CLONING AB Serial undiluted passage of a porcine rotavirus in MA104 cells yielded three distinct virus populations, each of which bore different rearranged genes. Sequencing revealed that each of two populations bore a distinct intragenic recombinant NSP3 gene consisting of a partial duplication in a head-to-tail orientation without altering the NSP3 open reading frame and the third population carried both an intragenic recombinant NSP3 gene and an intergenic recombinant gene (1,647 nucleotides in length) which contained a truncated NSP2 gene inserted into the NSP5 gene at residue 332. The former two populations were viable, whereas the latter population was defective and interfering. C1 [Cao, Dianjun; Barroj, Mario; Hoshino, Yasutaka] NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Rm 6308,50 South Dr,MSC 8026, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000966-02] NR 20 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 12 BP 6073 EP 6077 DI 10.1128/JVI.00121-08 PG 5 WC Virology SC Virology GA 309IJ UT WOS:000256453600042 PM 18417592 ER PT J AU Castle, PE AF Castle, Philip E. TI How does tobacco smoke contribute to cervical carcinogenesis? SO JOURNAL OF VIROLOGY LA English DT Letter ID HUMAN-PAPILLOMAVIRUS TYPES; WOMEN; RISK C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5004,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov NR 10 TC 7 Z9 7 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 JUN PY 2008 VL 82 IS 12 BP 6084 EP 6085 DI 10.1128/JVI.00103-08 PG 2 WC Virology SC Virology GA 309IJ UT WOS:000256453600044 PM 18497423 ER PT J AU Grim, KC McCutchan, T Sullivan, M Cranfield, MR AF Grim, K. Christiana McCutchan, Thomas Sullivan, Margery Cranfield, Michael R. TI Unidentified plasmodium species in Australian black swans (Cygnus atratus) hatched and raised in North America SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE avian malaria; Australian black swan; Cygnus atratus; Plasmodium ID PENGUINS SPHENISCUS-DEMERSUS; AVIAN MALARIA; PARASITE; IDENTIFICATION; MORTALITY; ELONGATUM AB A pair of Australian black swans (Cygnus atratus) with origins in Wakefield, Virginia, USA, was admitted to the quarantine area at the Baltimore Zoo for general health assessments before housing in the collections. During the quarantine period, no clinical signs of disease were manifest; however, upon examination of a blood smear, intra-erythrocytic parasites were detected and initially determined to be Haemoproteus species. Diagnostic polymerase chain reaction (PCR) and sequencing results, however, indicated that the parasites were within the genus Plasmodium. Subclinical infections with Plasmodium species in birds may affect collection management, and transmission from refractory hosts to susceptible hosts should be considered when multispecies exhibits are used. In addition, changes in the dynamics of host-vector-parasite interactions might have significant impacts on wild or domesticated populations of birds. C1 [Grim, K. Christiana; McCutchan, Thomas; Sullivan, Margery] NIAID, NIH, Rockville, MD 20822 USA. [Cranfield, Michael R.] Baltimore Zoo, Dept Med, Baltimore, MD 21217 USA. [Cranfield, Michael R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Comparat Med, Baltimore, MD 21205 USA. RP Grim, KC (reprint author), US EPA, 1200 Penn Ave,NW,Ariel Rios 7203M, Washington, DC 20460 USA. EM grim.christiana@epa.gov NR 20 TC 2 Z9 2 U1 1 U2 4 PU AMER ASSOC ZOO VETERINARIANS PI YULEE PA 581705 WHITE OAK ROAD, YULEE, FL 32097 USA SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD JUN PY 2008 VL 39 IS 2 BP 216 EP 220 DI 10.1638/2007-0110R.1 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 304JR UT WOS:000256106300010 PM 18634212 ER PT J AU Morley, JE Ferrucci, L AF Morley, John E. Ferrucci, Luigi TI Publication productivity in geriatrics: 1995-2006 SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID FUTURE HISTORY; ANTIAGING MEDICINE C1 [Morley, John E.] St Louis Univ, Med Ctr, Div Geriatr Med, St Louis, MO 63104 USA. [Morley, John E.] VA Med Ctr GRECC, St Louis, MO USA. [Ferrucci, Luigi] NIA, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Morley, JE (reprint author), St Louis Univ, Med Ctr, Div Geriatr Med, 1402 S Grand Blvd,M238, St Louis, MO 63104 USA. EM morley@slu.edu RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 FU Intramural NIH HHS [Z01 AG000015-49] NR 15 TC 3 Z9 3 U1 0 U2 0 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 JUN PY 2008 VL 63 IS 6 BP 584 EP 585 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 318IH UT WOS:000257084300006 PM 18559631 ER PT J AU Newman, AB Boudreau, RM Naydeck, BL Fried, LF Harris, TB AF Newman, Anne B. Boudreau, Robert M. Naydeck, Barbara L. Fried, Linda F. Harris, Tamara B. TI A physiologic index of comorbidity: Relationship to mortality and disability SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE disability; mortality; comorbidity ID CARDIOVASCULAR HEALTH; BODY-COMPOSITION; OLDER-ADULTS; ROC CURVES; DISEASE; PEOPLE; RISK; ATHEROSCLEROSIS; ASSOCIATIONS; DEPRESSION AB Background. In older adults, there is often substantial undiagnosed chronic disease detectable on noninvasive testing, not accounted for by most comorbidity indices. We developed a simple physiologic index of comorbidity by scoring five noninvasive tests across the full range of values. We examined the predictive validity of this index for mortality and disability. Methods. There were 2928 (mean age 74.5 years, 60% women, 85% white, and 15% black) participants in the Cardiovascular Health Study (1992-1993) who had carotid ultrasound, pulmonary function testing, brain magnetic resonance scan, serum cystatin-C, and fasting glucose. These were combined into a single physiologic index of comorbid chronic disease on a scale of 0-10. Cox proportional hazard models were used to predict mortality, mobility limitation, and activities of daily living (ADL) difficulty after a maximum of 9 years. Results. The range of the physiologic index was quite broad, with very few individuals having total scores of either 0 or 10. Those with an index of 7-10 had a hazard ratio of 3.80 (95% confidence interval, 2.82-5.13) for mortality compared to those with scores of 0-2, after adjustment for demographics, behavioral risk factors, and clinically diagnosed conditions. Associations with mobility limitation and ADL difficulty were also significant. The index explained about 40% of the age effect on mortality risk. Conclusion. Older adults with low levels of markers of chronic disease are rather rare but have remarkably good health outcomes. The ability of such an index to distinguish usual from low risk might provide an opportunity to better understand optimal health in old age. C1 [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Dept Epidemiol, 130 N Bellefield Ave,Room 532, Pittsburgh, PA 15213 USA. EM newmana@edc.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU NHLBI NIH HHS [N01 HC-55222, N01 HC015103, N01 HC035129, N01 HC045133, N01-HC-75150, N01-HC-85079, N01-HC-85086, N01HC55222, N01HC75150, N01HC85079, N01HC85086, U01 HL080295]; NIA NIH HHS [R01 AG023629-01, 5-P30-AG-024827, P30 AG024827, R01 AG023629, R01 AG023629-02, R01 AG023629-03, R01 AG023629-04, R01-AG-023629] NR 38 TC 48 Z9 49 U1 4 U2 6 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 JUN PY 2008 VL 63 IS 6 BP 603 EP 609 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 318IH UT WOS:000257084300010 PM 18559635 ER PT J AU Doi, K Hu, X Yuen, PST Leelahavanichkul, A Yasuda, H Kim, SM Schnermann, J Jonassen, TEN Frokiaer, J Nielsen, S Star, RA AF Doi, K. Hu, X. Yuen, P. S. T. Leelahavanichkul, A. Yasuda, H. Kim, S. M. Schnermann, J. Jonassen, T. E. N. Frokiaer, J. Nielsen, S. Star, R. A. TI AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality SO KIDNEY INTERNATIONAL LA English DT Article DE apoptosis; hemodynamics; spleen; telemetry ID ACUTE-RENAL-FAILURE; POLYMICROBIAL SEPSIS; MELANOCORTIN PEPTIDES; INFLAMMATORY RESPONSE; ORGAN DYSFUNCTION; CECAL LIGATION; SEPTIC SHOCK; NITRIC-OXIDE; DNA-DAMAGE; AGED MICE AB Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. alpha-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new alpha-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 h after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-alpha and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-kappa B activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. C1 [Doi, K.; Hu, X.; Yuen, P. S. T.; Leelahavanichkul, A.; Yasuda, H.; Kim, S. M.; Schnermann, J.; Star, R. A.] NIDDK, NIH, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. [Jonassen, T. E. N.] Univ Copenhagen, Dept Pharmacol, Copenhagen, Denmark. [Jonassen, T. E. N.; Frokiaer, J.; Nielsen, S.] Act Pharma, Aarhus, Denmark. [Frokiaer, J.; Nielsen, S.] Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark. RP Star, RA (reprint author), NIDDK, NIH, Renal Diagnost & Therapeut Unit, 10 Ctr Dr,Room 3N108, Bethesda, MD 20892 USA. EM robert_star@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z01 DK043403-08] NR 58 TC 62 Z9 65 U1 0 U2 1 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 JUN PY 2008 VL 73 IS 11 BP 1266 EP 1274 DI 10.1038/ki.2008.97 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 301LJ UT WOS:000255897400009 PM 18354376 ER PT J AU Menon, V Wang, X Sarnak, MJ Hunsicker, LH Madero, M Beck, GJ Collins, AJ Kusek, JW Levey, AS Greene, T AF Menon, V. Wang, X. Sarnak, M. J. Hunsicker, L. H. Madero, M. Beck, G. J. Collins, A. J. Kusek, J. W. Levey, A. S. Greene, T. TI Long-term outcomes in nondiabetic chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Nephrology CY NOV 14-19, 2006 CL San Diego, CA SP Amer Soc Nephrol DE chronic kidney disease; epidemiology; outcomes ID STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; HYPERTENSIVE PATIENTS; RISK; POPULATION AB The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease. C1 [Menon, V.; Sarnak, M. J.; Madero, M.; Levey, A. S.] Tufts Univ New England Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Wang, X.; Beck, G. J.] Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH USA. [Hunsicker, L. H.] Univ Iowa Hlth Care, Dept Internal Med, Iowa City, IA USA. [Collins, A. J.] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. [Kusek, J. W.] NIH, Bethesda, MD 20892 USA. [Greene, T.] Univ Utah, Div Clin Epidemiol, Salt Lake City, UT USA. RP Menon, V (reprint author), 750 Washington Str,No 391, Boston, MA 02111 USA. EM vmenon@tufts-nemc.org FU NIDDK NIH HHS [K23 DK02904, UO1 DK35073, K23 DK067303] NR 16 TC 46 Z9 48 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2008 VL 73 IS 11 BP 1310 EP 1315 DI 10.1038/ki.2008.67 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 301LJ UT WOS:000255897400015 PM 18337713 ER PT J AU Feldman, BM Rider, LG Reed, AM Pachman, LM AF Feldman, Brian M. Rider, Lisa G. Reed, Ann M. Pachman, Lauren M. TI Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood SO LANCET LA English DT Review ID NECROSIS-FACTOR-ALPHA; BONE-MINERAL DENSITY; INTERNATIONAL CONSENSUS; CLINICAL CHARACTERISTICS; DISEASE-ACTIVITY; AMYOPATHIC DERMATOMYOSITIS; INTRAVENOUS IMMUNOGLOBULIN; MACROPHAGIC MYOFASCIITIS; PEDIATRIC RHEUMATOLOGY; CHRONIC POLYMYOSITIS AB Juvenile dermatomyositis, the most common inflammatory myopathy of childhood, is a rare systemic autoimmune vasculopathy that is characterised by weakness in proximal muscles and pathognomonic skin rashes. The length of time before the initiation of treatment affects presenting symptoms, laboratory measures, and pathophysiology. It also affects disease outcomes, including the development of pathological calcifications, which are associated with increased morbidity. Both genetic and environmental risk factors seem to have a role in the cause of juvenile dermatomyositis; HLA B8-DRB1*0301 ancestral haplotype is a strong immunogenetic risk factor, and antecedent infections and birth seasonality suggest that environmental stimuli might increase risk. Activation of dendritic cells with upregulation of genes induced by type-1 interferon (alpha) in muscle and peripheral blood seems to be central to disease pathogenesis. Treatment often includes combinations of corticosteroids, methotrexate, and other immunosuppressive agents. Disease outcome, if treatment is initiated early, is generally good. Randomised controlled trials are needed to define the most effective treatments. C1 [Feldman, Brian M.] Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Pediat, Toronto, ON M5G 1X8, Canada. [Feldman, Brian M.] Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Hlth Policy Management & Evaulat, Toronto, ON M5G 1X8, Canada. [Feldman, Brian M.] Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Publ Hlth Sci, Toronto, ON M5G 1X8, Canada. [Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. [Reed, Ann M.] Mayo Clin, Dept Med, Div Rheumatol, Mayo Coll Med, Rochester, MN USA. [Reed, Ann M.] Mayo Clin, Dept Pediat, Div Rheumatol, Mayo Coll Med, Rochester, MN USA. [Pachman, Lauren M.] Northwestern Univ, Feinberg Sch Med, Childrens Mem Hosp, Dept Pediat,Div Rheumatol, Chicago, IL 60611 USA. [Pachman, Lauren M.] Childrens Mem Res Ctr, Mol & Cellular Pathobiol Program, Chicago, IL USA. RP Feldman, BM (reprint author), Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Pediat, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM brian.feldman@sickkids.ca RI Feldman, Brian/A-8586-2011; OI Rider, Lisa/0000-0002-6912-2458 FU Intramural NIH HHS; NIAMS NIH HHS [R01 AR48289] NR 138 TC 136 Z9 155 U1 1 U2 9 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 JUN-JUL PY 2008 VL 371 IS 9631 BP 2201 EP 2212 DI 10.1016/S0140-6736(08)60955-1 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 326CP UT WOS:000257635800027 PM 18586175 ER PT J AU Grillon, C Alvarez, RP Johnson, L Chavis, C AF Grillon, Christian Alvarez, Ruben P. Johnson, Linda Chavis, Chanen TI Contextual specificity of extinction of delay but not trace eyeblink conditioning in humans SO LEARNING & MEMORY LA English DT Article ID HIPPOCAMPUS; AWARENESS; RABBITS; FEAR AB Renewal of an extinguished conditioned response has been demonstrated in humans and in animals using various types of procedures, except renewal of motor learning such as eyeblink conditioning. We tested renewal of delay and trace eyeblink conditioning in a virtual environment in an ABA design. Following acquisition in one context (A, e. g., an airport) and extinction in a different context (B, e. g., a city), tests for renewal took place in the acquisition (A) and extinction context (B), in a counterbalanced order. Results showed renewal of the extinguished conditioned response in the delay but not trace condition. C1 [Grillon, Christian; Alvarez, Ruben P.; Johnson, Linda; Chavis, Chanen] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. EM christian.grillon@nih.gov FU Intramural NIH HHS [ZIA MH002798-08] NR 14 TC 5 Z9 6 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD JUN PY 2008 VL 15 IS 6 BP 387 EP 389 DI 10.1101/lm.855708 PG 3 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 305VH UT WOS:000256205400001 PM 18509111 ER PT J AU Wang, LM Sun, JG Tong, XW AF Wang, Lianming Sun, Jianguo Tong, Xingwei TI Efficient estimation for the proportional hazards model with bivariate current status data SO LIFETIME DATA ANALYSIS LA English DT Article DE bivariate current status data; efficient estimation; counting processes; sieve method; copula model ID FAILURE TIME DATA; REGRESSION-MODEL; SURVIVAL-DATA; LIFE-TABLES; ASSOCIATION; DISTRIBUTIONS; COPULAS AB We consider efficient estimation of regression and association parameters jointly for bivariate current status data with the marginal proportional hazards model. Current status data occur in many fields including demographical studies and tumorigenicity experiments and several approaches have been proposed for regression analysis of univariate current status data. We discuss bivariate current status data and propose an efficient score estimation approach for the problem. In the approach, the copula model is used for joint survival function with the survival times assumed to follow the proportional hazards model marginally. Simulation studies are performed to evaluate the proposed estimates and suggest that the approach works well in practical situations. A real life data application is provided for illustration. C1 [Wang, Lianming] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Sun, Jianguo] Univ Missouri, Dept Stat, Columbia, MO 65211 USA. [Tong, Xingwei] Beijing Normal Univ, Dept Stat & Financial Math, Beijing 100875, Peoples R China. RP Wang, LM (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM wangl3@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA152035] NR 25 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD JUN PY 2008 VL 14 IS 2 BP 134 EP 153 DI 10.1007/s10985-007-9058-9 PG 20 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 292GX UT WOS:000255255600002 PM 17899375 ER PT J AU Kim, J Horwitz, B AF Kim, Jieun Horwitz, Barry TI Investigating the neural basis for MRI-based functional connectivity in a blocked design: application to interregional correlations and psycho-physiological interactions SO MAGNETIC RESONANCE IMAGING LA English DT Article DE neural modeling; fMRI; brain; hemodynamic response function; deconvolution ID HUMAN BRAIN; FMRI; MULTISUBJECT; MODELS; MEMORY AB This paper investigates how well different kinds of fMRI functional connectivity analysis reflect the underlying interregional neural interactions. This is hard to evaluate using real experimental data where such relationships are unknown. Rather, we use a biologically realistic neural model to simulate both neuronal activities and multiregional fMRI data from a blocked design. Because we know how every element in the model is related to every other element, we can compare functional connectivity measurements across different spatial and temporal scales. We focus on (1) psycho-physiological interaction (PPI) analysis, which is a simple brain connectivity method that characterizes the activity in one brain region by the interaction between another region's activity and a psychological factor, and (2) interregional correlation analysis. We investigated the neurobiological underpinnings of PPI using simulated neural activities and fMRI signals generated by a large-scale neural model that performs a visual delayed match-to-sample task. Simulated fMRI data are generated by convolving integrated synaptic activities (ISAs) with a hemodynamic response function. The simulation was done under three task conditions: high-attention, low-attention and a control task ('passive viewing'). We investigated how biological and scanning parameters affect PPI and compared these with functional connectivity measures obtained using correlation analysis. We performed correlational and PPI analyses with three types of time-series data: ISA, fMRI and deconvolved fMRI (which yields estimated neural signals) obtained using a deconvolution algorithm. The simulated ISA can be considered as the 'gold standard' because it represents the underlying neural activity. Our main findings show (1) that evaluating the change in an interregional functional connection using the difference in regression coefficients (as is essentially done in the PPI method) produces results that better reflect the underlying changes in neural interrelationships than does evaluating the functional connectivity difference as a change in correlation coefficient; (2) that using fMRI and deconvolved fMRI data led to similar conclusions in the PPI-based functional connectivity results, and these generally agreed with the nature of the underlying neural interactions; and (3) the functional connectivity correlation measures often led to different conclusions regarding significance for different scanning and hemodynamic parameters, but the significances of the PPI regression parameters were relatively robust. These results highlight the way in which neural modeling can be used to help validate the inferences one can make about functional connectivity based on fMRI data. Published by Elsevier Inc. C1 [Kim, Jieun; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. EM horwitzb@nidcd.nih.gov FU Intramural NIH HHS NR 23 TC 30 Z9 31 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JUN PY 2008 VL 26 IS 5 BP 583 EP 593 DI 10.1016/j.mri.2007.10.011 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 320ZC UT WOS:000257272700001 PM 18191524 ER PT J AU Zhan, W Jiang, L Loew, MH Yang, YH AF Zhan, Wang Jiang, Li Loew, Murray H. Yang, Yihong TI Mapping spatiotemporal diffusion inside the human brain using a numerical solution of the diffusion equation SO MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion equation; diffusion tensor imaging (DTI); numerical solution; spatiotemporal process ID TENSOR; MRI; ARCHITECTURE; COEFFICIENTS; CANCER; TISSUE; WATER; ECHO AB Diffusion is an important mechanism for molecular transport in living biological tissues. Diffusion magnetic resonance imaging (dMRI) provides a unique probe to examine microscopic structures of the tissues in vivo, but current dMRI techniques usually ignore the spatiotemporal evolution process of the diffusive medium. In the present study, we demonstrate the feasibility to reveal the spatiotemporal diffusion process inside the human brain based on a numerical solution of the diffusion equation. Normal human subjects were scanned with a diffusion tensor imaging (DTI) technique on a 3-T MRI scanner, and the diffusion tenser in each voxel was calculated from the DTI data. The diffusion equation, a partial-derivative description of Fick's law for the diffusion process, was discretized into equivalent algebraic equations. A finite-difference method was employed to obtain the numerical solution of the diffusion equation with a Crank-Nicholson iteration scheme to enhance the numerical stability. By specifying boundary and initial conditions, the spatiotemporal evolution of the diffusion process inside the brain can be virtually reconstructed. Our results exhibit similar medium profiles and diffusion coefficients as those of light fluorescence dextrans measured in integrative optical imaging experiments. The proposed method highlights the feasibility to noninvasively estimate the macroscopic diffusive transport time for a molecule in a given region of the brain. (C) 2008 Elsevier Inc. All rights reserved. C1 [Zhan, Wang; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Zhan, Wang] Univ Calif San Francisco, VA Med Ctr 114M, Dept Radiol, San Francisco, CA 94121 USA. [Jiang, Li; Loew, Murray H.] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. RP Yang, YH (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999, Z01 DA000469-04] NR 32 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JUN PY 2008 VL 26 IS 5 BP 694 EP 702 DI 10.1016/j.mri.2008.01.025 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 320ZC UT WOS:000257272700014 PM 18440744 ER PT J AU Assaf, Y Blumenfeld-Katzir, T Yovel, Y Basser, PJ AF Assaf, Yaniv Blumenfeld-Katzir, Tamar Yovel, Yossi Basser, Peter J. TI AxCaliber: A method for measuring axon diameter distribution from diffusion MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE axon diameter; diffusion; MRI; nerve; q-space ID ANISOTROPIC WATER DIFFUSION; DROPLET SIZE DISTRIBUTIONS; MYELINATED NERVE-FIBERS; HUMAN BRAIN; CONDUCTION-VELOCITY; MAGNETIC-RESONANCE; FIELD GRADIENT; WEIGHTED MRI; WHITE-MATTER; PFG-NMR AB The diameter of a myelinated nerve axon is directly proportional to its conduction velocity, so the axon diameter distribution helps determine the channel capacity of nervous transmission along fascicles in the central (CNS) and peripheral nervous systems (PNS). Previously, this histological information could only be obtained using invasive tissue biopsies. Here we propose a new NMR-based approach that employs a model of water diffusion within "restricted" cylindrical axons to estimate their diameter distribution within a nerve bundle. This approach can be combined with MRI to furnish an estimate of the axon diameter distribution within each voxel. This method is validated by comparing the diameter distributions measured using the NMR and histological techniques on sciatic and optic nerve tissue specimens. The axon diameter distribution measured in each voxel of porcine spinal cord using MRI and using histological methods were similar. Applications are expected in longitudinal studies designed to follow nerve growth in normal and abnormal development, as well as in diagnosing disorders and diseases affecting specific populations of axons in the CNS and PNS. C1 [Assaf, Yaniv; Blumenfeld-Katzir, Tamar; Yovel, Yossi] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. [Basser, Peter J.] NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrated Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Assaf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. EM asafyan@zahav.net.il RI Basser, Peter/H-5477-2011 FU Intramural NIH HHS [Z01 HD000266-10] NR 40 TC 294 Z9 294 U1 2 U2 35 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2008 VL 59 IS 6 BP 1347 EP 1354 DI 10.1002/mrm.21577 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306RV UT WOS:000256266400017 PM 18506799 ER PT J AU Lauretani, F Bandinelli, S Strotmeyer, ES Corsi, AM Di Iorio, A Guralnik, JM Ferrucci, L AF Lauretani, Fulvio Bandinelli, Stefania Strotmeyer, Elsa S. Corsi, Anna Maria Di Iorio, Angelo Guralnik, Jack M. Ferrucci, Luigi TI Erythropoietin and polyneuropathy in older persons SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE EPO; polyneuropathy; prevention; population-based study; InCHIANTI study ID AXONAL DEGENERATION; IN-VITRO; NEUROPROTECTION; EPIDEMIOLOGY; PROTECTS; THERAPY; DECLINE; NEURONS; INJURY; CORD AB Introduction: Recent studies demonstrated that erythropoietin (EPO) have a number of non-erythropoietic effects including neuroprotection and vascular protection. Materials: Using data from a representative sample of older persons, we tested the hypothesis that EPO levels are correlated with peripheral nerve parameters (NVC and CMAP) assessed by surface ENG and with clinically diagnosed polyneuropathy. We selected 972 participants (aged 60-98 years) with complete data for the analyses. Results: We found a significant association between EPO and age-adjusted NCV and CMAP (for NCV: 0.57 +/- 0.26; p = 0.03 and for CMAP: 0.54 +/- 0.23; p = 0.02). In logistic regression models adjusting for age, sex and multiple potential confounders, higher EPO levels were associated with a significantly lower probability of having a clinical diagnosis of polyneuropathy (OR = 0.43; 95% Cl: 0.22-0.84). Discussion: These findings suggest that EPO is implicated in the pathogenesis of polyneuropathy in older persons. Whether low EPO is a risk factor for polyneuropathy should be tested in future longitudinal analyses. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, ASTRA Unit, Baltimore, MD 21225 USA. [Lauretani, Fulvio; Corsi, Anna Maria] Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, Stefania] ASF Florence, Geriatr Unit, Florence, Italy. [Di Iorio, Angelo] Univ G dAnnunzio, Dept Geriatr, Lab Clin Epidemiol Gerontol, Chieti, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog Biometry, Bethesda, MD 20892 USA. [Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, ASTRA Unit, Harbor Hosp 5th Floor,32001 S, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Strotmeyer, Elsa/F-3015-2014; Lauretani, Fulvio/K-5115-2016 OI Strotmeyer, Elsa/0000-0002-4093-6036; Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [ZIA AG001050-08]; NIA NIH HHS [N01-AG-5-0002, N01-AG-821336, N01-AG-916413, R01 AG027012] NR 27 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUN PY 2008 VL 129 IS 6 BP 299 EP 303 DI 10.1016/j.mad.2008.02.006 PG 5 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 315HA UT WOS:000256867900001 PM 18439654 ER PT J AU Duryea, J Magalnick, M Alli, S Yao, L Wilson, M Goldbach-Mansky, R AF Duryea, J. Magalnick, M. Alli, S. Yao, L. Wilson, M. Goldbach-Mansky, R. TI Semiautomated three-dimensional segmentation software to quantify carpal bone volume changes on wrist CT scans for arthritis assessment SO MEDICAL PHYSICS LA English DT Article ID LEVEL SET SEGMENTATION; RHEUMATOID-ARTHRITIS; BREAST-CANCER; IMAGES; ALGORITHM; KNEE; MR AB Rapid progression of joint destruction is an indication of poor prognosis in patients with rheumatoid arthritis. Computed tomography (CT) has the potential to serve as a gold standard for joint imaging since it provides high resolution three-dimensional (3D) images of bone structure. The authors have developed a method to quantify erosion volume changes on wrist CT scans. In this article they present a description and validation of the methodology using multiple scans of a hand phantom and five human subjects. An anthropomorphic hand phantom was imaged with a clinical CT scanner at three different orientations separated by a 30-deg angle. A reader used the semiautomated software tool to segment the individual carpal bones of each CT scan. Reproducibility was measured as the root-mean-square standard deviation (RMMSD) and coefficient of variation (CoV) between multiple measurements of the carpal volumes. Longitudinal erosion progression was studied by inserting simulated erosions in a paired second scan. The change in simulated erosion size was calculated by performing 3D image registration and measuring the volume difference between scans in a region adjacent to the simulated erosion. The RMSSD for the total carpal volumes was 21.0 mm(3) (CoV=1.3%) for the phantom, and 44.1 mm(3) (CoV=3.0%) for the in vivo subjects. Using 3D registration and local volume difference calculations, the RMMSD was 1.0-3.0 mm(3). The reader time was approximately 5 min per carpal bone. There was excellent agreement between the measured and simulated erosion volumes. The effect of a poorly measured volume for a single erosion is mitigated by the large number of subjects that would comprise a clinical study and that there will be many erosions measured per patient. CT promises to be a quantifiable tool to measure erosion volumes and may serve as a gold standard that can be used in the validation of other modalities such as magnetic resonance imaging. (C) 2008 American Association of Physicists in Medicine. C1 [Duryea, J.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. [Magalnick, M.; Alli, S.; Yao, L.; Wilson, M.; Goldbach-Mansky, R.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Duryea, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM jduryea@bwh.harvard.edu FU Intramural NIH HHS NR 20 TC 16 Z9 16 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 JUN PY 2008 VL 35 IS 6 BP 2321 EP 2330 DI 10.1118/1.2900111 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 307FU UT WOS:000256305600021 PM 18649465 ER PT J AU Tromberg, BJ Pogue, BW Paulsen, KD Yodh, AG Boas, DA Cerussi, AE AF Tromberg, Bruce J. Pogue, Brian W. Paulsen, Keith D. Yodh, Arjun G. Boas, David A. Cerussi, Albert E. TI Assessing the future of diffuse optical imaging technologies for breast cancer management SO MEDICAL PHYSICS LA English DT Article ID MONITORING NEOADJUVANT CHEMOTHERAPY; ULTRASOUND LOCALIZATION; FREQUENCY-DOMAIN; MENSTRUAL-CYCLE; TOMOGRAPHY; SPECTROSCOPY; HEMOGLOBIN; MRI; TISSUE; WOMEN AB Diffuse optical imaging (DOI) is a noninvasive optical technique that employs near-infrared (NIR) light to quantitatively characterize the optical properties of thick tissues. Although NIR methods were first applied to breast transillumination (also called diaphanography) nearly 80 years ago, quantitative DOI methods employing time- or frequency-domain photon migration technologies have only recently been used for breast imaging (i.e., since the mid-1990s). In this review, the state of the art in DOI for breast cancer is outlined and a multi-institutional Network for Translational Research in Optical Imaging (NTROI) is described, which has been formed by the National Cancer Institute to advance diffuse optical spectroscopy and imaging (DOSI) for the purpose of improving breast cancer detection and clinical management. DOSI employs broadband technology both in near-infrared spectral and temporal signal domains in order to separate absorption from scattering and quantify uptake of multiple molecular probes based on absorption or fluorescence contrast. Additional dimensionality in the data is provided by integrating and co-registering the functional information of DOSI with x-ray mammography and magnetic resonance imaging (MRI), which provide structural information or vascular flow information, respectively. Factors affecting DOSI performance, such as intrinsic and extrinsic contrast mechanisms, quantitation of biochemical components, image formation/visualization, and multimodality co-registration are under investigation in the ongoing research NTROI sites. One of the goals is to develop standardized DOSI platforms that can be used as stand-alone devices or in conjunction with MRI, mammography, or ultrasound. This broad-based, multidisciplinary effort is expected to provide new insight regarding the origins of breast disease and practical approaches for addressing several key challenges in breast cancer, including: Detecting disease in mammographically dense tissue, distinguishing between malignant and benign lesions, and understanding the impact of neoadjuvant chemotherapies. (c) 2008 American Association of Physicists in Medicine. C1 [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Tromberg, Bruce J.; Yodh, Arjun G.; Boas, David A.; Cerussi, Albert E.] Beckman Laser Inst & Med Clin, NCI Network Translat Res Opt Imaging, Irvine, CA 92612 USA. [Tromberg, Bruce J.; Cerussi, Albert E.] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. [Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. [Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,NMR Ctr, Boston, MA 02129 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P30 CA062203, U54 CA105480, U54 CA105480-010002, U54CA105480]; NCRR NIH HHS [P41 RR001192, P41 RR001192-29] NR 31 TC 169 Z9 172 U1 4 U2 24 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 JUN PY 2008 VL 35 IS 6 BP 2443 EP 2451 DI 10.1118/1.2919078 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 307FU UT WOS:000256305600033 PM 18649477 ER PT J AU Lohman, TG Ring, K Pfeiffer, K Camhi, S Arredondo, E Pratt, C Pate, R Webber, LS AF Lohman, Timothy G. Ring, Kimberly Pfeiffer, Karin Camhi, Sarah Arredondo, Elva Pratt, Charlotte Pate, Russ Webber, Larry S. TI Relationships among fitness, body composition, and physical activity SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE adolescent; fatness; accelerometry; physical fitness; race/ethnicity ID DISEASE RISK-FACTORS; ALL-CAUSE MORTALITY; CARDIORESPIRATORY FITNESS; ADOLESCENT GIRLS; AEROBIC FITNESS; CARDIOVASCULAR FITNESS; ENERGY-EXPENDITURE; CANCER-MORTALITY; JAPANESE MEN; CHILDREN AB Purpose: This study was designed to examine the associations of physical activity and body composition with cardiorespiratory fitness in eighth grade girls. Methods: A random sample of 1440 eighth grade girls at 36 schools participated in this cross-sectional investigation, which represented an ethnically and geographically diverse group. Cardiorespiratory fitness was assessed using a modified physical work capacity test on a cycle ergometer that predicted workload at a heart rate of 170 beats.min(-1). Physical activity was assessed over 6 d in each girl using an accelerometer and body composition was estimated from body mass index and triceps skinfolds using a previously validated equation. Pearson correlations and multiple regression analyses, were used to determine the relationships among fitness, physical activity, and body composition. Results: Significant linear relationships among cardiorespiratory fitness, body composition, and physical activity were found. The combination of fat and fat-free mass along with racial group and a race by fat-free-mass interaction accounted for 18% (R-2) of the variation in physical fitness. Adding moderate-to-vigorous physical activity to the regression model increased the R-2 to 22%. Black girls had somewhat lower fitness levels (P < 0.05) especially at higher levels of fat and fat-free mass than other racial/ethnic groups. Conclusions: Physical activity, fat-free mass, and the interaction between fat-free mass and racial group are significantly associated with cardiorespiratory fitness in adolescent girls. C1 [Lohman, Timothy G.] Univ Arizona, Dept Physiol, Tucson, AZ 85721 USA. [Ring, Kimberly] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Pfeiffer, Karin] Michigan State Univ, Dept Kinesiol, E Lansing, MI 48824 USA. [Camhi, Sarah] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. [Arredondo, Elva] San Diego State Univ, Sch Publ Hlth, San Diego, CA 92182 USA. [Pratt, Charlotte] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Pate, Russ] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. [Webber, Larry S.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA 70118 USA. RP Lohman, TG (reprint author), Univ Arizona, Dept Physiol, 1713 E Univ Blvd 93, Tucson, AZ 85721 USA. EM lohman@u.arizona.edu FU NHLBI NIH HHS [U01 HL066845, U01 HL066853, U01 HL066857, U01HL66858, U01 HL066855, U01 HL066858-06, U01 HL066852, U01 HL066856, U01 HL066858, U01HL66857] NR 38 TC 26 Z9 29 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2008 VL 40 IS 6 BP 1163 EP 1170 DI 10.1249/MSS.0b013e318165c86b PG 8 WC Sport Sciences SC Sport Sciences GA 305DH UT WOS:000256157500024 PM 18460987 ER PT J AU Troiano, RP Berrigan, D AF Troiano, Richard P. Berrigan, David TI Physical activity in the United States measured by accelerometer: Comment - Response SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Letter ID VALIDITY; FIELD C1 [Troiano, Richard P.; Berrigan, David] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Troiano, RP (reprint author), NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2008 VL 40 IS 6 BP 1189 EP 1189 DI 10.1249/MSS.0b013e1817057eb PG 1 WC Sport Sciences SC Sport Sciences GA 305DH UT WOS:000256157500028 ER PT J AU Kim, YS Maruvada, P AF Kim, Young S. Maruvada, Padma TI Frontiers in metabolomics for cancer research: Proceedings of a National Cancer Institute workshop SO METABOLOMICS LA English DT Review DE metabolomics; cancer; prevention; nutrition; technology ID FUNCTIONAL GENOMICS; COLORECTAL-CANCER; ESCHERICHIA-COLI; PYRUVATE-KINASE; CELLS; TOOL; METABONOMICS; PHENOTYPES; OBESITY; TUMORS AB An NCI workshop entitled "Frontiers in Metabolomics for Cancer Research" was held in October 2005 to identify gaps in the application of metabolomics for cancer research and to disseminate information on metabolomics and its potential application. The workshop was sponsored by a number of groups, including the Division of Cancer Prevention, the Division of Cancer Biology, the Division of Cancer Epidemiology and Genetics, and the Center for Cancer Research within the National Cancer Institute, as well as the National Institutes of Health (NIH) Office of Dietary Supplements. Specific aims for the workshop were to (1) identify issues relevant to the use of metabolomics in the measurements of changes in cells or body fluids; (2) review a variety of approaches to metabolite-based phenotyping such as metabolomics arrays and spectroscopic profiles in relation to its application for patients and/or stratification for responders and non-responders to dietary components, drugs, and toxic agents; (3) discuss what additional information metabolomics provides over that given by genomics and/or proteomics; and (4) evaluate the current status of metabolomics technologies as they relate to cancer prevention research. The potential impact of emerging metabolomics technology and research approaches on our understanding of interactions among external environments is obvious. The study of metabolomics, as characterized by the study of small molecular weight compounds, has the promise of discerning subtle changes in metabolic pathways and shifts in mechanistic aspects of homeostasis-within a time span of seconds-that is not possible by other "omic" approaches. Another advantage is that metabolomic research findings are likely to be relevant to a wide range of chronic and/or infectious diseases, including cancer obesity, and cardiovascular disease. This manuscript is a summary of the workshop that highlighted the existing research and literature in the field of metabolomics for cancer research and research recommendations that may provide important steps forward for the future. C1 [Kim, Young S.] NCI, Canc Prevent Div, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. [Maruvada, Padma] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Kim, YS (reprint author), NCI, Canc Prevent Div, Nutr Sci Res Grp, NIH, Execut Plaza N,Room 3156,6130 Execut Blvd, Bethesda, MD 20892 USA. EM yk47s@nih.gov NR 37 TC 5 Z9 6 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD JUN PY 2008 VL 4 IS 2 BP 105 EP 113 DI 10.1007/s11306-008-0109-3 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298IA UT WOS:000255680200001 ER PT J AU Kuo, SR Willingham, MC Bour, SH Andreas, EA Park, SK Jackson, C Duesbery, NS Leppla, SH Tang, WJ Frankel, AE AF Kuo, Shu-Ru Willingham, Mark C. Bour, Sarah H. Andreas, Elissa A. Park, Seong Kyu Jackson, Carney Duesbery, Nicholas S. Leppla, Stephen H. Tang, Wei-Jen Frankel, Arthur E. TI Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage SO MICROBIAL PATHOGENESIS LA English DT Article DE Anthrax lethal toxin; Anthrax edema toxins; Heart failure; Vascular injury ID DIRECTED MONOCLONAL-ANTIBODY; FATAL INHALATIONAL ANTHRAX; LETHAL TOXIN; MODEL; MICE; DYSFUNCTION; INHIBITORS; APOPTOSIS; THERAPY; BINDING AB Bacillus anthracis infections are frequently associated with severe and often irreversible hypotensive shock despite appropriate antibiotics and aggressive hemodynamic and pulmonary support. Based on the observations that the anthrax secreted proteins-protective antigen (PA). lethal factor (LF), and edema factor (EF) also produce shock and mortality in animal models. we chose to characterize further the clinical chemistries and microscopic pathology of toxin treated rats. Groups of three male Sprague Dawley rats received bolus intravenous infusions of PA/LF. PA/EF. LF. or EF alone and blood samples and tissues were collected and assayed for chemistries and tissue pathology. In PA/LF and PA/EF treated animals but not other groups, chemistries showed transaminasemia and elevated lactate dehydrogenase. PA/LF treated animals alone showed elevated hemoglobin and hematocrits: PA/EF treated animals alone showed lymphopenia. Pathology was remarkable for pulmonary edema in PA/LF treated rat lungs,S and pulmonary hemorrhage in PA/EF treated rat lungs. These results are consistent With our and Others' previous findings that the morbidity and mortality associated with anthrax are not cytokine-mediated but due to a direct effect of the toxins on the cardiovascular system along with toxin-specific alterations in blood counts. PA/LF pathology matches that seen With acute cardiac failure, and PA/EF pathology coincides with direct vascular endothelial injury. These observations provide a rational basis for drug interventions 10 reduce the effect of these toxins on the heart and blood vessels. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Kuo, Shu-Ru; Bour, Sarah H.; Andreas, Elissa A.; Park, Seong Kyu; Frankel, Arthur E.] Scott & White Mem Hosp & Clin, Canc Res Inst, Sherwood & Brindley Fdn, Temple, TX 76502 USA. [Willingham, Mark C.] Wake Forest Univ, Dept Pathol, Tumor Biol Sect, Winston Salem, NC 27109 USA. [Jackson, Carney] Univ Kentucky, Livestock Dis Diagnost Ctr, Sch Vet Med, Lexington, KY USA. [Duesbery, Nicholas S.] Van Andel Res Inst, Grand Rapids, MI USA. [Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, Bethesda, MD 20892 USA. [Tang, Wei-Jen] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. RP Frankel, AE (reprint author), Scott & White Mem Hosp & Clin, Canc Res Inst, Sherwood & Brindley Fdn, 5701 S Airport Rd, Temple, TX 76502 USA. EM afrankel@swmail.sw.org OI Tang, Wei-Jen/0000-0002-8267-8995; DUESBERY, NICK/0000-0002-4258-5655 NR 26 TC 37 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JUN PY 2008 VL 44 IS 6 BP 467 EP 472 DI 10.1016/j.micpath.2007.12.001 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA 396KS UT WOS:000262591200002 PM 18222626 ER PT J AU Gnanasekar, M Anandharaman, V Anand, SB Nutman, TB Ramaswamy, K AF Gnanasekar, Munirathinam Anandharaman, Veerapathran Anand, Setty Balakrishnan Nutman, Thomas B. Ramaswamy, Kalyanasundaram TI A novel small heat shock protein 12.6 (HSP12.6) from Brugia malayi functions as a human IL-10 receptor binding protein SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Brugia malayi; HSP12.6; IL-10; phage display; biopanning ID HEAT-SHOCK PROTEINS; LYMPHATIC FILARIASIS; NEMATODE PARASITES; HELMINTH-PARASITES; ALPHA-CRYSTALLIN; IMMUNE EVASION; EXPRESSION; THERMOTOLERANCE; INTERLEUKIN-10; INFECTION AB Phage display cDNA expression library of the third stage larvae (L3) of Brugia malayi was screened for identifying target(s) that bound to the human interleukin-10 receptor (huIL10R). This iterative screening identified an insert that showed significant homology to Caenorhabditis elegans HSP12.6. The gene was designated B. malayi HSP12.6 (BmHSP12.6) and has orthologues in several gastrointestinal nematode genome (Ancylostoma caninum, Ascarls lumbricoides and Ascaris suum) but the gene or gene product has not been studied further in these parasites. Structural analyses of BmHSP12.6 showed that it has a highly conserved alpha-crystallin central domain that is characteristic of other small heat shock proteins (HSPs). BmHSP12.6 has a short N-terminal domain and an unusually small C-terminal domain flanking the crystallin domain suggesting that this protein belongs to a novel class of small HSPs. BmHSP12.6 appears to be differentially transcribed with highest expression in the vertebrate stages of the parasite (L4, adult and mf) compared to its mosquito vector stage (L3). More importantly recombinant BmHSP12.6 bound to huIL10R in a dose dependent fashion and inhibited the binding of human IL-10 (huIL10) to huIL10R in vitro. rBmHSP12.6 also enhanced the growth and proliferation of MC/9 mast cells in vitro similar to huIL10. This study thus describes a novel small HSP from B. malayi that has the capacity to bind to huIL10R, block binding of huIL10 to huIL10R and function similar to huIL10. (c) 2008 Elsevier B.V. All rights reserved. C1 [Gnanasekar, Munirathinam; Anandharaman, Veerapathran; Anand, Setty Balakrishnan; Ramaswamy, Kalyanasundaram] Univ Illinois, Coll Med, Dept Biomed Sci, Rockford, IL 61107 USA. [Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Ramaswamy, K (reprint author), Univ Illinois, Coll Med, Dept Biomed Sci, 1601 Parkview Ave, Rockford, IL 61107 USA. EM ramswamy@uic.edu FU NIAID NIH HHS [R56 AI064745, R01 AI064745, R56 AI064745-01A1, R01 AI064745-01A2, AI 064745] NR 28 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 2008 VL 159 IS 2 BP 98 EP 103 DI 10.1016/j.molbiopara.2008.02.010 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 305SL UT WOS:000256198000003 PM 18395809 ER PT J AU Ohguchi, H Tanaka, T Uchida, A Magoori, K Kudo, H Kim, I Daigo, K Sakakibara, I Okamura, M Harigae, H Sasaki, T Osborne, TF Gonzalez, FJ Hamakubo, T Kodama, T Sakai, J AF Ohguchi, Hiroto Tanaka, Toshiya Uchida, Aoi Magoori, Kenta Kudo, Hiromi Kim, Insook Daigo, Kenji Sakakibara, Iori Okamura, Masashi Harigae, Hideo Sasaki, Takeshi Osborne, Timothy F. Gonzalez, Frank J. Hamakubo, Takao Kodama, Tatsuhiko Sakai, Juro TI Hepatocyte nuclear factor 4 alpha contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Kruppel-like transcription factor 9 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELEMENT-BINDING PROTEINS; ZINC-FINGER PROTEIN; FACTOR 4-ALPHA; ADIPOCYTE DIFFERENTIATION; RECEPTOR SUPERFAMILY; TARGETED DISRUPTION; FUNCTIONAL DOMAINS; DEVELOPING HEART; DIO1 GENE; IN-VIVO AB Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Diol mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4 alpha (HNF4 alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T(4) and rT(3) concentrations are elevated in these mice compared with those in HNF4 alpha-floxed control littermates; however, serum T(3) levels are unchanged. Promoter analysis of the mouse Diol gene demonstrated that HNF4 alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4 alpha site (direct repeat 1 [TGGACAAA GGTGC]; HNF4 alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4 alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone- inducible Kruppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4 alpha-RE. Furthermore, KLF9 functions together with HNF4 alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4 alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4 alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9. C1 [Ohguchi, Hiroto; Tanaka, Toshiya; Uchida, Aoi; Magoori, Kenta; Kudo, Hiromi; Daigo, Kenji; Sakakibara, Iori; Okamura, Masashi; Hamakubo, Takao; Kodama, Tatsuhiko; Sakai, Juro] Univ Tokyo, Adv Sci & Technol Res Ctr, Lab Syst Biol & Med, Meguro Ku, Tokyo 1538904, Japan. [Ohguchi, Hiroto; Harigae, Hideo; Sasaki, Takeshi] Tohoku Univ, Grad Sch Med, Dept Hematol & Rheumatol, Aoba Ku, Sendai, Miyagi 9808574, Japan. [Kim, Insook; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Osborne, Timothy F.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. RP Sakai, J (reprint author), Univ Tokyo, Adv Sci & Technol Res Ctr, Lab Syst Biol & Med, Meguro Ku, 4-6-1 Komaba, Tokyo 1538904, Japan. EM jmsakai-tky@umin.ac.jp RI Daigo, Kenji/S-8915-2016 OI Daigo, Kenji/0000-0001-6398-3356 NR 70 TC 25 Z9 26 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2008 VL 28 IS 12 BP 3917 EP 3931 DI 10.1128/MCB.02154-07 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309HT UT WOS:000256452000004 PM 18426912 ER PT J AU Wu, YL Shin-ya, K Brosh, RM AF Wu, Yuliang Shin-ya, Kazuo Brosh, Robert M., Jr. TI FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SISTER-CHROMATID COHESION; REPLICATION PROTEIN-A; CROSS-LINK REPAIR; HUMAN TUMOR-CELLS; CAENORHABDITIS-ELEGANS; HOMOLOGOUS RECOMBINATION; SUBSTRATE-SPECIFICITY; TELOMERASE INHIBITOR; BACH1; TELOMESTATIN AB FANCJ mutations are associated with breast cancer and genetically linked to the bone marrow disease Fanconi anemia (FA). The genomic instability of FA-J mutant cells suggests that FANCJ helicase functions in the replicational stress response. A putative helicase with sequence similarity to FANCJ in Caenorhabditis elegans (DOG-1) and mouse (RTEL) is required for poly(G) tract maintenance, suggesting its involvement in the resolution of alternate DNA structures that impede replication. Under physiological conditions, guanine-rich sequences spontaneously assemble into four-stranded structures (G quadruplexes [G4]) that influence genomic stability. FANCJ unwound G4 DNA substrates in an ATPase-dependent manner. FANCJ G4 unwinding is specific since another superfamily 2 helicase, RECQ1, failed to unwind all G4 substrates tested under conditions in which the helicase unwound duplex DNA. Replication protein A stimulated FANCJ G4 unwinding, whereas the mismatch repair complex MSH2/MSH6 inhibited this activity. FANCJ-depleted cells treated with the G4-interactive compound telomestatin displayed impaired proliferation and elevated levels of apoptosis and DNA damage compared to small interfering RNA control cells, suggesting that G4 DNA is a physiological substrate of FANCJ. Although the FA pathway has been classically described in terms of interstrand cross-link (ICL) repair, the cellular defects associated with FANCJ mutation extend beyond the reduced ability to repair ICLs and involve other types of DNA structural roadblocks to replication. C1 [Wu, Yuliang; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Shin-ya, Kazuo] Natl Inst Adv Ind Sci & Technol, Tokyo 1350064, Japan. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov FU Intramural NIH HHS NR 49 TC 176 Z9 182 U1 1 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2008 VL 28 IS 12 BP 4116 EP 4128 DI 10.1128/MCB.02210-07 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309HT UT WOS:000256452000020 PM 18426915 ER PT J AU Roy, SW Irimia, M AF Roy, Scott William Irimia, Manuel TI Origins of human malaria: Rare genomic changes and full mitochondrial genomes confirm the relationship of Plasmodium falciparum to other mammalian parasites but complicate the origins of Plasmodium vivax SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE apicomplexan evolution; phylogenetic methods; rare genomic characters; parasite evolution ID SUBUNIT RIBOSOMAL-RNA; INTRON CONSERVATION; GENE-SEQUENCES; SPLICEOSOMAL INTRONS; CYTOCHROME-B; EVOLUTION; PATTERN; LOSS/GAIN; PHYLOGENY; COELOMATA AB Despite substantial work, the phylogeny of malaria parasites remains debated. The matter is complicated by concerns about patterns of evolution in potentially strongly selected genes as well as the extreme AT bias of some Plasmodium genomes. Particularly contentious has been the position of the most virulent human parasite Plasmodium falciparum, whether grouped with avian parasites or within a larger clade of mammalian parasites. Here, we study 3 classes of rare genomic changes, as well as the sequences of mitochondrial ribosomal RNA (rRNA) genes. We report 3 lines of support for a clade of mammalian parasites: 1) we find no instances of spliceosomal intron loss in a hypothetical ancestor of P. falciparum and the avian parasite Plasmodium gallinaceum, suggesting against a close relationship between those species; 2) we find 4 genomic mitochondrial indels supporting a mammalian clade, but none grouping P. falciparum with avian parasites; and 3) slowly evolving mitochondrial rRNA sequences support a mammalian parasite clade with 100% posterior probability. We further report a large deletion in the mitochondrial large subunit rRNA gene, which suggests a subclade including both African and Asian parasites within the clade of closely related primate malarias. This contrasts with previous studies that provided strong support for separate Asian and African clades, and reduces certainty about the historical and geographic origins of Plasmodium vivax. Finally, we find a lack of synapomorphic gene losses, suggesting a low rate of ancestral gene loss in Plasmodium. C1 [Roy, Scott William] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Irimia, Manuel] Univ Barcelona, Fac Biol, Dept Genet, Barcelona, Spain. RP Roy, SW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM scottwroy@gmail.com RI Irimia, Manuel/E-3040-2010; OI Irimia, Manuel/0000-0002-2179-2567 FU Intramural NIH HHS NR 33 TC 17 Z9 18 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUN PY 2008 VL 25 IS 6 BP 1192 EP 1198 DI 10.1093/molbev/msn069 PG 7 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 299LX UT WOS:000255758200019 PM 18359945 ER PT J AU Joy, DA Gonzalez-Ceron, L Carlton, JM Gueye, A Fay, M McCutchan, TF Su, XZ AF Joy, Deirdre A. Gonzalez-Ceron, Lilia Carlton, Jane M. Gueye, Amy Fay, Michael McCutchan, Thomas F. Su, Xin-zhuan TI Local adaptation and vector-mediated population structure in Plasmodium vivax malaria SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE malaria; Plasmodium vivax; microsatellites; coevolution ID ANOPHELES-ALBIMANUS POPULATIONS; MULTILOCUS GENOTYPE DATA; GENETIC-STRUCTURE; SOUTH-AMERICA; MITOCHONDRIAL-DNA; SELECTIVE SWEEPS; GAMBIAE SL; FALCIPARUM; PSEUDOPUNCTIPENNIS; COEVOLUTION AB Plasmodium vivax in southern Mexico exhibits different infectivities to 2 local mosquito vectors, Anopheles pseudopunctipennis and Anopheles albimanus. Previous work has tied these differences in mosquito infectivity to variation in the central repeat motif of the malaria parasite's circumsporozoite (csp) gene, but subsequent studies have questioned this view. Here we present evidence that P. vivax in southern Mexico comprised 3 genetic populations whose distributions largely mirror those of the 2 mosquito vectors. Additionally, laboratory colony feeding experiments indicate that parasite populations are most compatible with sympatric mosquito species. Our results suggest that reciprocal selection between malaria parasites and mosquito vectors has led to local adaptation of the parasite. Adaptation to local vectors may play an important role in generating population structure in Plasmodium. A better understanding of coevolutionary dynamics between sympatric mosquitoes and parasites will facilitate the identification of molecular mechanisms relevant to disease transmission in nature and provide crucial information for malaria control. C1 [Joy, Deirdre A.; McCutchan, Thomas F.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Gonzalez-Ceron, Lilia] Inst Nacl Salud Publ, Chiapas, Chiapas State, Mexico. [Carlton, Jane M.] NYU, Sch Med, Dept Med Parasitol, New York, NY 10003 USA. [Fay, Michael] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Joy, DA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM djoy@mail.nih.gov RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS NR 62 TC 64 Z9 65 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUN PY 2008 VL 25 IS 6 BP 1245 EP 1252 DI 10.1093/molbev/msn073 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 299LX UT WOS:000255758200025 PM 18385220 ER PT J AU Perez-Victoria, FJ Mardones, GA Bonifacino, JS AF Perez-Victoria, F. Javier Mardones, Gonzalo A. Bonifacino, Juan S. TI Requirement of the human GARP complex for mannose 6-phosphate-receptor-dependent sorting of cathepsin D to lysosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TRANS-GOLGI NETWORK; TO-TGN TRANSPORT; EFFICIENT RETROGRADE TRANSPORT; SHIGA-TOXIN; 6-PHOSPHATE RECEPTOR; EARLY ENDOSOME; SNARE TLG1P; WOBBLER MOUSE; GGA PROTEINS; RETROMER AB The biosynthetic sorting of acid hydrolases to lysosomes relies on transmembrane, mannose 6-phosphate receptors (MPRs) that cycle between the TGN and endosomes. Herein we report that maintenance of this cycling requires the function of the mammalian Golgi-associated retrograde protein (GARP) complex. Depletion of any of the three GARP subunits, Vps52, Vps53, or Vps54, by RNAi impairs sorting of the precursor of the acid hydrolase, cathepsin D, to lysosomes and leads to its secretion into the culture medium. As a consequence, lysosomes become swollen, likely due to a buildup of undegraded materials. Missorting of cathepsin D in GARP-depleted cells results from accumulation of recycling MPRs in a population of light, small vesicles downstream of endosomes. These vesicles might correspond to intermediates in retrograde transport from endosomes to the TGN. Depletion of GARP subunits also blocks the retrograde transport of the TGN protein, TGN46, and the B subunit of Shiga toxin. These observations indicate that the mammalian GARP complex plays a general role in the delivery of retrograde cargo into the TGN. We also report that a Vps54 mutant protein in the Wobbler mouse strain is active in retrograde transport, thus explaining the viability of these mutant mice. C1 [Perez-Victoria, F. Javier; Mardones, Gonzalo A.; Bonifacino, Juan S.] NICHHD, Cell Biol & Metab Program, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Program, Natl Inst Hlth, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural Program of National Institute of Child Health and Human Development; National Institutes of Health; Ministerio de Educacion y Ciencia of Spain FX We thank X. Zhu and H.-I. Tsai for expert technical assistance, L. Johannes for Cy3-STxB, M. Marks (University of Pennsylvania, Philadelphia, PA) for antibody to p230, and J. G. Magadan for critical review of the manuscript. This work was funded by the Intramural Program of National Institute of Child Health and Human Development, National Institutes of Health. F. J. P-V. is the recipient of a postdoctoral fellowship from the Ministerio de Educacion y Ciencia of Spain. NR 48 TC 76 Z9 80 U1 0 U2 6 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 JUN PY 2008 VL 19 IS 6 BP 2350 EP 2362 DI 10.1091/mbc.E07-11-1189 PG 13 WC Cell Biology SC Cell Biology GA 347QD UT WOS:000259155200001 PM 18367545 ER PT J AU Jaluria, P Chu, C Betenbaugh, M Shiloach, J AF Jaluria, Pratik Chu, Chia Betenbaugh, Michael Shiloach, Joseph TI Cells by design: A mini-review of targeting cell engineering using DNA microarrays SO MOLECULAR BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT Conference on Protein Expression in Animal Cells CY SEP 16-20, 2007 CL Angra dos Reis, BRAZIL DE microarrays; cellular properties; adhesion; growth; adaptation; cell engineering ID SERUM-FREE MEDIA; ESCHERICHIA-COLI; CORYNEBACTERIUM-GLUTAMICUM; MAMMALIAN-CELLS; CULTURE; GENE; APOPTOSIS; GROWTH; ADAPTATION; LYSINE AB Recent studies have demonstrated the utility of DNA microarray technology in engineering cellular properties. For instance, cellular adhesion, the necessity of cells to attach to a surface in order to to proliferate, was examined by comparing two distinct HeLa cell lines. Two genes, one encoding a type II membrane glycosylating sialyltransferase (siat7e) and the other encoding a secreted glycoprotein (lama4), were found to influence adhesion. The expression of siat7e correlated with reduced adhesion, whereas expression of lama4 correlated with increased adhesion, as shown by various assays. In a separate example, a gene encoding a mitochondrial assembly protein (cox15) and a gene encoding a kinase (cdkl3), were found to influence cellular growth. Enhanced expression of either gene resulted in slightly higher specific growth rates and higher maximum cell densities for HeLa, HEK-293, and CHO cell lines. Another investigated property was the adaptation of HEK-293 cells to serum-free media. The genes egr1 and gas6, both with anti-apoptotic properties, were identified as potentially improving adaptability by impacting viability at low serum levels. In trying to control apoptosis, researchers found that by altering the expression levels of four genes faim, fadd, alg-2, and requiem, apoptotic response could be altered. In the present work, these and related studies in microorganisms (prokaryote and eukaryote) are examined in greater detail focusing on the approach of using DNA microarrays to direct cellular behavior by targeting select genes. C1 [Jaluria, Pratik; Chu, Chia; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Jaluria, Pratik; Chu, Chia; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A Room 173, Bethesda, MD 20892 USA. EM yossi@nih.gov RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 FU Intramural NIH HHS NR 30 TC 10 Z9 11 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JUN PY 2008 VL 39 IS 2 BP 105 EP 111 DI 10.1007/s12033-008-9048-5 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 304BY UT WOS:000256086200004 PM 18327555 ER PT J AU Ikediobi, ON Reimers, M Durinck, S Blower, PE Futreal, AP Stratton, MR Weinstein, JN AF Ikediobi, Ogechi N. Reimers, Mark Durinck, Steffen Blower, Paul E. Futreal, Andrew P. Stratton, Michael R. Weinstein, John N. TI In vitro differential sensitivity c phenothiazines is based on the codon 600 BRAF mutation SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CANCER-CELL-LINES; ANTICANCER DRUG SCREEN; GENE-EXPRESSION; MOLECULAR PHARMACOLOGY; TUMOR-CELLS; B-RAF; RESISTANCE; PTEN; GEFITINIB; DISCOVERY AB The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. We previously sequenced 24 cancer genes in those cell lines. Eleven of the genes were found to be mutated in three or more of the lines. Using a pharmacogenomic approach, we analyzed the relationship between drug activity and mutations in those 11 genes (APC, RB1, KRAS, NRAS, BRAF, PIK3CA, PTEN, STK11, MADH4, TP53, and CDKN2A). That analysis identified an association between mutation in BRAF and the antiproliferative potential of phenothiazine compounds. Phenothiazines have been used as antipsychotics and as adjunct antiemetics during cancer chemotherapy and more recently have been reported to have anticancer properties. However, to date, the anticancer mechanism of action of phenothiazines has not been elucidated. To follow up on the initial pharmacologic observations in the NCI-60 screen, we did pharmacologic experiments on 11 of the NCI-60 cell lines and, prospectively, on an additional 24 lines. The studies provide evidence that BRAF mutation (codon 600) in melanoma as opposed to RAS mutation is predictive of an increase in sensitivity to phenothiazines as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay (Wilcoxon P = 0.007). That pattern of increased sensitivity to phenothiazines based on the presence of codon 600 BRAF mutation may be unique to melanomas, as we do not observe it in a panel of colorectal cancers. The findings reported here have potential implications for the use of phenothiazines in the treatment of V600E BRAF mutant melanoma. C1 [Ikediobi, Ogechi N.] Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, San Francisco, CA 94118 USA. [Ikediobi, Ogechi N.; Reimers, Mark; Weinstein, John N.] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Ikediobi, Ogechi N.; Futreal, Andrew P.; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. [Durinck, Steffen] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Blower, Paul E.] Ohio State Univ, Dept Pharmacol, Program Pharmacogenom, Columbus, OH 43210 USA. [Blower, Paul E.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Ikediobi, ON (reprint author), Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, 3333 Calif St,Box 0613, San Francisco, CA 94118 USA. EM ikediobio@pharmacy.ucsf.edu FU Intramural NIH HHS; Wellcome Trust [077012] NR 45 TC 6 Z9 6 U1 0 U2 1 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 JUN PY 2008 VL 7 IS 6 BP 1337 EP 1346 DI 10.1158/1535-7163.MCT-07-2308 PG 10 WC Oncology SC Oncology GA 316NF UT WOS:000256955900001 PM 18524847 ER PT J AU LaVallee, TM Burke, PA Swartz, GM Hamel, E Agoston, GE Shah, J Suwandi, L Hanson, AD Fogler, WE Sidor, CF Treston, AM AF LaVallee, Theresa M. Burke, Patricia A. Swartz, Glenn M. Hamel, Ernest Agoston, Gregory E. Shah, Jamshed Suwandi, Lita Hanson, Art D. Fogler, William E. Sidor, Carolyn F. Treston, Anthony M. TI Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID INHIBITS TUBULIN POLYMERIZATION; ENDOGENOUS MAMMALIAN METABOLITE; PHASE-I; SOLID TUMORS; 2-METHOXYESTRADIOL ANALOGS; ORAL 2-METHOXYESTRADIOL; ANTIMITOTIC ACTIVITY; CANCER-THERAPY; BREAST-CANCER; ANGIOGENESIS AB Clinical studies using the microtubule-targeting agent 2-methoxyestradiol (2ME2; Panzem) in cancer patients show that treatment is associated with clinical benefit, including prolonged stable disease, complete and partial responses, and an excellent safety profile. Studies have shown that 2ME2 is metabolized by conjugation at positions 3 and 17 and oxidation at position 17. To define structure-activity relationships for these positions of 2ME2 and to generate metabolically stable analogues with improved anti-tubulin properties, a series of analogues was generated and three lead analogues were selected, ENMD-1198, ENMD-1200, and ENMD-1237. These molecules showed improved metabolic stability with > 65% remaining after 2-h incubation with hepatocytes. Pharmacokinetic studies showed that oral administration of the compounds resulted in increased plasma levels compared with 2ME2. All three analogues bind the colchicine binding site of tubulin, induce G(2)-M cell cycle arrest and apoptosis, and reduce hypoxia-inducible factor-1 alpha levels. ENMD-1198 and ENMD-1200 showed improved in vitro antiproliferative activities. Significant reductions in tumor volumes compared with vehicle-treated mice were observed in an orthotopic breast carcinoma (MDA-MB-231) xenograft model following daily oral treatment with all compounds (ANOVA, P < 0.05). Significantly improved median survival time was observed with ENMD-1198 and ENMD-1237 (200 mg/kg/d) in a Lewis lung carcinoma metastatic model (P < 0.05). In both tumor models, the high-dose group of ENMD-1198 showed antitumor activity equivalent to that of cyclophosphamide. ENMD-1198 was selected as the lead molecule in this analogue series and is currently in a phase I clinical trial in patients with refractory solid tumors. C1 [LaVallee, Theresa M.; Burke, Patricia A.; Swartz, Glenn M.; Agoston, Gregory E.; Shah, Jamshed; Suwandi, Lita; Hanson, Art D.; Fogler, William E.; Sidor, Carolyn F.; Treston, Anthony M.] EntreMed Inc, Rockville, MD USA. [Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA. RP Treston, AM (reprint author), 9640 Med Ctr Dr, Rockville, MD 20850 USA. EM tonyt@entremed.com NR 40 TC 49 Z9 53 U1 0 U2 5 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 JUN PY 2008 VL 7 IS 6 BP 1472 EP 1482 DI 10.1158/1535-7163.MCT-08-0107 PG 11 WC Oncology SC Oncology GA 316NF UT WOS:000256955900014 PM 18566218 ER PT J AU Kioi, M Seetharam, S Puri, RK AF Kioi, Mitomu Seetharam, Saraswathy Puri, Rai K. TI Targeting IL-13R alpha 2-positive cancer with a novel recombinant immunotoxin composed of a single-chain antibody and mutated Pseudomonas exotoxin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RECEPTOR ALPHA-2 CHAIN; T-CELL LYMPHOMA; INTERLEUKIN-13 RECEPTOR; MALIGNANT GLIOMA; DENILEUKIN DIFTITOX; CYTOTOXIN; THERAPY; ANTAGONIST; DELIVERY; PROTEIN AB We have shown previously that high-affinity receptors for interleukin-13 (IL-11R alpha 2) are overexpressed on a variety of solid cancer cells, diseased fibroblasts, and other cells, and a chimeric fusion protein composed of human IL-13 and mutated Pseudomonas exotoxin (IL-13-PE38) is highly and specifically cytotoxic to these cells in vitro and in vivo. To improve the specificity for the target, we isolated specific antibodies against IL-13R alpha 2 from human single-chain Fv (scFv) antibody phage library and developed immunotoxin by selecting two high-affinity clones of scFv and fused to PE. The fusion chimeric gene was expressed in Escherichia coli, and highly purified IL-13R-specific immunotoxin, termed anti-IL-13R alpha 2(scFv)-PE38, was tested for its cytotoxicity. This molecule was highly cytotoxic to U251 glioma and PM-RCC renal cell carcinoma cell lines in vitro. The cytotoxic activity was neutralized by purified extracellular domain of IL-13R alpha 2 but not by IL-13, indicating that cytotoxic activity is specific. Anti-IL-13R alpha 2(scFv)-PE38 showed significant antitumor activity in immuno-deficient mice with s.c. glioma tumors. Both i.p. and i.t. routes of administration showed antitumor activity in a dose-dependent manner. The maximum tolerated dose of anti-IL-13R alpha 2(scFv)-PE38 was 200 mu g/kg i.p. twice daily for 5 days. These results indicate that anti-IL13R alpha 2(scFv)-PE38 is a highly selective therapeutic agent for cancer therapy and should be further tested in animal models of human cancer. C1 [Kioi, Mitomu; Seetharam, Saraswathy; Puri, Rai K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 27 TC 40 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2008 VL 7 IS 6 BP 1579 EP 1587 DI 10.1158/1535-7163.MCT-07-2131 PG 9 WC Oncology SC Oncology GA 316NF UT WOS:000256955900025 PM 18566228 ER PT J AU Liao, MJ Zhang, Y Dufau, ML AF Liao, Mingjuan Zhang, Ying Dufau, Maria L. TI Protein kinase C alpha-induced derepression of the human luteinizing hormone receptor gene transcription through ERK-mediated release of HDAC1/Sin3A repressor complex from Sp1 sites SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; REGULATE TRANSCRIPTION; DNA-BINDING; PKC-ALPHA; ACTIVATION; PHOSPHORYLATION; PROMOTER; EXPRESSION; CELLS; GNRH AB LH receptor (LHR) gene transcription is subject to repression/derepression through various modes and multiple effectors. Epigenetic silencing and activation of the LHR is achieved through coordinated regulation at both histone and DNA levels. The LHR gene is subject to repression by deacetylation and methylation at its promoter region, where a HDAC/mSin3A repressor complex is anchored at Sp1 sites. The present studies revealed that protein kinase C (PKC) alpha/ERK signaling is important for the activation of LHR promoter activity, and the increase of endogenous transcripts induced by phorbol-12-myristate-13-acetate (PMA) in HeLa cells. Whereas these effects were attributable to PKC alpha activity, the ERK pathway was the downstream effector in LHR activation. PMA caused a significant enhancement of Sp1 phosphorylation at serine residue (s), which was blocked by PKC alpha or ERK inhibition. The interaction of activated phosphorylated ERK with Sp1 and ERK's association with the LHR promoter points to Sp1 as a direct target of ERK. After Sp1 phosphorylation, the HDAC1/mSin3A repressor complex dissociated from Sp1 sites, histone 3 was acetylated, and transcription factor II B and RNA polymerase II were recruited. In addition, overexpression of a constitutively active PKC alpha (PKC alpha CA) strongly activated LHR transcription in MCF-7 cells ( devoid of PKC alpha), induced Sp1 phosphorylation at serine residue (s) and caused derecruitment of HDAC1/mSin3A complex from the promoter. These effects were negated by cotransfection of a dominant-negative PKC alpha), In conclusion, these studies have revealed a novel regulatory signaling mechanism of transcriptional control in which the LHR is derepressed through PKC alpha/ERK-mediated Sp1 phosphorylation, causing the release of HDAC1/mSin3A complex from the promoter. C1 [Liao, Mingjuan; Zhang, Ying; Dufau, Maria L.] NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bldg 49,Room 6A-36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov FU Intramural NIH HHS NR 68 TC 27 Z9 27 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2008 VL 22 IS 6 BP 1449 EP 1463 DI 10.1210/me.2008-0035 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 307GQ UT WOS:000256307800015 PM 18372343 ER PT J AU Westbroek, W Tuchman, M Tinloy, B De Wever, O Vilboux, T Hertz, JM Hasle, H Heilmann, C Helip-Wooley, A Kleta, R Gahl, WA AF Westbroek, Wendy Tuchman, Maya Tinloy, Bradford De Wever, Olivier Vilboux, Thierry Hertz, Jens M. Hasle, Henrik Heilmann, Carsten Helip-Wooley, Amanda Kleta, Robert Gahl, William A. TI A novel missense mutation (G43S) in the switch I region of Rab27A causing Griscelli syndrome SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Griscelli syndrome; Rab27A; melanosome; Melanophilin; Myosin Va; switch I region ID MYOSIN-VA; MELANOSOME TRANSPORT; PURKINJE-CELLS; NEUROLOGICAL INVOLVEMENT; HUMAN MELANOCYTES; LINKER PROTEIN; ORGANELLE; MICE; SLAC2-A/MELANOPHILIN; DEFECTS AB The autosomal recessive Griscelli syndrome type II (GSII) is caused by mutations in the RAB27A gene. Typical clinical features include immunological impairment, silver-gray scalp hair, eyelashes and eyebrows and hypomelanosis of the skin. Rabs help determine the specificity of membrane trafficking steps within cells. In melanocytes, the GTP-bound form of Rab27A associates with the membranes of mature fully-pigmented melanosomes through its geranylgeranyl group. Once attached, Rab27A recruits the downstream effector Melanophilin (Mlph) and the actin-dependent motor protein Myosin Va (MyoVa). The molecular Rab27A/Mlph/MyoVA tripartite complex, which links melanosomes to the peripheral actin network, is required to achieve melanosome transfer to surrounding keratinocytes in the epidermis. Here we report a novel homozygous missense mutation c.127G>A, p.G43S in exon 2 of the RAB27A gene of an Afghani GSII patient. Laser scanning confocal microscopy showed that the G43S mutation, which is located in the highly conserved switch I region of Rab27A, induces perinuclear localization of melanosomes in normal melanocytes, and fails to restore melanosomes to the actin-rich periphery in GSII melanocytes. Co-immunoprecipitation studies showed that Rab27A(G43S) fails to interact with its effector Melanophilin, indicating that the switch I region functions in the recruitment of Rab effector proteins. (c) 2008 Elsevier Inc. All rights reserved. C1 [Westbroek, Wendy; Tuchman, Maya; Tinloy, Bradford; Vilboux, Thierry; Helip-Wooley, Amanda; Kleta, Robert; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, Bethesda, MD 20892 USA. [De Wever, Olivier] State Univ Ghent Hosp, Lab Expt Canc Res, Ghent, Belgium. [Hertz, Jens M.] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Hasle, Henrik] Aarhus Univ Hosp, Dept Pediat, DK-8000 Aarhus, Denmark. [Heilmann, Carsten] Rigshosp, Pediat Clin 2, DK-2100 Copenhagen, Denmark. RP Westbroek, W (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, Bldg 10,Room 10C-107,MSC 1851,10 Ctr Dr, Bethesda, MD 20892 USA. EM wwestbro@mail.nih.gov RI de wever, olivier/J-3094-2013; Hertz, Jens Michael/H-6269-2014; OI de wever, olivier/0000-0002-5453-760X; Hasle, Henrik/0000-0003-3976-9231 FU Intramural NIH HHS [Z99 HG999999] NR 41 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2008 VL 94 IS 2 BP 248 EP 254 DI 10.1016/j.ymgme.2008.02.009 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 308EU UT WOS:000256371900015 PM 18397837 ER PT J AU Hurt, EM Farrar, WL AF Hurt, Elaine M. Farrar, William L. TI Cancer Stem Cells: The Seeds of Metastasis? SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID BREAST-CANCER; PANCREATIC-CANCER; IDENTIFICATION; TUMORS C1 [Hurt, Elaine M.; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Hurt, EM (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov; hurte@ncifcrf.gov FU Intramural NIH HHS NR 20 TC 20 Z9 23 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD JUN 1 PY 2008 VL 8 IS 3 BP 140 EP 142 DI 10.1124/mi.8.3.7 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366IE UT WOS:000260473300006 PM 18693193 ER PT J AU Edgar, R Rokney, A Feeney, M Semsey, S Kessel, M Goldberg, MB Adhya, S Oppenheim, AB AF Edgar, Rotem Rokney, Assaf Feeney, Morgan Semsey, Szabolcs Kessel, Martin Goldberg, Marcia B. Adhya, Sankar Oppenheim, Amos B. TI Bacteriophage infection is targeted to cellular poles SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; PHOSPHOTRANSFERASE SYSTEM; BACILLUS-SUBTILIS; GENOME SEQUENCE; OUTER-MEMBRANE; LAMBDA-DNA; PROTEIN; RECEPTOR; DIVISION; FTSH AB The poles of bacteria exhibit several specialized functions related to the mobilization of DNA and certain proteins. To monitor the infection of Escherichia coli cells by light microscopy, we developed procedures for the tagging of mature bacteriophages with quantum dots. Surprisingly, most of the infecting phages were found attached to the bacterial poles. This was true for a number of temperate and virulent phages of E. coli that use widely different receptors and for phages infecting Yersinia pseudotuberculosis and Vibrio cholerae. The infecting phages colocalized with the polar protein marker IcsA-GFP. ManY, an E. coli protein that is required for phage lambda DNA injection, was found to localize to the bacterial poles as well. Furthermore, labelling of lambda DNA during infection revealed that it is injected and replicated at the polar region of infection. The evolutionary benefits that lead to this remarkable preference for polar infections may be related to lambda's developmental decision as well as to the function of poles in the ability of bacterial cells to communicate with their environment and in gene regulation. C1 [Edgar, Rotem; Semsey, Szabolcs; Adhya, Sankar; Oppenheim, Amos B.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rokney, Assaf; Oppenheim, Amos B.] Hebrew Univ Jerusalem, Dept Mol Genet & Biotechnol, Hadassah Med Sch, IL-91120 Jerusalem, Israel. [Feeney, Morgan; Goldberg, Marcia B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Semsey, Szabolcs] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. [Kessel, Martin] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Edgar, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM edgarr@mail.nih.gov RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495 FU Intramural NIH HHS; NIAID NIH HHS [AI071240, AI35817, R01 AI035817, R21 AI071240] NR 39 TC 41 Z9 41 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2008 VL 68 IS 5 BP 1107 EP 1116 DI 10.1111/j.1365-2958.2008.06205.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 298WJ UT WOS:000255717500006 PM 18363799 ER PT J AU Ravni, A Vaudry, D Gerdin, MJ Eiden, MV Falluel-Morel, A Gonzalez, BJ Vaudry, H Eiden, LE AF Ravni, Aurelia Vaudry, David Gerdin, Matthew J. Eiden, Maribeth V. Falluel-Morel, Anthony Gonzalez, Bruno J. Vaudry, Hubert Eiden, Lee E. TI A cAMP-dependent, protein kinase A-independent signaling pathway mediating neuritogenesis through Egr1 in PC12 cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; CYCLASE-ACTIVATING POLYPEPTIDE; NEURITE OUTGROWTH; MAP KINASE; SUSTAINED ACTIVATION; REGULATED KINASE; RAP1 ACTIVATION; GENE-EXPRESSION; B-RAF; DIFFERENTIATION AB The neurotrophic peptide PACAP (pituitary adenylate cyclase-activating polypeptide) elevates cAMP in PC12 cells. Forskolin and dibutyryl cAMP mimic PACAP's neuritogenic and cell morphological effects, suggesting that they are driven by cAMP. Comparison of microarray expression profiles after exposure of PC12 cells to either forskolin, dibutyryl cAMP, or PACAP revealed a small group of cAMP-dependent target genes. Neuritogenesis induced by all three agents is protein kinase A (PKA)-independent [not blocked by N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89)] and extracellular signal-regulated kinase (ERK)-dependent [blocked by 1,4-diamino-2,3-dicyano-1,4-bis(methylthio) butadiene (U0126)], and therefore cAMP-dependent target genes potentially mediating neuritogenesis were selected for further analysis based on the pharmacological profile of their induction by PACAP (i.e., mimicking that of neuritogenesis). Small interfering RNA (siRNA) targeting one of these genes, Egr1, blocked PACAP-induced neuritogenesis, and siRNA targeting another, Vil2, blocked a component of the cell size increase elicited by PACAP. Neither siRNA blocked PACAP's PKA-dependent antiproliferative effects. PACAP signaling to neuritogenesis was also impaired by dominant-negative Rap1 expression but was not affected by inhibition of protein kinase C (PKC), indicating a G-protein-coupled receptor-mediated differentiation pathway distinct from the one activated by receptor tyrosine kinase ligands such as nerve growth factor (NGF), that involves both Rap1 and PKC. We have thus identified a cAMP-dependent, PKA-independent pathway proceeding through ERK that functions to up-regulate the transcription of two genes, Egr1 and Vil2, required for PACAP-dependent neuritogenesis and increased cell size, respectively. Dominant-negative Rap1 expression impairs both PACAP-induced neuritogenesis and Egr1 activation by PACAP, suggesting that cAMP elevation and ERK activation by PACAP are linked through Rap1. C1 [Ravni, Aurelia; Vaudry, David; Gerdin, Matthew J.; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. [Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. [Ravni, Aurelia; Vaudry, David; Falluel-Morel, Anthony; Gonzalez, Bruno J.; Vaudry, Hubert] Univ Rouen, INSERM, U413,Inst Fed Rech Multidisciplinaires Peptides 2, Lab Cellular & Mol Neuroendocrinol,European Inst, Mont St Aignan, France. RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-68, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov RI Gonzalez, Bruno/E-6103-2016; OI Vaudry, David/0000-0003-3567-7452; Eiden, Lee/0000-0001-7524-944X FU Intramural NIH HHS [Z01 MH002386-21, Z01 MH002386-22, ZIA MH002386-23]; NIMH NIH HHS [Z01 MH002386] NR 40 TC 53 Z9 55 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 2008 VL 73 IS 6 BP 1688 EP 1708 DI 10.1124/mol.107.044792 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 302QA UT WOS:000255982500012 PM 18362103 ER PT J AU Dragin, N Shi, ZQ Madan, R Karp, CL Sartor, MA Chen, C Gonzalez, FJ Nebert, DW AF Dragin, Nadine Shi, Zhanquan Madan, Rajat Karp, Christopher L. Sartor, Maureen A. Chen, Chi Gonzalez, Frank J. Nebert, Daniel W. TI Phenotype of the Cyp1a1/1a2/1b1(-/-) triple-knockout mouse SO MOLECULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-of-Toxicology CY MAR 25-29, 2007 CL Charlotte, NC SP Soc Toxicol ID ARYL-HYDROCARBON RECEPTOR; ARACHIDONIC-ACID METABOLITES; REACTIVE OXYGEN PRODUCTION; EPOXYEICOSATRIENOIC ACIDS; MESSENGER-RNA; SIGNALING PATHWAYS; EPITHELIAL-CELLS; LIPID MEDIATORS; AH RECEPTOR; CYTOCHROME-P450 AB Crossing the Cyp1a1/1a2(-/-) double- knockout mouse with the Cyp1b1(-/-) single- knockout mouse, we generated the Cyp1a1/1a2/1b1(-/-) triple-knockout mouse. In this triple-knockout mouse, statistically significant phenotypes (with incomplete penetrance) included slower weight gain and greater risk of embryolethality before gestational day 11, hydrocephalus, hermaphroditism, and cystic ovaries. Oral benzo[a] pyrene (BaP) daily for 18 days in the Cyp1a1/1a2(-/-) produced the same degree of marked immunosuppression as seen in the Cyp1a1(-/-) mouse; we believe this reflects the absence of intestinal CYP1A1. Oral BaP-treated Cyp1a1/1a2/1b1(-/-) mice showed the same "rescued" response as that seen in the Cyp1a1/1b1(-/-) mouse; we believe this reflects the absence of CYP1B1 in immune tissues. Urinary metabolite profiles were dramatically different between untreated triple-knockout and wild-type; principal components analysis showed that the shifts in urinary metabolite patterns in oral BaP-treated triple-knockout and wild-type mice were also strikingly different. Liver microarray cDNA differential expression (comparing triple-knockout with wild-type) revealed at least 89 genes up- and 62 genes down-regulated (P-value <= 0.00086). Gene Ontology "classes of genes" most perturbed in the untreated triple-knockout (compared with wild-type) include lipid, steroid, and cholesterol biosynthesis and metabolism; nucleosome and chromatin assembly; carboxylic and organic acid metabolism; metal-ion binding; and ion homeostasis. In the triple-knockout compared with the wild-type mice, response to zymosan-induced peritonitis was strikingly exaggerated, which may well reflect down-regulation of Socs2 expression. If a single common molecular pathway is responsible for all of these phenotypes, we suggest that functional effects of the loss of all three Cyp1 genes could be explained by perturbations in CYP1-mediated eicosanoid production, catabolism and activities. C1 [Dragin, Nadine; Shi, Zhanquan; Sartor, Maureen A.; Nebert, Daniel W.] Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Dragin, Nadine; Shi, Zhanquan; Sartor, Maureen A.; Nebert, Daniel W.] Univ Cincinnati, Med Ctr, Ctr Environm Genet, Cincinnati, OH 45267 USA. [Madan, Rajat; Karp, Christopher L.] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH USA. [Chen, Chi; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nebert, DW (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA. EM dan.nebert@uc.edu OI Karp, Christopher/0000-0002-0832-2659 FU NIEHS NIH HHS [P30 ES006096, P30 ES006096-139007, P30 ES006096-149007, P30-ES06096, R01 ES008147, R01 ES008147-07, R01 ES008147-07S1, R01 ES008147-08, R01 ES014403, R01 ES014403-03, R01 ES014403-03S1, R01-ES014403, R01-ES08147] NR 70 TC 35 Z9 35 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 2008 VL 73 IS 6 BP 1844 EP 1856 DI 10.1124/mol.108.045658 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 302QA UT WOS:000255982500026 PM 18372398 ER PT J AU Rao, JS Lee, HJ Rapoport, SI Bazinet, RP AF Rao, J. S. Lee, H-J Rapoport, S. I. Bazinet, R. P. TI Mode of action of mood stabilizers: is the arachidonic acid cascade a common target? SO MOLECULAR PSYCHIATRY LA English DT Review DE bipolar disorder; mood stabilizer; arachidonic acid; prostaglandin; phospholipase; cyclooxygenase ID BIPOLAR AFFECTIVE-DISORDER; DNA-BINDING ACTIVITY; RAT FRONTAL-CORTEX; POSITRON-EMISSION-TOMOGRAPHY; CYTOSOLIC PHOSPHOLIPASE A(2); LITHIUM MAINTENANCE TREATMENT; POLYUNSATURATED FATTY-ACIDS; CONTROLLED 18-MONTH TRIAL; PLACEBO-CONTROLLED TRIALS; MANIC-DEPRESSIVE ILLNESS AB Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers ( lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid ( AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A(2) gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E(2). Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease. C1 [Bazinet, R. P.] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada. [Rao, J. S.; Lee, H-J; Rapoport, S. I.; Bazinet, R. P.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bazinet, RP (reprint author), Univ Toronto, Fac Med, Dept Nutr Sci, FitzGerald Bldg,150 Coll St,Room 306, Toronto, ON M5S 3E2, Canada. EM richard.bazinet@utoronto.ca RI Rao, Jagadeesh/C-1250-2009 FU Intramural NIH HHS NR 178 TC 66 Z9 66 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2008 VL 13 IS 6 BP 585 EP 596 DI 10.1038/mp.2008.31 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 302FE UT WOS:000255953400003 PM 18347600 ER PT J AU Wiedholz, LM Owens, WA Horton, RE Feyder, M Karlsson, RM Hefner, K Sprengel, R Celikel, T Daws, LC Holmes, A AF Wiedholz, L. M. Owens, W. A. Horton, R. E. Feyder, M. Karlsson, R-M Hefner, K. Sprengel, R. Celikel, T. Daws, L. C. Holmes, A. TI Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and 'schizophrenia-related' behaviors SO MOLECULAR PSYCHIATRY LA English DT Article DE glutamate; dopamine; AMPA GluR1; novelty; hyperactivity; prepulse inhibition; dopamine transporter ID SPATIAL REFERENCE MEMORY; A-DEFICIENT MICE; SYNAPTIC PLASTICITY; KNOCKOUT MICE; DOPAMINE TRANSPORTER; PREPULSE INHIBITION; PREFRONTAL CORTEX; EXPRESSION; MOUSE; HYPERACTIVITY AB There is growing evidence implicating dysfunctional glutamatergic neurotransmission and abnormal interactions between the glutamate and dopamine (DA) systems in the pathophysiology of various neuropsychiatric disorders including schizophrenia. The present study evaluated knockout (KO) mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) GluR1 receptor subunit for a range of behaviors considered relevant to certain symptoms of schizophrenia. KO showed locomotor hyperactivity during exposure to open field and in response to a novel object, but normal activity in a familiar home cage. Open field locomotor hyperactivity in KO was effectively normalized to WT levels by treatment with the DA antagonist and neuroleptic haloperidol, while locomotor stimulant effects of the NMDA receptor antagonist MK-801 were absent in KO. Social behaviors during a dyadic conspecific encounter were disorganized in KO. KO showed deficits in prepulse inhibition of the acoustic startle response. In vivo chronoamperometric measurement of extracellular DA clearance in striatum demonstrated retarded clearance in KO. These data demonstrate behavioral abnormalities potentially pertinent to schizophrenia in GluR1 KO, together with evidence of dysregulated DA function. Present findings provide novel insight into the potential role of GluR1, AMPA receptors and glutamate x DA interactions in the pathophysiology of schizophrenia and other neuropsychiatric conditions. C1 [Wiedholz, L. M.; Feyder, M.; Karlsson, R-M; Hefner, K.; Holmes, A.] NIAAA, NIH, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Owens, W. A.; Horton, R. E.; Daws, L. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Sprengel, R.; Celikel, T.] Max Planck Inst Med Res, Heidelberg, Germany. RP Holmes, A (reprint author), NIAAA, NIH, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Lane,2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov OI Hefner, Kathryn/0000-0002-5208-7860 FU Intramural NIH HHS; NIMH NIH HHS [R01-MH64489] NR 56 TC 79 Z9 80 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2008 VL 13 IS 6 BP 631 EP 640 DI 10.1038/sj.mp.4002056 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 302FE UT WOS:000255953400008 PM 17684498 ER PT J AU Kaneto, M Krisfalusi, M Eddy, EM O'Brien, DA Miki, K AF Kaneto, Masako Krisfalusi, Michelle Eddy, Edward M. O'Brien, Deborah A. Miki, Kiyoshi TI Bicarbonate-induced phosphorylation of p270 protein in mouse sperm by cAMP-Dependent protein kinase SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE PKA; substrate; AKAP; capacitation ID SOLUBLE ADENYLYL-CYCLASE; MEDIATED SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; PLASMA-MEMBRANE; FIBROUS SHEATH; ANCHORING PROTEIN; MAMMALIAN SPERM; BOAR SPERM; RAT SPERM; LIPID RAFTS AB Signaling by cAMP-dependent protein kinase (PKA) plays an important role in the regulation of mammalian sperm motility. However, it has not been determined how PKA signaling leads to changes in motility, and specific proteins responsible for these changes have not yet been identified as PKA substrates. Anti-phospho-(Ser/Thr) PKA substrate antibodies detected a sperm protein with a relative molecular weight of 270,000 (p270), which was phosphorylated within 1 min after incubation in a medium supporting capacitation. Phosphorylation of p270 was induced by bicarbonate or a cAMP analog, but was blocked by the PKA inhibitor H-89, indicating that p270 is likely a PKA substrate in sperm. In addition, phosphorylation of p270 was inhibited by stearated peptide st-Ht31, suggesting that p270 is phosphorylated by PKA associated with an A-kinase anchoring protein (AKAP). AKAP4 is the major fibrous sheath protein of mammalian sperm and tethers regulatory subunits of PKA to localize phosphorylation events. Phosphorylation of p270 occurred in sperm lacking AKAP4, suggesting that AKAP4 is not involved directly in the phosphorylation event. Phosphorylated p270 was enriched in fractionated sperm tails and appeared to be present in multiple compartments including a detergent-resistant membrane fraction. PKA phosphorylation of p270 within 1 min of incubation under capacitation conditions suggests that this protein may have an important role in the initial signaling events that lead to the activation and subsequent hyperactivation of sperm motility. C1 [Kaneto, Masako; O'Brien, Deborah A.; Miki, Kiyoshi] Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Kaneto, Masako; Krisfalusi, Michelle; O'Brien, Deborah A.; Miki, Kiyoshi] Univ N Carolina, Sch Med, Reprod Biol Lab, Dept Pediat, Chapel Hill, NC 27599 USA. [Kaneto, Masako] Shionogi & Co Ltd, Res & Dev Labs, Osaka, Japan. [Eddy, Edward M.] NIH, Gamete Biol Sect, Reprod & Dev Toxicol Lab, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Miki, K (reprint author), Univ N Carolina, Sch Med, Dept Cell & Dev Biol, CB 7090,216 Taylor Hall, Chapel Hill, NC 27599 USA. EM miki@med.unc.edu FU Intramural NIH HHS; NICHD NIH HHS [U54 HD35041, U54 HD035041] NR 45 TC 19 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JUN PY 2008 VL 75 IS 6 BP 1045 EP 1053 DI 10.1002/mrd.20839 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 296UU UT WOS:000255572100009 PM 18357561 ER PT J AU Zheng, CY Vitolo, JM Zhang, WT Mineshiba, F Chiorini, JA Baum, BJ AF Zheng, Changyu Vitolo, Joseph M. Zhang, Weitian Mineshiba, Fumi Chiorini, John A. Baum, Bruce J. TI Extended transgene expression from a nonintegrating adenoviral vector containing retroviral elements SO MOLECULAR THERAPY LA English DT Article ID GENE-THERAPY; SALIVARY-GLANDS; CELL-LINE; PAROTID-GLAND; DNA; INTEGRATION; INFECTION; DELIVERY; CHEMOTHERAPY; EFFICIENCY AB We studied the effects of specific retroviral elements in a first-generation serotype 5 adenoviral ( Ad5) vector, AdLTR(2)EF1 alpha-hEPO. This vector contains 858 base pair ( bp) [251-bp envelope sequence plus 607-bp long-terminal repeat ( LTR)] from Moloney murine leukemia virus ( MoMLV), upstream of the human elongation factor-1 alpha ( EF1 alpha) promoter and human erythropoietin ( hEPO) cDNA, with the LTR sequence downstream of the polyadenylation signal. We compared expression of AdLTR(2)EF1 alpha-hEPO with corresponding expressions of two conventional Ad5 vectors, AdEF1 alpha-hEPO and AdCMV-hEPO, in vivo in submandibular glands in rats. Both the conventional vectors yielded low serum hEPO levels by day 7, and little change in hematocrits. In contrast, after receiving AdLTR(2)EF1 alpha-hEPO, the rats showed elevated hEPO levels and hematocrits for 1-3 months. In vitro studies showed that the integration efficiencies of all the vectors were similar (similar to 10(-3)). Approximately 0.1% of the vector genomes were present 1 year after delivery in the case of each of the three vectors, primarily as intact linear double-strand DNA. The unique results seen with AdLTR(2)EF1 alpha-hEPO are partly because of LTR enhancer activity. However, other cis-acting activity, which is not immunomodulatory but nevertheless influences promoter methylation, appears to be involved. A vector such as AdLTR(2)EF1 alpha-hEPO may prove useful in clinical applications in which extended, but not "permanent," transgene expression is desirable. C1 [Zheng, Changyu; Vitolo, Joseph M.; Zhang, Weitian; Mineshiba, Fumi; Chiorini, John A.; Baum, Bruce J.] Natl Inst Dental & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dental & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Intramural NIH HHS [, Z01 DE000336-27] NR 36 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2008 VL 16 IS 6 BP 1089 EP 1097 DI 10.1038/mt.2008.56 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 306KR UT WOS:000256247500017 PM 18388914 ER PT J AU Wang, H Tessmer, I Croteau, DL Erie, DA Van Houten, B AF Wang, Hong Tessmer, Ingrid Croteau, Deborah L. Erie, Dorothy A. Van Houten, Bennett TI Functional characterization and atomic force microscopy of a DNA repair protein conjugated to a quantum dot SO NANO LETTERS LA English DT Article ID EXCISION-REPAIR; SINGLE-MOLECULE; BINDING; UVRB; COMPLEX; BIOCONJUGATION; PROCESSIVITY; CONSTANTS AB Quantum dots (QDs) possess highly desirable optical properties that make them ideal fluorescent labels for studying the dynamic behavior of proteins. However, a lack of characterization methods for reliably determining protein-quantum dot conjugate stoichiometry and functionality has impeded their widespread use in single-molecule studies. We used atomic force microscopic (AFM) imaging to demonstrate the 1:1 formation of UvrB-QD conjugates based on an antibody-sandwich method. We show that an agarose gel-based electrophoresis mobility shift assay and AFM can be used to evaluate the DNA binding function of UvrB-QD conjugates. Importantly, we demonstrate that quantum dots can serve as a molecular marker to unambiguously identify the presence of a labeled protein in AFM images. C1 [Tessmer, Ingrid; Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Tessmer, Ingrid; Erie, Dorothy A.] Univ N Carolina, Curriculum Mat Sci, Chapel Hill, NC 27599 USA. [Wang, Hong; Croteau, Deborah L.] NIEHS, NIH, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Erie, DA (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM derie@unc.edu; vanhout1@niehs.nih.gov RI Wang, Hong/F-3164-2014 OI Wang, Hong/0000-0003-0165-3559 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM079480, R01 GM079480-03] NR 34 TC 29 Z9 30 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD JUN PY 2008 VL 8 IS 6 BP 1631 EP 1637 DI 10.1021/nl080316l PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 313LL UT WOS:000256742000013 PM 18444686 ER PT J AU Szabo, E AF Szabo, Eva TI Primer: first do no harm - when is it appropriate to plan a cancer prevention clinical trial? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE carcinogenesis; chemoprevention; clinical trials; risk assessment; risk : benefit ID RANDOMIZED CONTROLLED-TRIAL; PHASE IIB TRIAL; LUNG-CANCER; BREAST-CANCER; COLORECTAL ADENOMAS; BETA-CAROTENE; CYCLOOXYGENASE-2 INHIBITOR; CARDIOVASCULAR EVENTS; VITAMIN-E; RISK AB Abundant preclinical and clinical data suggest that cancer is a preventable disease; however, few, if any, of the medical interventions available are completely without adverse effects or risk to the patient. This statement is especially true with regard to phenotypically healthy but high-risk populations. Balancing the risks from interventions with the risk of future life-threatening disease is particularly challenging because no standardized methodologies to perform such calculations exist. It is critical, therefore, to establish a framework for determining when interventions show sufficient promise of efficacy and sufficient safety to justify their testing in clinical trials. Systematic review of all available preclinical, epidemiological, and clinical data, along with a mechanistic understanding of the biology of the disease under study, is mandatory before clinical trials are embarked upon. This Review identifies the issues that are critical for decision-making when clinical trials in human beings are being contemplated and provides a framework that can be applied in making these decisions. C1 NCI, Canc Prevent Div, Lung & Upper Aerodigest Canc Res Grp, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Canc Prevent Div, Lung & Upper Aerodigest Canc Res Grp, 6130 Execut Blvd,Room 2132, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov NR 51 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUN PY 2008 VL 5 IS 6 BP 348 EP 356 DI 10.1038/ncponc1123 PG 9 WC Oncology SC Oncology GA 306DT UT WOS:000256229200011 PM 18446144 ER PT J AU Ling, SM AF Ling, S. M. TI Does acupuncture improve symptoms in patients with osteoarthritis who are awaiting knee replacement surgery? SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Editorial Material DE acupuncture; joint replacement; knee pain; osteoarthritis; physiotherapy ID JOINT REPLACEMENT; STATES C1 [Ling, S. M.] NIA, Clin Res Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Ling, SM (reprint author), NIA ASTRA UNIT Harbor Hosp, Clin Res Branch, Baltimore, MD 21225 USA. EM lingsh@mail.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD JUN PY 2008 VL 4 IS 6 BP 286 EP 287 DI 10.1038/ncprheum0795 PG 2 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 307GX UT WOS:000256308500003 PM 18398410 ER EF