FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kaye, FJ AF Kaye, Frederic J. TI Emerging biology of malignant salivary gland tumors offers new insights into the classification and treatment of mucoepidermoid cancer - Commentary SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID MECT1-MAML2 FUSION ONCOGENE; WARTHINS TUMOR; HUMAN HOMOLOG; GENE FUSION; CARCINOMA; ACTIVATION; MUTATIONS; SURVIVORS C1 NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. RP Kaye, FJ (reprint author), USN Hosp, NCI, Naval Med Oncol Branch, Bethesda, MD 20814 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011 NR 31 TC 16 Z9 16 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 JUL 1 PY 2006 VL 12 IS 13 BP 3878 EP 3881 DI 10.1158/1078-0432.CCR-06-0791 PG 4 WC Oncology SC Oncology GA 062FR UT WOS:000238930500003 PM 16818681 ER PT J AU Benakanakere, I Besch-Williford, C Schnell, J Brandt, S Ellersieck, MR Molinolo, A Hyder, SM AF Benakanakere, Indira Besch-Williford, Cynthia Schnell, Jennifer Brandt, Sandra Ellersieck, Mark R. Molinolo, Alfredo Hyder, Salman M. TI Natural and synthetic progestins accelerate 7,12-dimethylbenz[a] anthracene-initiated mammary tumors and increase angiogenesis in Sprague-Dawley rats SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HUMAN BREAST-CANCER; HORMONE REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; LONG-TERM SURVIVAL; MEDROXYPROGESTERONE ACETATE; SIGNAL-TRANSDUCTION; CELL-PROLIFERATION; EXPRESSION AB Purpose: Synthetic progestins are widely used therapeutically; however, there is controversy regarding their proliferative effects. We used a rat 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary tumor model to test the hypothesis that progestins increase angiogenesis and as a result decrease the latency period and increase the multiplicity of mammary tumors. Experimental Design: Medroxyprogesterone acetate (MPA) pellets were implanted 2, 4, or 6 weeks after DMBA exposure; RU-486 was given 3 days before MPA. Experiments were concluded 70 days after DMBA administration. Results: MPA exposure 4 or 6 weeks after DMBA reduced the latency period for appearance of tumors in a dose-dependent manner and increased tumor incidence. Administration of MPA 2 weeks after DMBA administration reduced tumor incidence and was protective. Progesterone did not reduce the latency period but significantly increased tumor incidence. RU-486 delayed the latency period and decreased tumor incidence in animals exposed to MPA at 4 weeks after DMBA treatment, indicating that the progesterone receptor may be partially responsible for transmission of proliferative signals. RU-486 also delayed the latency period but failed to reduce overall tumor incidence when animals were exposed to MPA at 6 weeks after DMBA treatment, indicating that other factors may also control MPA-induced acceleration. Whereas MPA-accelerated tumors were both intraductal and tubular, progesterone-accelerated and/or DMBA-induced tumors were tubular. Progestin treatment increased vascular endothelial growth factor expression within tumors in a ligand- and cell type-dependent manner and increased angiogenesis in correlation with vascular endothelial growth factor expression. No mammary tumors or progesterone receptor were detected in DMBA-treated ovariectomized rats regardless of progestin administration. Conclusions: We propose that progestins can accelerate the development of mammary tumors and that antiangiogenic agents and/or the use of antiprogestins that can reduce tumor incidence might be a viable therapeutic option for treatment of progestin-accelerated tumors. The model described here is a potentially useful preclinical model for rapidly screening such compounds. C1 Univ Missouri, Dalton Cardiovasc Res Ctr, Columbia, MO 65211 USA. Univ Missouri, Dept Biomed Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Vet Pathol, Columbia, MO 65211 USA. Univ Missouri, Dept Stat, Columbia, MO 65211 USA. NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. RP Hyder, SM (reprint author), Univ Missouri, Dalton Cardiovasc Res Ctr, 134 Res Pk Dr, Columbia, MO 65211 USA. EM hyders@missouri.edu FU NCI NIH HHS [CA-86916] NR 43 TC 21 Z9 21 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 JUL 1 PY 2006 VL 12 IS 13 BP 4062 EP 4071 DI 10.1158/1078-0432.CCR-06-0427 PG 10 WC Oncology SC Oncology GA 062FR UT WOS:000238930500028 PM 16818706 ER PT J AU Hortin, GL Jortani, SA Ritchie, JC Valdes, R Chan, DW AF Hortin, GL Jortani, SA Ritchie, JC Valdes, R Chan, DW TI Proteomics: A new diagnostic frontier SO CLINICAL CHEMISTRY LA English DT Review ID HUMAN PLASMA PROTEOME; MASS-SPECTROMETRY; AFFINITY-CHROMATOGRAPHY; BIOMARKER DISCOVERY; HUMAN SERUM; PROTEINS; CANCER; SAMPLES; COMBINATION; STANDARDS AB Background: Analysis of proteins has been an integral part of the field of clinical chemistry for decades. Recent advances in technology and complete identification of the human genome sequence have opened. up new opportunities for analysis of proteins for clinical diagnostic purposes. Methods: Content of a recent conference of proteomics is summarized. Results: New analytical methods allow the simultaneous analysis of a large number of proteins in biological fluids such as serum and plasma, offering partial views of the complete set of proteins or proteome. Plasma presents many analytical challenges, such as the complexity of components, predominance of a few major components, and the large concentration range of components, but the number of proteins that can be detected in plasma has expanded dramatically from hundreds to thousands. At the same time, there is increased capability to detect structural variations of proteins. Recent studies also identified the, presence of complex sets of small protein fragments, in plasma. This set of protein fragments, the fragmentome or peptidome, is potentially a rich, source of information about physiologic and disease processes. Conclusions: Advances in proteomics offer great promise for the discovery of markers that might serve as the basis for new clinical laboratory tests. There are many challenges,, however, in the translation of newly discovered markers into clinical laboratory tests. (c) 2006 American Association for Clinical Chemistry. C1 NIH, Dept Lab Med, Intramural Res Program, NIH Clin Ctr, Bethesda, MD 20892 USA. Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40292 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Intramural Res Program, NIH Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 29 TC 70 Z9 75 U1 0 U2 12 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 JUL PY 2006 VL 52 IS 7 BP 1218 EP 1222 DI 10.1373/clinchem.2006.067280 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 059IF UT WOS:000238725800002 PM 16675505 ER PT J AU Hortin, GL AF Hortin, GL TI The MALDI-TOF mass spectrometric view of the plasma proteome and peptidome SO CLINICAL CHEMISTRY LA English DT Review ID ASSISTED-LASER-DESORPTION/IONIZATION; AMINO-ACID-SEQUENCE; CANCER BIOMARKER DISCOVERY; STAGE OVARIAN-CANCER; ACUTE-PHASE PROTEINS; PROSTATE-CANCER; MODIFIED BETA-2-MICROGLOBULIN; PROFILING EXPERIMENTS; DENSITY-LIPOPROTEIN; REFERENCE SPECIMENS AB Background: Matrix-assisted laser desorption/ionization time-of-flight mass,spectrometry (MALDI-TOF MS) and the related technique, surface-enhanced laser desorption/ionization (SELDI)-TOF MS, are being applied widely to analyze serum or plasma specimens for potential disease markers. Methods: Reports on the basic principles and applications of MALDI-TOF MS were reviewed and related to information on abundance and masses of major plasma proteins. Outcomes: MALDI-TOF MS is a particle-counting method that responds to molar abundance, and ranking of plasma proteins by molar abundance increases the rank of small proteins relative to traditional. ranking by mass abundance. Detectors for MALDI-TOF MS augment the bias for detecting smaller components by yielding stronger signals for an equivalent number of small vs large ions. Consequently, MALDI-TOF MS is a powerful tool for surveying small proteins and peptides comprising the, peptidome or fragmentome, opening this new,realm for analysis. It is complementary to techniques such as electrophoresis and HPLC, which have a bias for detecting larger molecules. Virtually all of the potential markers identified by MALDI-TOF MS to date represent forms of the most abundant plasma proteins. Conclusions: Analyses of serum or plasma by MALDI-TOF MS provide new information mainly about small proteins and peptides with high molar abundance. The spectrum of observed proteins and peptides suggests value for applications such as assessment of cardiovascular risk, nutritional status, liver injury, kidney failure, and systemic immune responses rather than early detection of cancer. Extending analysis by MALDI-TOF MS to lower abundance components, such as markers for early-stage cancers, probably will require more extensive specimen fractionation before analysis. (c) 2006 American Association for Clinical Chemistry. C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov FU Intramural NIH HHS NR 126 TC 239 Z9 252 U1 9 U2 74 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 JUL PY 2006 VL 52 IS 7 BP 1223 EP 1237 DI 10.1373/clinchem.2006.069252 PG 15 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 059IF UT WOS:000238725800003 PM 16644871 ER PT J AU Gori, AM Sofi, F Corsi, AM Gazzini, A Sestini, I Lauretani, F Bandinelli, S Gensini, GF Ferrucci, L Abbate, R AF Gori, AM Sofi, F Corsi, AM Gazzini, A Sestini, I Lauretani, F Bandinelli, S Gensini, GF Ferrucci, L Abbate, R TI Predictors of vitamin B-6 and folate concentrations in older persons: The InCHIANTI study SO CLINICAL CHEMISTRY LA English DT Article ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; RISK-FACTOR; CARDIOVASCULAR RISK; INFLAMMATORY MARKERS; PLASMA HOMOCYSTEINE; EXCESS INCIDENCE; SERUM FOLATE; LARGE-SCALE; FOLIC-ACID AB Background: Low dietary intake and low serum concentrations of vitamin B-6 and/or folate are associated with increased risk of vascular events, possibly because of their association with inflammation, which plays a crucial role in the pathogenesis of cardiovascular diseases. Methods: Using data from 1320 participants in the population-based InCHIANTI study (586 men and 734 women; median age, 69 years; range, 21-102 years) for whom complete data on folate, vitamin B6, inflammatory markers, 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T sequence variant, and important covariates were available; we evaluated the association of inflammatory markers with circulating concentrations of vitamin B6 and folate, independently of dietary vitamin intake, circulating vitamin concentrations, and MTHFR C677T sequence variant. Results: According to multiple linear regression analysis, C-reactive protein and interleukin-6 receptor were strongly and negatively associated with circulating vitamin B-6 but not with folate concentrations, independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, dietary nutrient intake, and circulating homocysteine and vitamin concentrations. Serum folate concentrations were related to MTHFR 677 TT genotype in persons with folate intake in the lowest tertile (< 221.2 mu g/day). Vitamin C and retinol intakes were strongly and positively associated with serum folate concentrations independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, homocysteine plasma concentrations, dietary nutrient intakes, serum vitamin B-6 and vitamin B-12 concentrations, and MTHFR C677T sequence variant. Conclusions: Low serum vitamin B6, but not serum folate, concentrations are independent correlates of the proinflammatory state, and both are influenced by antioxidant reserves. (c) 2006 American Association for Clinical Chemistry. C1 Univ Florence, Dept Med & Surg Crit Care, I-50134 Florence, Italy. Univ Florence, Multidisciplinary Ctr Res Food Sci GRA, I-50134 Florence, Italy. Fdn Don Carlo Gnocchi Onlus, IRCCS Impruneta, Ctr S Maria Ulivi, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. Azienda Sanitaria Firenze, Florence, Italy. NIA, Longitudinal Studies Sect, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Gori, AM (reprint author), Univ Florence, Dept Med & Surg Crit Care, Viale Morgagni 85, I-50134 Florence, Italy. EM annamaria.gori@unifi.it RI Sofi, Francesco/J-3941-2016; Lauretani, Fulvio/K-5115-2016 OI Sofi, Francesco/0000-0001-7113-7424; Gori, annamaria.gori@unifi.it/0000-0001-6857-5861; Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413]; NIMHD NIH HHS [R01 MD009164] NR 36 TC 29 Z9 30 U1 1 U2 4 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 JUL PY 2006 VL 52 IS 7 BP 1318 EP 1324 DI 10.1373/clinchem.2005.066217 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 059IF UT WOS:000238725800015 PM 16690736 ER PT J AU Adams, PC Passmore, L Chakrabarti, S Reboussin, DM Acton, RT Barton, JC Mclaren, GD Eckfeldt, JH Dawkins, FW Gordeuk, VR Harris, EL Leiendecker-Foster, C Gossman, E Sholinsky, P AF Adams, Paul C. Passmore, Leah Chakrabarti, Subrata Reboussin, David M. Acton, Ronald T. Barton, James C. Mclaren, Gordon D. Eckfeldt, John H. Dawkins, Fitzroy W. Gordeuk, Victor R. Harris, Emily L. Leiendecker-Foster, Catherine Gossman, Elaine Sholinsky, Phyliss CA Hemochromatosis Iron Overload TI Liver diseases in the hemochromatosis and iron overload screening study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; GENETIC HEMOCHROMATOSIS; TRANSFERRIN SATURATION; AFRICAN-AMERICANS; HEPATITIS-C; POPULATION; DIAGNOSIS; PREVALENCE; MANAGEMENT; MUTATIONS AB Background & Aims: The Hemochromatosis and Iron Overload Screening (HEIRS) Study screened 101,168 primary care participants for iron overload with serum transferrin saturation (TS), ferritin, and C282Y and H63D mutations of the HFE gene. Methods: All C282Y homozygotes and participants with an increased TS (>45% women, >50% men) and serum ferritin level (> 200 mu g/L women, >300 mu g/L men) were recalled for a clinical history and physical examination, and blood tests including alanine transaminase (ALT) and aspartate transaminase levels. Hepatitis B surface antigen and anti-hepatitis C virus were measured if the ALT level was increased (>31 IU/L in women, >40 IU/L in men). Results: In the group of participants selected to return for clinical examination because of increased TS and ferritin levels, ALT increases and anti-hepatitis C virus were found in 95 of 284 (33%) African Americans, 50 of 466 (11%) Asian and Pacific Islanders, 2:1 of 120 (18%) Hispanics, and 40 of 477 (8.4%) Caucasians. ALT increases and hepatitis B surface antigen were detected in 24 of 466 (5%) Asian and Pacific Islanders, :10 of 284 (3.5%) African Americans, 3 of 120 (2.5%) Hispanics, and 2 of 477 (.42%) Caucasians. Of 86 liver biopsy specimens obtained for clinical purposes, 53 were reviewed by a single study pathologist. Liver fibrosis (stage 3 or 4) was present in 2 of 11 (18.2%) C282Y homozygotes that underwent central review and 2 of 302 (.66%) C282Y homozygotes attending the clinical examination. Conclusions: Screening for iron overload with ferritin and TS detects persons with viral hepatitis and other types of liver disease. A minimum of .66% C282Y homozygotes have liver fibrosis. C1 London Hlth Sci Ctr, Dept Pathol & Med, London, ON, Canada. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. So Iron Disorders Ctr, Birmingham, AL USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Howard Univ, Dept Med, Washington, DC 20059 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Kaiser Permanente, Dept Gastroenterol, Portland, OR USA. NHLBI, Epidemiol & Biometry Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Adams, PC (reprint author), Univ Hosp, Dept Med, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM padams@uwo.ca FU NCRR NIH HHS [5M01-RR-00827-29, M01-RR00032, M01-RR-10284]; NHLBI NIH HHS [N01-HC-05191, N01-HC-05190, N01-HC-05185, UH1-HL-03679-05, N01-HC-05188, N01-HC-05186, N01-HC-05189, N01-HC-05192] NR 34 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2006 VL 4 IS 7 BP 918 EP 923 DI 10.1016/j.cgh.2006.04.013 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 066AU UT WOS:000239202600021 PM 16797244 ER PT J AU Musso, C Javor, E Cochran, E Balow, JE Gorden, P AF Musso, Carla Javor, Edward Cochran, Elaine Balow, James E. Gorden, Phillip TI Spectrum of renal diseases associated with extreme forms of insulin resistance SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID DEPENDENT DIABETES-MELLITUS; CONGENITAL GENERALIZED LIPODYSTROPHY; CLINICAL-FEATURES; NEPHROPATHY; PROGRESSION; RECEPTOR; COMPLICATIONS; MICROALBUMINURIA; TRANSPLANTATION; AUTOANTIBODIES AB Diabetic nephropathy is the leading cause of ESRD in the United States. Why the pathogenic mechanisms lead to nephropathy in certain patients with type 1 and 2 diabetes and spare others is unclear, but it is clear that hyperglycemia and glomerular hyperfiltration are important factors. In patients with syndromes of extreme insulin resistance, proteinuric forms of renal disease are common, but it is surprising to find that the renal pathology usually is not diabetic nephropathy. For instance, in the lipodystrophy syndromes, membranoproliferative glomerulonephritis type 1 and type 2, focal segmental glomerulosclerosis, and also diabetic nephropathy are seen. In the syndromes of autoantibodies to the insulin receptor, the various forms of lupus glomerulonephritis are seen. Even in patients with type 2 diabetes, the renal pathology may not be diabetic nephropathy. Therefore, in patients with syndromic forms of insulin resistance and type 2 diabetes, renal biopsy has an important role in defining the pathology that leads to proteinuric nephropathy and in formulating a therapeutic approach. It is the purpose of this article to review these unusual aspects of proteinuric nephropathy in patients with diabetes. C1 NIDDK, CEB, NIH, Bethesda, MD 20892 USA. NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Gorden, P (reprint author), NIDDK, CEB, NIH, 9000 Rockville Pike,CRC Room 6-5952, Bethesda, MD 20892 USA. EM PhillipG@intra.niddk.nih.gov FU Intramural NIH HHS NR 40 TC 22 Z9 23 U1 0 U2 2 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2006 VL 1 IS 4 BP 616 EP 622 DI 10.2215/CJN.01271005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 108LQ UT WOS:000242241700004 PM 17699267 ER PT J AU Miranda, PC Lomarev, M Hallett, M AF Miranda, Pedro Cavaleiro Lomarev, Mikhail Hallett, Mark TI Modeling the current distribution during transcranial direct current stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE stimulation; electric; direct current; polarization; transcranial; motor cortex ID HUMAN MOTOR CORTEX; CURRENT-DENSITY DISTRIBUTIONS; APPLIED ELECTRIC-FIELDS; IN-VIVO MEASUREMENT; EIT-BASED METHOD; ELECTROMAGNETIC-FIELDS; MAGNETIC STIMULATION; LIMITING EXPOSURE; CEREBRAL-CORTEX; HUMAN BRAIN AB Objective: To investigate the spatial distribution of the magnitude and direction of the current density in the human head during transcranial direct current stimulation (tDCS). Methods: The current density distribution was calculated using a numerical method to implement a standard spherical head model into which current was injected by means of large electrodes. The model was positioned in 'MNI space' to facilitate the interpretation of spatial coordinates. Results: The magnitude and direction of the current density vector are illustrated in selected brain slices for four different electrode montages. Approximately half of the current injected during tDCS is shunted through the scalp, depending on electrode dimension and position. Using stimulating currents of 2.0 mA, the magnitude of the current density in relevant regions of the brain is of the order of 0.1 A/m(2), corresponding to an electric field of 0.22 V/m. Conclusions: Calculations based on a spherical model of the head can provide useful information about the magnitude and direction of the current density vector in the brain during tDCS, taking into account the geometry and position of the electrodes. Despite the inherent limitations of the spherical head model, the calculated values are comparable to those used in the most recent in vitro studies on modulation of neuronal activity. Significance: The methodology presented in this paper may be used to assess the current distribution during tDCS using new electrode montages, to help optimize montages that target a specific region of the brain or to preliminarily investigate compliance with safety guidelines. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Lisbon, Fac Ciencias, Inst Biofis & Engn Biomed, P-1749016 Lisbon, Portugal. NINDS, MNB, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Miranda, PC (reprint author), Univ Lisbon, Fac Ciencias, Inst Biofis & Engn Biomed, Campo Grande, P-1749016 Lisbon, Portugal. EM pcmiranda@fc.ul.pt RI Miranda, Pedro/A-5643-2013 OI Miranda, Pedro/0000-0002-6793-8111 NR 43 TC 316 Z9 325 U1 0 U2 36 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2006 VL 117 IS 7 BP 1623 EP 1629 DI 10.1016/j.clinph.2006.04.009 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KB UT WOS:000239227100026 PM 16762592 ER PT J AU Siegel, RM Bien, J Lichtenstein, P Davis, J Khoury, JC Knight, JE Kiely, M Bernier, J AF Siegel, Robert M. Bien, James Lichtenstein, Philip Davis, James Khoury, Jane C. Knight, Jamie E. Kiely, Michele Bernier, Jeralyn TI A safety-net antibiotic prescription for otitis media: The effects of a PBRN study on patients and practitioners SO CLINICAL PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-04, 2004 CL San Francisco, CA SP Pediat Acad Soc ID YOUNG-CHILDREN; METAANALYSIS; AMOXICILLIN; MANAGEMENT; TRIAL AB Pediatricians can decrease antibiotic use by treating acute otitis media (AOM) with a safety-net antibiotic prescription (SNAP). This study assessed whether the practitioners of the Practice-Based Research Network who participated in the study continued to use the SNAP and report a 60-day follow-up of the study patients. Charts were reviewed of study patients for 60 days following study enrollment. A survey on antibiotic use for AOM was mailed to the 17 study practitioners (SP) and 30 randomly selected community pediatricians (CP). Eight of the SP used the SNAP more than 20 times over the year following the study vs 1 of the CP. Sixty-two percent of patients never received antibiotics. The recurrence/relapse rate was greater in children younger than 2 years old compared to those older, 34% vs 10%. Practitioners who participate in a Practice-Based Research Network study are more likely to use a study intervention than others. C1 Cincinnati Childrens Hosp Med Ctr, Div Gen & Community Pediat, Cincinnati Pediat Res Grp, Cincinnati, OH 45229 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Div Epidemiol & Biostat, Cincinnati, OH 45267 USA. NIH, Div Epidemiol Stat & Prevent Res, ICHD, DHHS, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Gen & Community Pediat, Cincinnati Pediat Res Grp, 3333 Burnet Ave, Cincinnati, OH 45229 USA. RI Khoury, Jane/O-2068-2015 NR 18 TC 6 Z9 7 U1 0 U2 2 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 JUL PY 2006 VL 45 IS 6 BP 518 EP 524 DI 10.1177/0009922806290567 PG 7 WC Pediatrics SC Pediatrics GA 064OT UT WOS:000239099700004 PM 16893856 ER PT J AU Quinn, MT Ammons, MCB Deleo, FR AF Quinn, Mark T. Ammons, Mary Cloud B. Deleo, Frank R. TI The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction SO CLINICAL SCIENCE LA English DT Review DE cellular homoeostasis; host defence; NADPH oxidase; pathogenesis; phagocyte; reactive oxygen species (ROS); superoxide anion ID CHRONIC GRANULOMATOUS-DISEASE; VASCULAR SMOOTH-MUSCLE; DINUCLEOTIDE PHOSPHATE OXIDASE; INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; OXYGEN SPECIES PRODUCTION; NEUTROPHIL CYTOCHROME-B; GASTRIC-MUCOSAL CELLS; INDUCED LIVER-DISEASE; OXIDATIVE DNA-DAMAGE AB The NADPH oxidase was originally identified as a key component of human innate host defence. In phagocytes, this enzyme complex is activated to produce superoxide anion and other secondarily derived ROS (reactive oxygen species), which promote killing of invading micro-organisms. However, it is now well-established that NADPH oxidase and related enzymes also participate in important cellular processes not directly related to host defence, including signal transduction. cell proliferation and apoptosis. These enzymes are present in essentially every organ system in the body and contribute to a multitude of physiological events. Although essential for human health, excess NADPH-oxidase-generated ROS can promote numerous pathological conditions. Herein, we summarize our current understanding of NADPH oxidases and provide an overview of how they contribute to specific human diseases. C1 Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Quinn, MT (reprint author), Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA. EM mquinn@montana.edu RI Bell, Tiffany/F-4403-2010; OI DeLeo, Frank/0000-0003-3150-2516; Ammons, Mary Cloud/0000-0002-9717-0844 FU Intramural NIH HHS; NCRR NIH HHS [P01 RR020185]; NIAMS NIH HHS [R01 AR42426] NR 239 TC 105 Z9 111 U1 2 U2 11 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD JUL PY 2006 VL 111 IS 1 BP 1 EP 20 DI 10.1042/cs20060059 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 060KV UT WOS:000238802000001 PM 16764554 ER PT J AU Nieman, LK Turner, MLC AF Nieman, Lynnette K. Turner, Maria L. Chanco TI Addison's disease SO CLINICS IN DERMATOLOGY LA English DT Article ID ADRENAL INSUFFICIENCY; AUTOIMMUNE-DISEASE; SUPPLEMENTATION; PLASMA AB Addison's disease, or primary adrenal insufficiency, results in glucocorticoid and mineralocorticoid deficiency. Orthostatic hypotension, fever, and hypoglycemia characterize acute adrenal crisis, whereas chronic primary adrenal insufficiency presents with a more insidious history of malaise, anorexia, diarrhea, weight loss, joint, and back pain. The cutaneous manifestations include darkening of the skin especially in sun-exposed areas and hyperpigmentation of the palmar creases, frictional surfaces, vermilion border, recent scars, genital skin, and oral mucosa. Measurement of basal plasma cortisol is an insensitive screening test. Synthetic adrenocorticotropin 1-24 at a dose of 250 mu g works well as a dynamic test. Elevated plasma levels of adrenocorticotropin and renin confirm the diagnosis. Treatment involves replacement of the deficient hormones. Published by Elsevier Inc. C1 NICHHD, Reprod & Biol Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, Reprod & Biol Med Branch, NIH, Bethesda, MD 20892 USA. EM niemanl@nih.gov FU Intramural NIH HHS NR 22 TC 39 Z9 40 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JUL-AUG PY 2006 VL 24 IS 4 BP 276 EP 280 DI 10.1016/j.clindermatol.2006.04.006 PG 5 WC Dermatology SC Dermatology GA 066BG UT WOS:000239203800007 PM 16828409 ER PT J AU Huang, BJ Grant, BF Dawson, DA Stinson, FS Chou, SP Saha, TD Goldstein, RB Smith, SM Ruan, WJ Pickering, RP AF Huang, BJ Grant, BF Dawson, DA Stinson, FS Chou, SP Saha, TD Goldstein, RB Smith, SM Ruan, WJ Pickering, RP TI Race-ethnicity and the prevalence and co-occurrence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, alcohol and drug use disorders and Axis I and II disorders: United States, 2001 to 2002 SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; DSM-IV; PERSONALITY-DISORDERS; PSYCHIATRIC-DISORDERS; ICD-10 ALCOHOL; ANXIETY DISORDERS; ABUSE DIAGNOSES; HEAVY DRINKERS AB The objective of this study was to compare the current prevalence and co-occurrence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, alcohol and drug use disorders and mood, anxiety, and personality disorders among whites, blacks, Native Americans, Asians, and Hispanics in a large representative sample of the US population. Striking mental health disparities were observed in the prevalence of psychiatric disorders, especially among Native Americans. Disparities in psychiatric comorbidity differed from those associated with prevalence. Most significantly, the association between alcohol disorders and personality disorders was significantly greater among Asians relative to whites, blacks, and Native Americans, despite lower prevalences of these disorders among Asians. Taken together, the results of this study highlight the need of future studies that help unravel the risk factors underlying the disparities in both prevalence and comorbidity of psychiatric disorders observed among race-ethnic groups in the United States. (c) 2006 Elsevier Inc. All rights reserved. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Huang, BJ (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM HuangBo@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 NR 41 TC 4 Z9 4 U1 4 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2006 VL 47 IS 4 BP 254 EP 259 DI 10.1016/j.comppsych.2005.11.001 PG 6 WC Psychiatry SC Psychiatry GA 058BL UT WOS:000238639000003 ER PT J AU Goldstein, RB Grant, BF Huang, BJ Smith, SM Stinson, FS Dawson, DA Chou, SP AF Goldstein, RB Grant, BF Huang, BJ Smith, SM Stinson, FS Dawson, DA Chou, SP TI Lack of remorse in antisocial personality disorder: sociodemographic correlates, symptomatic presentation, and comorbidity with Axis I and Axis II disorders in the National Epidemiologic Survey on Alcohol and Related Conditions SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID SUBSTANCE USE DISORDERS; DRUG-USE DISORDERS; CONDUCT DISORDER; PSYCHOPATHY CHECKLIST; ANXIETY DISORDERS; UNITED-STATES; PSYCHIATRIC-DIAGNOSIS; OPPOSITIONAL DEFIANT; PREDICTIVE-VALIDITY; DEPENDENT PATIENTS AB Objective: The purpose of this study was to compare sociodemographic and family history correlates, symptomatic presentation, and comorbidity with Axis I and Axis II disorders, in an epidemiologic sample of adults with DSM-IV antisocial personality disorder (ASPD) who lacked, vs those who did not lack, remorse. Methods: This study is based on a nationally representative sample of adults. Lifetime prevalences of each ASPD diagnostic criterion and each comorbid mood, anxiety, substance use, and personality disorder were estimated. Logistic regression was used to examine associations of lack of remorse with ASPD symptom patterns and comorbid disorders. Diagnoses were made using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Results: Among the 1422 respondents with ASPD, 728 (51%) lacked remorse. Respondents who lacked remorse were younger and more often reported a family history of drug problems than those who did not. More often than remorse-positive respondents, those who were remorse-negative met diagnostic criteria involving violence against persons and less often met criteria involving offenses against property. Remorse was not associated with cruelty to animals, nor with most nonviolent antisocial behaviors. Remorse-negative respondents endorsed more total lifetime violent behaviors than those who were remorse-positive. Lack of remorse was not associated with any lifetime comorbid Axis I or Axis II disorder. Patterns of findings were generally similar between men and women. Conclusions: Lack of remorse appears to identify at best a modestly more symptomatically severe and violent form of ASPD in nonclinical populations. (c) 2006 Elsevier Inc. All rights reserved. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 NR 64 TC 2 Z9 2 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2006 VL 47 IS 4 BP 291 EP 299 DI 10.1016/j.comppsych.2005.11.002 PG 9 WC Psychiatry SC Psychiatry GA 058BL UT WOS:000238639000009 ER PT J AU Zhang, SM Bodenreider, O AF Zhang, Songmao Bodenreider, Olivier TI Law and order: Assessing and enforcing compliance with ontological modeling principles in the Foundational Model of Anatomy SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE ontology; anatomy; Foundational Model of Anatomy (FMA); consistency; hierarchical circular relations; dependence; relations equivalence ID REPRESENTATION; KNOWLEDGE; TAXONOMY AB The objective of this study is to provide an operational definition of principles with which well-formed ontologies should comply. We define 15 such principles, related to classification (e.g., no hierarchical cycles are allowed; concepts have a reasonable number of children), incompatible relationships (e.g., two concepts cannot stand both in a taxonomic and partitive relation), dependence among concepts, and the co-dependence of equivalent sets of relations. Implicit relations-embedded in concept names or inferred from a combination of explicit relations-are used in this process in addition to the relations explicitly represented. As a case study, we investigate the degree to which the Foundational Model of Anatomy (FMA)-a large ontology of anatomy-complies with these 15 principles. The FMA succeeds in complying with all the principles: totally with one and mostly with the others. Reasons for non-compliance are analyzed and suggestions are made for implementing effective enforcement mechanisms in ontology development environments. The limitations of this study are also discussed. Published by Elsevier Ltd. C1 US Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Bodenreider, O (reprint author), US Natl Lib Med, NIH, Bethesda, MD 20894 USA. EM smzhang@math.ac.cn; olivier@nlm.nih.gov RI Smith, Barry/A-9525-2011 OI Smith, Barry/0000-0003-1384-116X FU Intramural NIH HHS [Z99 LM999999] NR 27 TC 11 Z9 11 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JUL-AUG PY 2006 VL 36 IS 7-8 BP 674 EP 693 DI 10.1016/j.compbiomed.2005.04.007 PG 20 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 059LW UT WOS:000238735300002 PM 16144698 ER PT J AU Moorhead, R Johnson, C Munzner, T Pfister, H Rheingans, P Yoo, TS AF Moorhead, R Johnson, C Munzner, T Pfister, H Rheingans, P Yoo, TS TI Visualization research challenges - A report summary SO COMPUTING IN SCIENCE & ENGINEERING LA English DT Editorial Material C1 Mississippi State Univ, Mississippi State, MS 39762 USA. Univ Utah, SCI, Salt Lake City, UT 84112 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Mitsubishi Elect Res Labs, Cambridge, England. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. Natl Lib Med, Off High Performance Comp & Commun, Program BD Informat, NIH, Bethesda, MD 20894 USA. RP Moorhead, R (reprint author), Mississippi State Univ, Mississippi State, MS 39762 USA. EM rjm@hpc.msstate.edu; crj@sci.utah.edu; tmm@cs.ubc.ca; pfister@merl.com; rheingan@cs.umbc.edu; yoo@nlm.nih.gov NR 11 TC 2 Z9 2 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1521-9615 J9 COMPUT SCI ENG JI Comput. Sci. Eng. PD JUL-AUG PY 2006 VL 8 IS 4 BP 66 EP 73 DI 10.1109/MCSE.2006.77 PG 8 WC Computer Science, Interdisciplinary Applications SC Computer Science GA 056RT UT WOS:000238543500010 ER PT J AU Djalilian, AR Nagineni, CN Mahesh, SP Smith, JA Nussenblatt, RB Hooks, JJ AF Djalilian, Ali R. Nagineni, Chandrasekharam N. Mahesh, Sankanaranayana P. Smith, Janine A. Nussenblatt, Robert B. Hooks, John J. TI Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin SO CORNEA LA English DT Article DE cornea; inflammation; cytokines; chemokines; dexamethasone; cyclosporin ID GENE-EXPRESSION; EPITHELIAL-CELLS; TRANSPLANT REJECTION; RECEPTOR ANTAGONIST; EYE; KERATOCYTES; KERATITIS; ALPHA; BETA; IL-8 AB Purpose: To evaluate the modulatory effects of anti-inflammatory agents, dexamethasone (Dex) and cyclosporin A (CsA), on the production of cytokines and chemokines by human corneal cells in vitro following stimulation by the pro-inflammatory cytokine after interleukin 1 beta (IL-1 beta). Methods: A human corneal epithelial (HCE) cell line and human corneal fibroblasts (HCFs) were stimulated in culture with IL-10 and treated with Dex or CsA. The gene expression for selected cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The secretion of cytokines and chemokines was measured by enzyme-linked immunosorbent assay. Results: IL-1 beta enhanced the mRNA and/or protein levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, and monocyte chemotactic protein (MCP)-1 in HCE and IL-6, IL-8, MCP-3, and regulated on T-cell activation expressed secreted (RANTES) in HCFs. Treatment with CsA did not inhibit cytokine production in either HCE or HCFs. In contrast, Dex treatment inhibited the IL-1 beta-induced production of GM-CSF, IL-6, IL-8, MCP-3, and RANTES, but not MCP-1. Conclusion: These results show that Dex, but not CsA, has direct immunosuppressive effects on the resident corneal cells, HCE and HCFs. This suggests that the clinically observed immunosuppressive effects of topical CsA are mediated primarily through the immune cells. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Djalilian, AR (reprint author), Univ Illinois, Dept Ophthalmol, EEI, Room 3-164, Chicago, IL 60612 USA. EM adjalili@uic.edu FU Intramural NIH HHS NR 33 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2006 VL 25 IS 6 BP 709 EP 714 DI 10.1097/01.ico.0000208815.02120.90 PG 6 WC Ophthalmology SC Ophthalmology GA 091HF UT WOS:000241017100015 PM 17077666 ER PT J AU Klein, HG AF Klein, HG TI Blood avoidance for the critically ill: Another blow to liberalism? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE transfusion; transfusion trigger; blood; red cells ID TRANSFUSION PRACTICE; ANEMIA; HUMANS; TRIAL C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 19 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2006 VL 34 IS 7 BP 2013 EP 2014 DI 10.1097/01.CCM.0000224226.45049.20 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 058BN UT WOS:000238639300024 PM 16801868 ER PT J AU O'Grady, NP Salgado, CD Farr, BM AF O'Grady, NP Salgado, CD Farr, BM TI Selective decontamination of the digestive tract does not increase resistance in critically ill patients: Evidence from randomized controlled trials - Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID VENTILATOR-ASSOCIATED PNEUMONIA; MOUSE GASTROINTESTINAL-TRACT; VANCOMYCIN-RESISTANT; STAPHYLOCOCCUS-AUREUS; ENTEROCOCCUS-FAECIUM; RISK-FACTORS; INFECTION; COLONIZATION; PROPHYLAXIS; BACTEREMIA C1 NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Virginia, Charlottesville, VA USA. RP O'Grady, NP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2006 VL 34 IS 7 BP 2029 EP 2030 DI 10.1097/01.CCM.0000226401.19289.A2 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 058BN UT WOS:000238639300036 ER PT J AU Miyazaki, T Tsai, HF Bennett, JE AF Miyazaki, T Tsai, HF Bennett, JE TI Kre29p is a novel nuclear protein involved in DNA repair and mitotic fidelity in Candida glabrata SO CURRENT GENETICS LA English DT Article DE DNA damage; cell cycle; mitosis; nucleus; plasmid partitioning ID SACCHAROMYCES-CEREVISIAE GENOME; ANTIFUNGAL SUSCEPTIBILITY; CHROMOSOME SEGREGATION; SMC PROTEINS; BUDDING YEAST; ALBICANS; COMPLEX; DAMAGE; GENE; CHECKPOINT AB Candida glabrata KRE29 is an ortholog of Saccharomyces cerevisiae KRE29. S. cerevisiae Kre29p has been identified by affinity purification as a subunit of the Smc5-Smc6 complex, which is required for DNA repair and chromosome segregation. However, mutant phenotypes of S. cerevisiae KRE29 have not been well characterized and none of its orthologs' functions has been reported. Here we report phenotypic characteristics of a C. glabrata kre29 deletant. The absence of C. glabrata Kre29p resulted in decreased viability, exhibiting cell cycle arrest between late S-phase and metaphase even under normal growth conditions, and also caused an increase of plasmid loss rate, implying that Kre29p is required for mitotic chromosome transmission fidelity. The deletant showed increased sensitivity to high temperature as well as to DNA damaging agents including UV, gamma ray, 4-nitroquinoline-1-oxide and methyl methanesulfonate, and the phenotypes were restored in the KRE29 reintegrant. Consistent with the Delta kre29 phenotypes, a Kre29p-GFP fusion protein was located in the nucleus. Furthermore, Kre29p-GFP became concentrated and formed distinct foci after exposure to 4-nitroquinoline-1-oxide. These results suggest the involvement of C. glabrata Kre29p in DNA repair. To our knowledge, this is the first report addressing a cellular protein involved in DNA repair in C. glabrata. C1 NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Clin Ctr Room 11C304, Bethesda, MD 20892 USA. EM jbennett@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 3 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0172-8083 J9 CURR GENET JI Curr. Genet. PD JUL PY 2006 VL 50 IS 1 BP 11 EP 22 DI 10.1007/s00294-006-0072-3 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 053PM UT WOS:000238317100002 PM 16775745 ER PT J AU Marsh, JW Ross, TM AF Marsh, Jon W. Ross, Ted M. TI Focus on NeuroAIDS - Preface SO CURRENT HIV RESEARCH LA English DT Editorial Material C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA. RP Marsh, JW (reprint author), NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. EM marshj@mail.nih.gov; RossT@dom.pitt.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2006 VL 4 IS 3 BP 243 EP 243 DI 10.2174/157016206777709465 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 063LY UT WOS:000239020900001 ER PT J AU Nunn, MF AF Nunn, Michael F. TI NeuroAIDS: A neuroscience problem with global impact SO CURRENT HIV RESEARCH LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV DEMENTIA; INFECTION; BRAIN; PROTEIN; MODEL C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Nunn, MF (reprint author), NINDS, NIH, 6001 Execut Blvd,Room 2115, Bethesda, MD 20892 USA. EM nunnm@ninds.nih.gov NR 18 TC 2 Z9 3 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2006 VL 4 IS 3 BP 245 EP 247 DI 10.2174/157016206777709483 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 063LY UT WOS:000239020900002 PM 16842077 ER PT J AU Schwartz, L Major, EO AF Schwartz, Lynnae Major, Eugene O. TI Neural progenitors and HIV-1-associated central nervous system disease in adults and children SO CURRENT HIV RESEARCH LA English DT Review DE HIV-1; progenitor; neuropathogenesis; neuroAIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR CXCR4; IMMUNE-DEFICIENCY SYNDROME; BINDING PROTEIN MUSASHI-1; NEWLY GENERATED NEURONS; STEM-CELLS; HIV-1 INFECTION; HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; HUMAN BRAIN AB The human immunodeficiency virus type 1 (HIV-1) is a neurotrophic lentivirus that enters and infects the central nervous system (CNS) of adults and children, giving rise to the clinical syndromes of AIDS-dementia complex (ADC) in adults and HIV-1-associated progressive encephalopathy (PE) in pediatric patients. The clinical presentation and progression of neuroAIDS in the developing brain of children is distinct from that seen in adult patients. Neuroimaging, and upon autopsy, neuropathological findings corresponding to clinical disease in pediatric patients include impaired brain growth, reactive gliosis, myelin pallor, calcifications of the basal ganglia, cortical and cerebral atrophy with neuronal loss and ventricular enlargement, and abnormalities of cerebral vasculature. Although there is some overlap with neuropathologic findings in adult patients, ADC in adults is more typically a late development, often complicated by opportunistic infections of the CNS. The neuropathogenesis of ADC and PE is incompletely understood. One population of CNS cells critical for brain development and response to injury and inflammation are neural progenitors cells, and it has therefore been suggested that these cells may be involved in the neuropathogenesis of ADC, and especially PE. This review examines the neurobiology of neural progenitor cells and the possibility that HIV-1 infection of neural progenitors, exposure of neural progenitors to virus, viral products, or progenitor exposure to HIV-1 associated neuroinflammatory substances and neurotoxins might contribute to the neuropathogenesis of AIDS in adults and children. That some of the clinical differences between ADC and PE might, in part, be explained by differences in neural progenitor involvement will also be considered. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Schwartz, L (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Room 3B14 Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM schwartl@ninds.nih.gov NR 134 TC 30 Z9 31 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2006 VL 4 IS 3 BP 319 EP 327 DI 10.2174/157016206777709438 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 063LY UT WOS:000239020900009 PM 16842084 ER PT J AU Schito, ML Soloff, AC Slovitz, D Trichel, A Inman, JK Appella, E Turpin, JA Barratt-Boyes, SM AF Schito, Marco L. Soloff, Adam C. Slovitz, Danielle Trichel, Anita Inman, John K. Appella, Ettore Turpin, Jim A. Barratt-Boyes, Simon M. TI Preclinical evaluation of a zinc finger inhibitor targeting lentivirus nucleocapsid protein in SIV-infected monkeys SO CURRENT HIV RESEARCH LA English DT Article DE HIV/SIV; NCp7; zinc finger inhibitor; primate ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; VIRAL-RNA; IN-VITRO; NONINFECTIOUS VIRUS; STRAND TRANSFER; HIV-1; DNA; THERAPY; NCP7 AB There is a continued need to develop inexpensive and effective drugs specific for novel targets of human immunodeficiency virus type 1 (HIV-1). The HIV-1 nucleocapsid p7 (NCp7) protein plays a critical role in early and late stages of the virus life cycle and possesses two highly conserved retroviral zinc fingers that are essential for its function. We have previously shown that zinc finger inhibitors (ZFI) based on the S-acyl 2-mercaptobenzamide thioester (SAMT) chemotype specifically target HIV NCp7 and are effective at reducing levels of infectious virus in an HIV-1-transgenic mouse model. Here, we did an initial proof-of-concept study to test the potential of a lead SAMT compound to reduce virus infectivity in the simian immunodeficiency virus (SIV) nonhuman primate model. SAMT-19 had potent antiviral and virucidal effects against the primary pathogenic isolate SIV/DeltaB670 and was non-cytotoxic in vitro. Cynomolgus macaques were infected intrarectally with SIV/DeltaB670 and treated with a low dose of SAMT-19 by continuous infusion from day 8 to day 28 post infection. Monkeys in the treatment group had significantly lower levels of infectious virus in peripheral blood mononuclear cells during the course of therapy as compared to monkeys in the control group, although therapy had no demonstrable effect on virus load. SAMT-19 therapy did not alter liver, kidney or immunologic function and was well tolerated by all treated monkeys. These data demonstrate that SAMT-19 is safe and virucidal in the nonhuman primate model. Further studies directed at optimizing SAMT bioavailability and pharmacokinetics likely will result in enhanced therapeutic efficacy of this promising HIV therapeutic. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hnery M Jackson Fdn, Bethesda, MD 20892 USA. RP Schito, ML (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2140, Bethesda, MD 20892 USA. EM schitom@mail.nih.gov OI Barratt Boyes, Simon/0000-0002-8869-4945 FU Intramural NIH HHS NR 40 TC 12 Z9 15 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2006 VL 4 IS 3 BP 379 EP 386 DI 10.2174/157016206777709492 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 063LY UT WOS:000239020900014 PM 16842089 ER PT J AU Hallett, M AF Hallett, Mark TI Psychogenic movement disorders: A crisis for neurology SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Editorial Material ID MEDICALLY UNEXPLAINED SYMPTOMS; PROSPECTIVE COHORT; FREQUENCY; REFERRALS; PERSPECTIVE; OUTPATIENT; DISABILITY; MYOCLONUS; SEIZURES; EPILEPSY C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 32 TC 34 Z9 34 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD JUL PY 2006 VL 6 IS 4 BP 269 EP 271 DI 10.1007/s11910-006-0015-x PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 150GH UT WOS:000245203100001 PM 16822346 ER PT J AU Mattapallil, JJ Roederer, M AF Mattapallil, Joseph J. Roederer, Mario TI HIV vaccines: can mucosal CD4 T cells be protected? SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE acute infection; blood; CCR5; CD4 T cells; gut; HIV; immunodeficiency; intestine; mucosa; rhesus; SIV; T cell AB Purpose of review The aim of this article is to understand the significance of protecting the mucosal tissue compartment during acute HIV infection, and to describe the current efforts towards this goal. Recent findings The mucosa is the primary route of HIV transmission, and serves as a major site for viral dissemination leading to a massive destruction of the memory CD4 T cell compartment. This destruction is mediated as a consequence of direct viral infection and occurs in all the tissues of the body suggesting that once infection explodes out of the mucosal tissues memory CD4 T cells at all other sites are very rapidly infected and destroyed. Summary The enrichment of highly susceptible CD4 targets in mucosal tissues suggests that the immune system will need to be in a state of high alert to contain infection once HIV crosses the mucosal barrier. This will require the generation and maintenance of strong vaccine-induced neutralizing antibodies and CD8 T cell responses in mucosal tissues. Given the challenges of inducing neutralizing antibodies, current efforts are focused on developing a T cell based vaccine that can contain the spread of HIV infection. Developing a T cell based vaccine is hampered by the lack of any predictive correlates of protection. In the absence of such correlates, protection can be measured by the extent to which mucosal CD4 T cells are preserved. Preservation of mucosal CD4 T cells will have a significant impact on disease course and long-term outcome. C1 [Mattapallil, Joseph J.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mattapallil, JJ (reprint author), 40 Convent Dr,Room 5610, Bethesda, MD 20895 USA. EM jmattapallil@mail.nih.gov NR 60 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JUL PY 2006 VL 1 IS 4 BP 272 EP 276 DI 10.1097/01.COH.0000232341.77790.33 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NO UT WOS:000208417300002 PM 19372821 ER PT J AU Fenton, WS Stover, ES AF Fenton, Wayne S. Stover, Ellen S. TI Mood disorders: cardiovascular and diabetes comorbidity SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE cardiovascular disease; collaborative care; comorbidity; depression; diabetes ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSION; GLYCEMIC CONTROL; MYOCARDIAL-INFARCTION; MEDICATION ADHERENCE; RANDOMIZED-TRIAL; MEDICALLY ILL; PRIMARY-CARE; DOUBLE-BLIND AB Purpose of review: Depression is often associated with medical comorbidity. New research quantifies patterns of mood disorder in illnesses such as cardiovascular disease and diabetes, evaluates the prognostic significance of mood symptoms, and seeks to identify common mechanisms for both mood and medical disease. This review provides recent findings on comorbidity, summarizes mechanistic hypotheses, and outlines developments in treatment and services. Recent findings: Depression occurs in up to one-quarter of patients with cardiovascular disease and diabetes. Depressed patients with heart disease have poorer medical outcomes including increased risk of reinfarction and all-cause mortality. Patients with diabetes and depression have poorer glycemic control, more diabetes symptoms, and greater all-cause mortality. Depression is associated with both biological (hypothalamic-pituitary-adrenal axis dysregulation) and psychosocial processes (adherence, poorer diet, and exercise) that may mediate adverse medical outcomes. Antidepressant treatments are effective in treating depression in medically ill patients, but their impact on medical outcomes remains to be quantified. Summary: Depression, cardiovascular disease, and diabetes are among the most common chronic illnesses affecting an aging population. Depression is treatable in patients with medical illnesses, and collaborative care models can yield better detection and depression treatment in primary care settings in which most patients with depression are seen. C1 NIMH, NIH, DHHS, Bethesda, MD 20892 USA. RP Fenton, WS (reprint author), NIMH, NIH, DHHS, 6001 Execut Blvd,MSC 9621, Bethesda, MD 20892 USA. EM wfenton@mail.nih.gov NR 59 TC 49 Z9 51 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JUL PY 2006 VL 19 IS 4 BP 421 EP 427 DI 10.1097/01.yco.0000228765.33356.9f PG 7 WC Psychiatry SC Psychiatry GA 060KM UT WOS:000238801100015 PM 16721175 ER PT J AU Ovchinnikov, DA Selever, J Wang, Y Chen, YT Mishina, Y Martin, JF Behringer, RR AF Ovchinnikov, Dmitry A. Selever, Jennifer Wang, Ying Chen, You-Tzung Mishina, Yuji Martin, James F. Behringer, Richard R. TI BMP receptor type IA in limb bud mesenchyrne regulates distal outgrowth and patterning SO DEVELOPMENTAL BIOLOGY LA English DT Article DE bone morphogenetic protein receptor; limb development; pattern formation; conditional knockout; Prx1 ID BONE MORPHOGENETIC PROTEINS; APICAL ECTODERMAL RIDGE; PROGRAMMED CELL-DEATH; DEVELOPING CHICK LIMB; GROWTH-FACTOR-BETA; VERTEBRATE LIMB; SONIC-HEDGEHOG; GENE-EXPRESSION; MOUSE LIMB; POLARIZING ACTIVITY AB The mesenchyme of the developing vertebrate limb responds to inductive signals, giving rise to skeletal elements that define limb shape and size. Several signals emanate from the limb ectoderm and in particular from the specialized epithelium of the apical ectodermal ridge (AER), including three members of the bone morphogenetic protein (BMP) family of signaling molecules, BMP2, BMP4 and BMP7. Using the Cre/loxP system in mice, we rendered limb bud mesenchyme insensitive to BMP signals through the type I receptor, BMPR-IA. Conditional mutants had shortened limbs and almost complete agenesis of the autopod because of reduced cell proliferation. Reduced expression of downstream BMP signaling targets, Msx1, Msx2 and gremlin in the distal mesenchyme (progress zone) correlated with decreased levels of cyclin D1 and Wnt5a. Ectopic anterior activation of sonic hedgehog (SHH) signaling and Hox expression revealed alterations in anterior-posterior (AP) patterning. Abnormal localization of Lmx1b-expressing cells in the ventral mesenchyme, along with histological alterations and an abnormal melanization pattern of the limb, indicate altered dorsal-ventral (DV) boundaries. These findings suggest that signaling through BMPR-IA in limb mesenchyme is essential for distal outgrowth and also influences AP and DV patterning. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Texas A&M Univ, Inst Biosci & Technol, Houston, TX 77030 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Behringer, RR (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM rrb@mdanderson.org RI Ovchinnikov, Dmitry/J-7963-2014 OI Ovchinnikov, Dmitry/0000-0001-9603-8385 FU NCI NIH HHS [CA16672]; NIAMS NIH HHS [AR42919] NR 75 TC 59 Z9 61 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 BP 103 EP 115 DI 10.1016/j.ydbio.2006.03.013 PG 13 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200009 PM 16630606 ER PT J AU Rangarajan, J Luo, T Sargent, TD AF Rangarajan, Janaki Luo, Ting Sargent, Thomas D. TI PCNS: A novel protocadherin required for cranial neural crest migration and somite morphogenesis in Xenopus SO DEVELOPMENTAL BIOLOGY LA English DT Article DE somitogenesis; cadherin; cell adhesion; epitheliomesenchymal transition ID TRANSCRIPTION FACTOR AP-2; CNR/PCDH-ALPHA GENES; PARAXIAL PROTOCADHERIN; CELL MOVEMENTS; CADHERIN SUPERFAMILY; CRANIOFACIAL DEVELOPMENT; CONVERGENT EXTENSION; MOLECULAR-MECHANISMS; GENOMIC ORGANIZATION; PRESOMITIC MESODERM AB Protocadherins (Pcdhs), a major subfamily of cadherins, play an important role in specific intercellular interactions in development. These molecules are characterized by their unique extracellular domain (EC) with more than 5 cadherin-like repeats, a transmembrane domain (TM) and a variable cytoplasmic domain. PCNS (Protocadherin in Neural crest and Somites), a novel Pcdh in Xenopus, is initially expressed in the mesoderm during gastrulation, followed by expression in the cranial neural crest (CNC) and somites. PCNS has 65% amino acid identity to Xenopus paraxial protocadherin (PAPC) and 42-49% amino acid identity to Pcdh 8 in human, mouse, and zebrafish genomes. Overexpression of PCNS resulted in gastrulation failure but conferred little if any specific adhesion on ectodermal cells. Loss of function accomplished independently with two non-overlapping antisense morpholino oligonucleotides resulted in failure of CNC migration, leading to severe defects in the craniofacial skeleton. Somites and axial muscles also failed to undergo normal morphogenesis in these embryos. Thus, PCNS has essential functions in these two important developmental processes in Xenopus. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 94 TC 22 Z9 22 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 BP 206 EP 218 DI 10.1016/j.ydbio.2006.03.025 PG 13 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200017 PM 16674935 ER PT J AU Spradling, A Ohlstein, B Buszczak, M Nystul, T Morris, L Decotto, E AF Spradling, Allan Ohlstein, Benjamin Buszczak, Michael Nystul, Todd Morris, Lucy Decotto, Eva TI Multiple types of niche control stem cells in drosophila adults SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Carnegie Inst, HHMI, Baltimore, MD 21218 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 19 BP 329 EP 329 DI 10.1016/j.ydbio.2006.04.029 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200043 ER PT J AU Wolff, GS Chiang, PJ Smith, SS Romero, R Armant, DR AF Wolff, Garen S. Chiang, Po J. Smith, Susan S. Romero, Roberto Armant, D. Randall TI Contribution of aberrant placentation to fetal alcohol syndrome SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Wayne State Univ, Dept OB GYN, Detroit, MI USA. Univ Wisconsin, Dept Nutrit Sci, Madison, WI USA. NICHHD, NIH, DHHS, Perinatol Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 67 BP 352 EP 352 DI 10.1016/j.ydbio.2006.04.084 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200090 ER PT J AU Daar, IO Lee, HS Bong, YS Moore, KB Soria, K Moody, SA AF Daar, Ira O. Lee, Hyun-Shik Bong, Yong-Sik Moore, Kathryn B. Soria, Kathleen Moody, Sally A. TI Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Natl Canc Inst, Lab Prot Dynam & Signaling, Frederick, MD USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT USA. George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC USA. OI Moody, Sally/0000-0003-4192-1087 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 103 BP 365 EP 365 DI 10.1016/j.ydbio.2006.04.123 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200126 ER PT J AU Brody, T Rasband, W Baler, K Kuzin, A Odenwald, WF AF Brody, Thomas Rasband, Wayne Baler, Kevin Kuzin, Alexander Odenwald, Ward F. TI Decoding cis-regulatory sequences involved in coordinate gene expression in Drosophila SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. NIMH, IRP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 127 BP 374 EP 374 DI 10.1016/j.ydbio.2006.04.148 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200150 ER PT J AU Kuzin, A Kundu, M Brody, T Odenwald, WF AF Kuzin, Alexander Kundu, Mukta Brody, Thomas Odenwald, Ward F. TI Transcriptional and post-transcriptional regulation of the nerfin-1 expression during Drosophila neurogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 129 BP 374 EP 375 DI 10.1016/j.ydbio.2006.04.150 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200152 ER PT J AU Buckley, MS Ullah, Z Williams, GL Arnosti, DN Henry, RW AF Buckley, Martin S. Ullah, Zakir Williams, Geoffrey L. Arnosti, David N. Henry, R. William TI Regulation of retinoblastoma protein stability and function by the COP signalosome SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Michigan State Univ, E Lansing, MI 48824 USA. NIH, Bethesda, MD 20892 USA. Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 133 BP 376 EP 376 DI 10.1016/j.ydbio.2006.04.154 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200156 ER PT J AU Feldman, B Costa, J AF Feldman, Benjamin Costa, Justin TI A reverse-genetic screen identifying RhoGEF genes that are essential for zebrafish epiboly SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 186 BP 394 EP 395 DI 10.1016/j.ydbio.2006.04.209 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200209 ER PT J AU Komatsu, Y Fukuda, T Scott, G Kamiya, N Yamamura, K Mishina, Y AF Komatsu, Yoshihiro Fukuda, Tomokazu Scott, Gregory Kamiya, Nobuhiro Yamamura, Ken-ichi Mishina, Yuji TI Enhanced BMP signaling through a type I BMP receptor ALK2 shows ectopic cartilage formation in mouse craniofacial portion SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA. Kumamoto Univ, Inst Mol Embryol & Genet, Kumamoto, Japan. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 200 BP 399 EP 399 DI 10.1016/j.ydbio.2006.04.223 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200223 ER PT J AU Feldman, B Boorech, JL Noushmehr, H Kirby, M Elkahloun, AG AF Feldman, Benjamin Boorech, Jamie L. Noushmehr, Houtan Kirby, Martha Elkahloun, Abdel G. TI FACS-assisted microdissection of photolabeled cells to identify germ layer-specific genes SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NHGRI, NIH, Bethesda, MD 20892 USA. RI Noushmehr, Houtan/C-9692-2013 OI Noushmehr, Houtan/0000-0003-4051-8114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 242 BP 412 EP 413 DI 10.1016/j.ydbio.2006.04.267 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200265 ER PT J AU Armant, DR Kilburn, BA Chiang, PJ Petkova, A Romero, R Leach, RE AF Armant, D. Randall Kilburn, Brian A. Chiang, Po J. Petkova, Anelia Romero, Roberto Leach, Richard E. TI HBEGF prevents trophoblast apoptosis due to reoxygenation injury during placentation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Wayne State Univ, Dept Ob Gyn, Detroit, MI USA. NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Illinois, Dept Ob Gyn, Chicago, IL USA. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 283 BP 426 EP 426 DI 10.1016/j.ydbio.2006.04.311 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200304 ER PT J AU Keller, MJ Chitnis, AB AF Keller, Michael J. Chitnis, Ajay B. TI Her9-dependent regulation of neurogenesis by Zic family proteins SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 326 BP 441 EP 441 DI 10.1016/j.ydbio.2006.04.356 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200345 ER PT J AU Feldman, B Pei, WH Williams, H Clark, M Stemple, DL AF Feldman, Benjamin Pei, Wuhong Williams, Huw Clark, Matthew Stemple, Derek L. TI Squint protects early embryos from temperature-induced dysmorphology SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NHGRI, NIH, Bethesda, MD 20892 USA. Sanger Inst, Hinxton, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 329 BP 442 EP 442 DI 10.1016/j.ydbio.2006.04.359 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200348 ER PT J AU Castranio, T Mishina, Y AF Castranio, Trisha Mishina, Yuji TI Cephalic neural tube closure requires BMP2 expression SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 346 BP 446 EP 447 DI 10.1016/j.ydbio.2006.04.376 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200363 ER PT J AU Miura, S Davis, S Klingensmith, J Mishina, Y AF Miura, Shigeto Davis, Shannon Klingensmith, John Mishina, Yuji TI BMP signaling in the epiblast is required for proper recruitment of the prospective paraxial mesoderm and development of somites SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 344 BP 446 EP 446 DI 10.1016/j.ydbio.2006.04.374 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200361 ER PT J AU Driver, EC Pryor, SP Hill, P Turner, J Ruther, U Biesecker, LG Griffith, J Kelley, MW AF Driver, E. C. Pryor, S. P. Hill, P. Turner, J. Ruether, U. Biesecker, L. G. Griffith, J. Kelley, M. W. TI GLI3 and Sonic hedgehog regulate hair cell formation and auditory function in mice and humans SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NIDCD, NIH, Bethesda, MD USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. NIDCD, NIH, Rockville, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 377 BP 457 EP 457 DI 10.1016/j.ydbio.2006.04.408 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200394 ER PT J AU Zhu, JJ Nguyen, MT Nakamura, E Mackem, S AF Zhu, Jianjian Nguyen, Minh-Thanh Nakamura, Eiichiro Mackem, Susan TI Morphogen or mitogen - re-evaluating how Sonic Hedgehog functions in the developing limb SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 390 BP 461 EP 462 DI 10.1016/j.ydbio.2006.04.421 PG 2 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200407 ER PT J AU Pajni-Underwood, S Mishina, Y Williams, T Lewandoski, M AF Pajni-Underwood, Sangeeta Mishina, Y. Williams, T. Lewandoski, M. TI BMP signaling is required for limb bud mesenchyme survival SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Developmental-Biology CY JUN 17-21, 2006 CL Ann Arbor, MI SP Soc Dev Biol C1 NCI, NIH, Frederick, MD 21701 USA. NIES, NIH, Res Triangle Pk, NC USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2006 VL 295 IS 1 MA 392 BP 462 EP 462 DI 10.1016/j.ydbio.2006.04.423 PG 1 WC Developmental Biology SC Developmental Biology GA 063DL UT WOS:000238996200409 ER PT J AU Shaw, KM Castranova, DA Pham, VN Kamei, M Kidd, KR Lo, BD Torres-Vasquez, J Ruby, A Weinstein, BM AF Shaw, KM Castranova, DA Pham, VN Kamei, M Kidd, KR Lo, BD Torres-Vasquez, J Ruby, A Weinstein, BM TI fused-somites-like mutants exhibit defects in trunk vessel patterning SO DEVELOPMENTAL DYNAMICS LA English DT Article DE blood vessels; zebrafish; fused somites; beamter; deltaC ID NOTCH PATHWAY; ZEBRAFISH SOMITOGENESIS; VASCULAR DEVELOPMENT; DANIO-RERIO; DIFFERENTIATION; ARTERIAL; GROWTH; SEGMENTATION; OSCILLATOR; EXPRESSION AB We identified four mutants in two distinct loci exhibiting similar trunk vascular patterning defects in an F3 genetic screen for zebrafish vascular mutants. Initial vasculogenesis is not affected in these mutants, with proper specification and differentiation of endothelial cells. However, all four display severe defects in the growth and patterning of angiogenic vessels in the trunk, with ectopic branching and disoriented migration of intersegmental vessels. The four mutants are allelic to previously characterized mutants at the fused-somites (fss) and beamter (bea) loci, and they exhibit comparable defects in trunk somite boundary formation. The fss locus has been shown to correspond to tbx24; we show here that bea mutants are defective in the zebrafish dlC gene. Somitic expression of known vascular guidance factors efnb2a, sema3a1, and sema3a2 is aberrantly patterned in fss and bea mutants, suggesting that the vascular phenotype is due to loss of proper guidance cues provided by these factors. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6B,Room 309,6 Ctr Dr, Bethesda, MD 20892 USA. EM bw96w@nih.gov OI Kamei, Makoto/0000-0002-1438-0783 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL092263] NR 32 TC 15 Z9 15 U1 0 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 JUL PY 2006 VL 235 IS 7 BP 1753 EP 1760 DI 10.1002/dvdy.20814 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 055OD UT WOS:000238459100003 PM 16607654 ER PT J AU Garin, E Lemieux, M Coulombe, Y Robinson, GW Jeannotte, L AF Garin, E Lemieux, M Coulombe, Y Robinson, GW Jeannotte, L TI Stromal Hoxa5 function controls the growth and differentiation of mammary alveolar epithelium SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Hox genes; Hoxa5; mammary gland development; mouse; lactation; proliferation; differentiation ID ESTROGEN-RECEPTOR-BETA; GLAND DEVELOPMENT; PROGESTERONE-RECEPTOR; GENE-EXPRESSION; SECRETORY DIFFERENTIATION; TERMINAL DIFFERENTIATION; KNOCKOUT MICE; BREAST-CANCER; MOUSE EMBRYO; MUTANT MICE AB Recent progress has enlightened the involvement of Hox genes in organogenesis. Several Hox genes are expressed in normal and neoplastic mammary glands. Using Hoxa5 mutant mice, we showed that Hoxa5(-/-) females present nursing defects. Characterization of the Hoxa5(-/-) mammary gland phenotype reveals changes in proliferation and differentiation of the epithelium of nulliparous and pregnant Hoxa5(-/-) females that precede the abnormal secretory activity at parturition. These defects likely underlie the incapacity of Hoxa5(-/-) dams to properly feed their pups. Hoxa5 expression is restricted to the mammary stroma at specific stages of mammary gland development. The loss of Hoxa5 function causes accelerated lobuloalveolar epithelium development, a phenotype that can be rescued upon grafting of mutant mammary epithelium into wild-type fat pads. Conversely, reciprocal grafting experiments demonstrate that Hoxa5(-/-) stroma cannot support normal proliferation of wild-type mammary epithelium. These data establish the essential contribution of Hoxa5 to mammary epithelium instruction by means of mesenchymal-epithelial crosstalk. C1 Univ Laval, Ctr Rech Hotel Dieu Quebec, Ctr Hosp Univ Quebec, Quebec City, PQ G1R 2J6, Canada. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Jeannotte, L (reprint author), Univ Laval, Ctr Rech Hotel Dieu Quebec, Ctr Hosp Univ Quebec, 9 Rue McMahon, Quebec City, PQ G1R 2J6, Canada. EM lucie.jeannotte@crhdq.ulaval.ca RI Robinson, Gertraud/I-2136-2012 NR 57 TC 29 Z9 29 U1 0 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 JUL PY 2006 VL 235 IS 7 BP 1858 EP 1871 DI 10.1002/dvdy.20822 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 055OD UT WOS:000238459100012 PM 16607641 ER PT J AU de Haan, M Wyatt, JS Roth, S Vargha-Khadem, F Gadian, D Mishkin, M AF de Haan, Michelle Wyatt, John S. Roth, Simon Vargha-Khadem, Faraneh Gadian, David Mishkin, Mortimer TI Brain and cognitive-behavioural development after asphyxia at term birth SO DEVELOPMENTAL SCIENCE LA English DT Article ID HYPOXIC-ISCHEMIC ENCEPHALOPATHY; SEVERE PERINATAL ASPHYXIA; NEONATAL ENCEPHALOPATHY; MAGNETIC-RESONANCE; OBSTETRIC COMPLICATIONS; RISK-FACTORS; NEWBORN ENCEPHALOPATHY; INTRAPARTUM ASPHYXIA; HIPPOCAMPAL ATROPHY; ONSET SCHIZOPHRENIA AB Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has been implicated in two different long-term outcomes, cognitive memory impairment and the psychiatric disorder schizophrenia. Factors in addition to the acute episode of asphyxia likely contribute to these specific outcomes, making prediction difficult. Future studies that better document long-term cognitive-behavioural outcome, quantitatively identify patterns of brain injury over development and consider additional variables that may modulate the impact of asphyxia on cognitive and behavioural function will forward the goals of predicting long-term outcome and understanding the mechanisms by which it unfolds. C1 UCL, Dev Cognit Neurosci Unit, Inst Child Hlth, Wolfson Ctr, London WC1N 2AP, England. UCL, Rayne Inst, Dept Paediat, London, England. UCL, Radiol & Phys Unit, Inst Child Hlth, London, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP de Haan, M (reprint author), UCL, Dev Cognit Neurosci Unit, Inst Child Hlth, Wolfson Ctr, Mecklenburgh Sq, London WC1N 2AP, England. EM m.de-haan@ich.ucl.ac.uk RI de Haan, Michelle/C-5070-2008; Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008 FU Medical Research Council [G0300117] NR 82 TC 68 Z9 68 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1363-755X J9 DEVELOPMENTAL SCI JI Dev. Sci. PD JUL PY 2006 VL 9 IS 4 BP 350 EP 358 DI 10.1111/j.1467-7687.2006.00499.x PG 9 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 050CZ UT WOS:000238066400003 PM 16764608 ER PT J AU Schinstine, M Torres-Cabala, C Brosky, K Roth, MJ AF Schinstine, M Torres-Cabala, C Brosky, K Roth, MJ TI Ganglion cyst in a 52-year-old man with metastatic melanoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material C1 NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. RP Schinstine, M (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, 940 SL Young Blvd,BMSB 451, Oklahoma City, OK 73104 USA. EM mschinstine@pol.net NR 0 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUL PY 2006 VL 34 IS 7 BP 485 EP 485 DI 10.1002/dc.20376 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 059DM UT WOS:000238713500007 PM 16783777 ER PT J AU Kumar, S Yan, J Muthumani, K Ramanathan, MP Yoon, H Pavlakis, GN Felber, BK Sidhu, M Boyer, JD Weiner, DB AF Kumar, Sanjeev Yan, Jian Muthumani, Karuppiah Ramanathan, Mathura P. Yoon, Hanna Pavlakis, George N. Felber, Barbara K. Sidhu, Maninder Boyer, Jean D. Weiner, David B. TI Immunogenicity testing of a novel engineered HIV-1 envelope Gp140 DNA vaccine construct SO DNA AND CELL BIOLOGY LA English DT Article ID CELL-SURFACE EXPRESSION; IMMUNE-RESPONSES; CYTOPLASMIC DOMAIN; CODON USAGE; ENDOCYTOSIS MOTIF; CLATHRIN ADAPTER; T-CELLS; VIRUS; GLYCOPROTEIN; ENV AB DNA vaccines expressing the envelope (env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating strong immune responses. In this study, we described the development of a recombinant plasmid DNA (pEK2P-B) expressing an engineered codon-optimized envelope gp140 gene of primary (nonrecombinant) HIV-1 subtype B isolate 6101. Codon usage and RNA optimization of HIV-1 structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo. To further increase the expression, a synthetic IgE leader with kozak sequences were fused into the env gene. The cytoplasmic tail of the gene was also truncated to prevent recycling. The expression of env by the recombinant pEK2P-B was evaluated using T7 coupled transcription/translation. The construct demonstrated high expression of the HIV-1 env gene in eukaryotic cells as demonstrated in transfected 293-T and RD cells. Immunogenicity of pEK2P-B was evaluated in mice using IFN-gamma ELISpot assay, and the construct was found to be highly immunogenic and crossreactive with HIV-1 clade C env peptides. Three immunodominant peptides were also mapped out. Furthermore, by performing a CFSE flow cytometry-based proliferation assay, 2.4 and 1.5% proliferation was observed in CD4(+), CD8(+), and CCR+ memory T cells, respectively. Therefore, this engineered synthetic optimized env DNA vaccine may be useful in DNA vaccine and other studies of HIV-1 immunogenicity. C1 Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Natl Canc Inst, Human Retrovirus Sect, Frederick, MD USA. Natl Canc Inst, Human Retrovirus Pathogenesis Sect, Frederick, MD USA. Wyeth Ayerst Res, Vaccines Discovery, Pearl River, NY USA. RP Weiner, DB (reprint author), Univ Penn, Dept Pathol & Lab Med, 505 Stellar Chance Lab,422 Curie Dr, Philadelphia, PA 19104 USA. EM dbweiner@mail.med.upenn.edu RI Muthumani, Karuppiah/D-1092-2009; Weiner, David/H-8579-2014 NR 42 TC 15 Z9 15 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUL PY 2006 VL 25 IS 7 BP 383 EP 392 DI 10.1089/dna.2006.25.383 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 068QR UT WOS:000239390000001 PM 16848679 ER PT J AU Slitt, AL Cherrington, NJ Fisher, CD Negishi, M Klaassen, CD AF Slitt, AL Cherrington, NJ Fisher, CD Negishi, M Klaassen, CD TI Induction of genes for metabolism and transport by trans-stilbene oxide in livers of Sprague-Dawley and Wistar-Kyoto rats SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; MULTIDRUG-RESISTANCE PROTEIN-3; MICROSOMAL-ENZYME INDUCERS; PREGNANE-X RECEPTOR; MESSENGER-RNA; IN-VIVO; ACETAMINOPHEN METABOLITES; MEDIATED INDUCTION; RESPONSE ELEMENTS; EXPRESSION AB trans-Stilbene oxide (TSO) is a synthetic proestrogen that induces phase I and II drug-metabolizing enzymes in rat liver. The purpose of this study was to determine whether TSO also induces transporter expression in rat liver and whether gene induction in rat liver after TSO occurs in a constitutive androstane receptor ( CAR)dependent manner. Total RNA was isolated from male rat livers after treatment with TSO for up to 4 days ( 200 mg/kg, i.p., twice daily), and the mRNA levels for each gene were quantified. CYP2B1/2, CYP3A1, epoxide hydrolase, heme oxygenase-1, UGT1A6, UGT2B1, multiple drug resistance protein (Mdr) 1a and 1b, as well as multidrug resistance-associated protein (Mrp) 2, 3, and 4 mRNA were increased in livers after TSO treatment. To determine whether TSO activates gene expression in a CAR-dependent manner, male and female Wistar-Kyoto (WKY) rats were treated with TSO for 3 days. TSO induced CYP2B1/2, UGT2B1, and Mdr1b in males more than in females, suggesting that TSO could increase their expression via CAR. Conversely, TSO induced CYP3A1, epoxide hydrolase, UGT1A6, and Mrp3 similarly in both genders, indicating that induction of these genes occurs independently of CAR. TSO treatment also increased the activity of a CAR binding element luciferase reporter construct in HepG2 cells transfected with rat CAR and in mouse liver. Additionally, TSO increased antioxidant response element/electrophile response element luciferase reporter construct activity in HepG2 cells. In conclusion, in WKY rat liver, TSO increases CYP2B1/2, UGT2B1, and Mdr1b mRNA expression in a gender-dependent manner and CYP3A1, epoxide hydrolase, UGT1A6, and Mrp3 in a gender-independent manner. C1 Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. Univ Arizona, Tucson, AZ USA. Natl Inst Environm Hlth Sci, Pharmacogenet Sect, NIH, Res Triangle Pk, NC USA. RP Klaassen, CD (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM cklaasse@kumc.edu FU NIEHS NIH HHS [F32 ES011239-01, ES-09716, ES-11239, F32 ES011239, F32 ES005883, ES-07079, F32 ES011239-02] NR 33 TC 12 Z9 13 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 2006 VL 34 IS 7 BP 1190 EP 1197 DI 10.1124/dmd.105.007542 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 055GK UT WOS:000238438000016 PM 16621935 ER PT J AU Lawson, EL Clifton, JG Huang, FL Li, XS Hixson, DC Josic, D AF Lawson, Erika L. Clifton, James G. Huang, Feilei Li, Xuesong Hixson, Douglas C. Josic, Djuro TI Use of magnetic beads with immobilized monoclonal antibodies for isolation of highly pure plasma membranes SO ELECTROPHORESIS LA English DT Article DE 2-D electrophoresis; magnetic beads; monoclonal antibodies; plasma membranes; subcellular proteomics ID BLUE-NATIVE-ELECTROPHORESIS; ATP SYNTHASE COMPLEX; PROTEOMIC ANALYSIS; PROTEIN COMPLEXES; HEPATOCELLULAR CARCINOMAS; CDNA CLONING; RAT; LIVER; CELLS; EXPRESSION AB In plasma membrane proteome research, contamination of the isolated plasma membrane fraction with proteins from other organelles is still a problem. Even if highly specific isolation methods are used, such as density gradient centrifugation combined with selective extraction, contaminating proteins cannot be completely removed. To solve this problem, a protocol for the isolation of highly pure plasma membrane fractions from rat liver and two different hepatocellular carcinoma cell lines was developed. Magnetic beads with immobilized mAb's against highly expressed membrane proteins were used for specific binding of membrane vesicles and their separation from other organelles. Isolated plasma membranes were further selectively solubilized with different reagents and analyzed by use of different methods, such as Western blotting, 1- and 2-DE, and MS. Purification and further selective solubilization was validated by use of mAb's against the marker integral plasma membrane protein carcinoembryonic antigen cell adhesion molecule 1, and identification of isolated proteins by MS. The method presented here minimizes contamination with other organelles and enables further identification of membrane proteins. C1 Rhode Isl Hosp, COBRE, Ctr Canc Res Dev, CORO Ctr,Proteom Core, Providence, RI 02903 USA. Rhode Isl Hosp, Div Med Oncol, Dept Med, Providence, RI 02902 USA. Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI USA. RP Josic, D (reprint author), Rhode Isl Hosp, COBRE, Ctr Canc Res Dev, CORO Ctr,Proteom Core, Suite 4-208,1 Hoppin St, Providence, RI 02903 USA. EM Djuro_Josic@brown.edu FU NCI NIH HHS [CA 42714, F31 CA 103372]; NCRR NIH HHS [P20RR017695] NR 52 TC 64 Z9 66 U1 3 U2 12 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 JUL PY 2006 VL 27 IS 13 BP 2747 EP 2758 DI 10.1002/elps.200600059 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 068GM UT WOS:000239360800022 PM 16739230 ER PT J AU Ashok, A Hegde, RS AF Ashok, A Hegde, RS TI Prions and retroviruses: an endosomal rendezvous? SO EMBO REPORTS LA English DT Editorial Material DE prions; retrovirus budding; exosome; endosomal transport; lysosome; multivesicular body ID SCRAPIE; AGGREGATION; PROTEIN C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,Bldg 18,Room 101, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X NR 13 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUL PY 2006 VL 7 IS 7 BP 685 EP 687 DI 10.1038/sj.embor.7400749 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 058TP UT WOS:000238687800009 PM 16819462 ER PT J AU O'Connor, SM Taylor, CE Hughes, JM AF O'Connor, Siobhan M. Taylor, Christopher E. Hughes, James M. TI Emerging infectious determinants of chronic diseases SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HELICOBACTER-PYLORI INFECTION; B-VIRUS-INFECTION; HEPATITIS-B; CROHNS-DISEASE; STREPTOCOCCAL INFECTION; HUMAN-PAPILLOMAVIRUS; MULTIPLE-SCLEROSIS; VIRAL-INFECTIONS; CERVICAL-CANCER; RISK AB Evidence now confirms that noncommunicable chronic diseases can stem from infectious agents. Furthermore, at least 13 of 39 recently described infectious agents induce chronic syndromes. Identifying the relationships can affect health across populations, creating opportunities to reduce the impact of chronic disease by preventing or treating infection. As the concept is progressively accepted, advances in laboratory technology and epidemiology facilitate the detection of noncultivable, novel, and even recognized microbial origins. A spectrum of,diverse pathogens and chronic syndromes emerges, with a range of pathways from exposure to chronic illness or disability. Complex systems of changing human behavioral traits superimposed on human, microbial, and environmental factors often determine risk for exposure and chronic outcome. Yet the strength of causal evidence varies widely, and detecting a microbe does not prove causality. Nevertheless, infectious agents likely determine more cancers, immune-mediated syndromes, neurodevelopmental disorders, and other chronic conditions than currently appreciated. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIH, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. RP O'Connor, SM (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM sbo5@cdc.gov NR 51 TC 28 Z9 30 U1 0 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL PY 2006 VL 12 IS 7 BP 1051 EP 1057 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 058BO UT WOS:000238639400001 PM 16836820 ER PT J AU Andric, SA Kostic, TS Stojilkovic, SS AF Andric, SA Kostic, TS Stojilkovic, SS TI Contribution of multidrug resistance protein MRP5 in control of cyclic guanosine 5 '-monophosphate intracellular signaling in anterior pituitary cells SO ENDOCRINOLOGY LA English DT Article ID SOLUBLE GUANYLYL CYCLASE; NITRIC-OXIDE SYNTHASE; NUCLEOTIDE PHOSPHODIESTERASES; ADENOSINE 3',5'-MONOPHOSPHATE; ADENYLYL CYCLASES; AMP RELEASE; EFFLUX; CAMP; CALCIUM; PLASMA AB The energy-dependent cyclic nucleotide cellular efflux is operative in numerous eukaryotic cells and could be mediated by multidrug resistance proteins MRP4, MRP5, and MRP8. In pituitary cells, however, the operation of export pumps and their contribution to the control of intracellular cyclic nucleotide levels were not studied previously. Here we show that cellular efflux of cyclic nucleotides was detectable in normal and immortalized GH(3) pituitary cells under resting conditions and was enlarged after concurrent stimulation of cAMP and cGMP production with GHRH, corticotropin-releasing factor, vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and forskolin. In resting and stimulated cells, the efflux pumps transported the majority of de novo-produced cGMP, limiting its intracellular accumulation in a concentration range of 1-2 mu M. In contrast, only a small fraction of cAMP was released and there was a time- and concentration-dependent accumulation of this messenger in the cytosol, ranging from 1-100 mu M. Stimulation and inhibition of cGMP production alone did not affect cAMP efflux, suggesting the operation of two different transport pathways in pituitary cells. The rates of cAMP and cGMP effluxes were comparable, and both pathways were blocked by probenecid and progesterone. Pituitary cells expressed mRNA transcripts for MRP4, MRP5, and MRP8, whereas GH(3) cells expressed only transcripts for MRP5. Down-regulation of MRP5 expression in GH3 cells decreased cGMP release without affecting cAMP efflux. These results indicate that cyclic nucleotide cellular efflux plays a critical role in elimination of intracellular cGMP but not cAMP in pituitary cells and that such selectivity is achieved by expression of MRP5. C1 NICHHD, Sect Cellular Signalling, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. Univ Novi Sad, Dept Biol & Ecol, Novi Sad 21000, Serbia Monteneg. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signalling, Endocrinol & Reprod Res Branch, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov FU Intramural NIH HHS NR 58 TC 33 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2006 VL 147 IS 7 BP 3435 EP 3445 DI 10.1210/en.2006-0091 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 053NS UT WOS:000238312400032 PM 16614078 ER PT J AU Martinez, A Bengoechea, JA Cuttitta, F AF Martinez, A Bengoechea, JA Cuttitta, F TI Molecular evolution of proadrenomedullin N-terminal 20 peptide (PAMP): Evidence for gene co-option SO ENDOCRINOLOGY LA English DT Article ID O-SUCCINYLBENZOATE SYNTHASE; ENZYMATIC-ACTIVITY; OUTER-MEMBRANE; TUMOR-GROWTH; FUNCTIONAL DIVERGENCE; ADRENOMEDULLIN; MECHANISMS; SECRETION; SELECTION; RECEPTOR AB Posttranslational processing of proadrenomedullin generates two biologically active peptides, adrenomedullin ( AM) and proadrenomedullin N-terminal 20 peptide ( PAMP). Sequence comparison of homologous proadrenomedullin genes in vertebrate evolution shows a high degree of stability in the reading frame for AM, whereas PAMP sequence changes rapidly. Here we investigate the functional significance of PAMP phylogenetic variation studying two of PAMP's better characterized physiological activities, angiogenic potential and antimicrobial capability, with synthetic peptides carrying the predicted sequence for human, mouse, chicken, and fish PAMP. All tested peptides induced angiogenesis when compared with untreated controls, but chicken and fish PAMP, which lack terminal amidation, were apparently less angiogenic than their human and mouse homologs. Confirming the role of amidation in angiogenesis, Gly-extended and free acid variants of human PAMP produced responses similar to the natural nonamidated peptides. In contrast, antimicrobial activity was restricted to human PAMP, indicating that this function may have been acquired at a late time during the evolution of PAMP. Interestingly, free acid human PAMP retained antimicrobial activity whereas the Gly-extended form did not. This fact may reflect the need for maintaining a tightly defined structural conformation in the pore-forming mechanism proposed for these antimicrobial agents. The evolution of PAMP provides an example of an angiogenic peptide that developed antimicrobial capabilities without losing its original function. C1 CSIC, Inst Cajal, Dept Neuroanat & Cell Biol, Madrid 28002, Spain. Fdn Caubet Cimera, Program Infect & Immun, Bunyola 07110, Spain. NCI, Angiogenesis Core Facil, NIH, Bethesda, MD 20892 USA. RP Martinez, A (reprint author), CSIC, Inst Cajal, Dept Neuroanat & Cell Biol, Avenida Dr Arce 37, Madrid 28002, Spain. EM amartinez@cajal.csic.es RI Martinez, Alfredo/A-3077-2013; Cuttitta, Frank/B-4758-2016; OI Martinez, Alfredo/0000-0003-4882-4044; Bengoechea, Jose/0000-0002-9677-8751 NR 46 TC 14 Z9 15 U1 2 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 JUL PY 2006 VL 147 IS 7 BP 3457 EP 3461 DI 10.1210/en.2006-0150 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 053NS UT WOS:000238312400034 PM 16574790 ER PT J AU Smith, MT Lan, Q Zhang, L Vermeulen, R Shen, M Galvan, N Yin, S Rappaport, S Rothman, R AF Smith, M. T. Lan, Q. Zhang, L. Vermeulen, R. Shen, M. Galvan, N. Yin, S. Rappaport, S. Rothman, R. TI Mode of action issues in benzene cancer risk assessment and their relevance to low dose extrapolation. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. Univ N Carolina, Chapel Hill, NC 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 400 EP 400 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900005 ER PT J AU Brooks, PJ AF Brooks, P. J. TI Molecular mechanisms of neurological disease in hereditary DNA repair disorders. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIAAA, NIH, Rockville, MD 20852 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 401 EP 401 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900008 ER PT J AU Kraemer, K AF Kraemer, K. TI Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NCI, Bethesda, MD 20892 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 402 EP 402 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900009 ER PT J AU Lobanenkov, V AF Lobanenkov, V TI Outcome of twenty years of "CTCF-Research" implicates various CTCF/BORIS targets as a unifying mechanistic link in region-specific epigenetic regulation. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIAID, LIP, NIH, Rockville, MD 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 405 EP 405 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900025 ER PT J AU Bustin, M AF Bustin, M. TI Modulation of epigenetic signaling and DNA-damage responses by chromatin-binding architectural proteins. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NCI, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 411 EP 411 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900048 ER PT J AU Garcia-Diaz, M Bebenek, K Moon, AF Krahn, JM Pedersen, LC Kunkel, TA AF Garcia-Diaz, M. Bebenek, K. Moon, A. F. Krahn, J. M. Pedersen, L. C. Kunkel, T. A. TI Structure-function studies of DNA polymerases involved in NHEJ. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, Res Triangle Pk, NC 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 413 EP 413 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900057 ER PT J AU Loukinov, D Renaud, S Pugacheva, E Benhattar, J Lobanenkov, V AF Loukinov, D. Renaud, S. Pugacheva, E. Benhattar, J. Lobanenkov, V TI Identification of three BORIS promoters regulated by methylation, p53, and CTCF. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIAID, NIH, Bethesda, MD 20892 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 415 EP 415 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900063 ER PT J AU Poltoratsky, VP Prasad, R Horton, JK Wilson, SH AF Poltoratsky, V. P. Prasad, R. Horton, J. K. Wilson, S. H. TI The role of DNA polymerase beta in somatic hypermutation. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, Res Triangle Pk, NC 27709 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 415 EP 415 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900067 ER PT J AU Tessmer, I Yang, Y Sass, L Hsieh, P Erie, DA AF Tessmer, I Yang, Y. Sass, L. Hsieh, P. Erie, D. A. TI AFM and single-molecule fluorescence studies of MutS-DNA interactions reveal the mechanism of mismatch recognition. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ N Carolina, Chapel Hill, NC USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 416 EP 416 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900071 ER PT J AU McHale, CM Lan, Q Hubbard, AE Li, G Vermeulen, R Chen, J Shen, M Rappaport, SM Yin, S Smith, MT Rothman, N Zhang, L AF McHale, C. M. Lan, Q. Hubbard, A. E. Li, G. Vermeulen, R. Chen, J. Shen, M. Rappaport, S. M. Yin, S. Smith, M. T. Rothman, N. Zhang, L. TI Gene expression profiling of peripheral blood mononuclear cells from benzene-exposed workers. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. Univ N Carolina, Chapel Hill, NC 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 418 EP 418 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900076 ER PT J AU Meyer, JN Boyd, WA Haugen, AC Freedman, JH van Houten, B AF Meyer, J. N. Boyd, W. A. Haugen, A. C. Freedman, J. H. van Houten, B. TI Genotoxicity and age-related differences in nucleotide excision repair following UVC exposure in Caenorhabditis elegans. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 420 EP 420 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900086 ER PT J AU Walter, CA Grass, E Lechleiter, J Wu, J Bai, Y Park, JS Van Houten, B McMahan, CA Herbert, DC Hunter, S Reddick, R AF Walter, C. A. Grass, E. Lechleiter, J. Wu, J. Bai, Y. Park, J. S. Van Houten, B. McMahan, C. A. Herbert, D. C. Hunter, S. Reddick, R. TI EcoRI targeted to mitochondria results in mitochondrial DNA depletion and decreased mitochondrial function. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI Bai, Yidong/A-4959-2012 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 421 EP 421 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900088 ER PT J AU Shaughnessy, DT Gangarosa, L Schliebe, B DeMarini, DM Xu, Z Umbach, DM Sandler, RS Taylor, JA AF Shaughnessy, D. T. Gangarosa, L. Schliebe, B. DeMarini, D. M. Xu, Z. Umbach, D. M. Sandler, R. S. Taylor, J. A. TI Inhibition of fried meat-induced DNA damage: Use of cruciferous vegetables, yogurt, and chlorophyllin in a dietary intervention study in humans. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Sch Med, Chapel Hill, NC USA. US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 423 EP 423 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900097 ER PT J AU John, K Divi, RL Keshava, C Whipkey, DL Poirier, ML Orozco, C Shockley, M Weston, A Nath, J AF John, K. Divi, R. L. Keshava, C. Whipkey, D. L. Poirier, M. C. Orozco, C. Shockley, M. Weston, A. Nath, J. TI Modulation by chlorophyllin of benzo(a)pyrene (BP)-dependent CYP1 induction and DNA adduct formation in normal human mammary cells (NHMECs) and MCF-7 cells. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 W Virginia Univ, Morgantown, WV 26506 USA. NIOSH, CDC, Morgantown, WV USA. NCI, NIH, Bethesda, MD 20892 USA. US EPA, Washington, DC 20460 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 426 EP 426 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900104 ER PT J AU Prasad, R Liu, Y Kedar, P Deterding, L Poltorastsky, V Khodyreva, SN Lavrik, OI Wilson, SH AF Prasad, R. Liu, Y. Kedar, P. Deterding, L. Poltorastsky, V Khodyreva, S. N. Lavrik, O., I Wilson, S. H. TI Identification of HMGB1 as a new base excision repair co-factor. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI Lavrik, Olga /G-4641-2013 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 429 EP 429 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900118 ER PT J AU Theruvathu, JA Jaruga, P Dizdaroglu, M Brooks, PJ AF Theruvathu, J. A. Jaruga, P. Dizdaroglu, M. Brooks, P. J. TI The 8,5'-bond in cyclo-2'deoxyadenosine stabilizes the glycosidic bond against acid hydrolysis. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIAAA, NIH, Rockville, MD 20852 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RI Jaruga, Pawel/M-4378-2015 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 432 EP 432 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900129 ER PT J AU Witt, KL Cunningham, CK Patterson, KB Kissling, GE Dertinger, SD Livingston, E Bishop, JB AF Witt, K. L. Cunningham, C. K. Patterson, K. B. Kissling, G. E. Dertinger, S. D. Livingston, E. Bishop, J. B. TI Micronucleated erythrocyte frequencies in infants exposed to nucleoside antiretroviral drugs in utero and for 6 weeks postnatally to prevent mother-to-child transmission of HIV. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC USA. Litron Labs, Rochester, NY 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 437 EP 437 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900148 ER PT J AU Siraiuddin, P Pratt, MM Sram, RJ Manchester, DK Poirier, MC AF Siraiuddin, P. Pratt, M. M. Sram, R. J. Manchester, D. K. Poirier, M. C. TI Semi-quantitation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human placenta by immunohistochemistry (IHC) and the automated cellular imaging system (ACIS): Effect of smoking. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NCI, Carcinogen DNA Interact Sect, LCCTP, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Expt Med, Prague, Czech Republic. Univ Colorado, Sch Med, Denver, CO USA. RI Sram, Radim/H-2455-2014 OI Sram, Radim/0000-0003-4256-3816 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 440 EP 440 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900158 ER PT J AU Tucker, JD Kleinerman, R Ha, M Bhatti, P Hauptmann, M Sigurdson, A Sram, RJ Beskid, O Tawn, EJ Whitehouse, C Lindholm, C Kodama, Y Nakamura, N Vorobstova, I Oestreicher, U Stephan, G Yong, L Bauchinger, M Chung, HW Darroudi, F Roy, L Barquinero, J Livingston, G Schmid, E Blakey, D Voisin, P Littlefield, G Edwards, A AF Tucker, J. D. Kleinerman, R. Ha, M. Bhatti, P. Hauptmann, M. Sigurdson, A. Sram, R. J. Beskid, O. Tawn, E. J. Whitehouse, C. Lindholm, C. Kodama, Y. Nakamura, N. Vorobstova, I Oestreicher, U. Stephan, G. Yong, L. Bauchinger, M. Chung, H.-W. Darroudi, F. Roy, L. Barquinero, J. Livingston, G. Schmid, E. Blakey, D. Voisin, P. Littlefield, G. Edwards, A. TI International study of somatic cell translocation frequencies in control populations. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Wayne State Univ, Detroit, MI 45226 USA. NCI, NIH, DHHS, Rockville, MD USA. Acad Sci Czech Republic, Inst Expt Med, Prague, Czech Republic. Hlth Inst Cent Bohemia, Prague, Czech Republic. STUK Radiat & Nucl Safety Author, Helsinki, Finland. Radiat Effects Res Fdn, Hiroshima, Japan. Cent Res Inst Roentgenol & Radiol, St Petersburg, 30333, Russia. BfS, Obeschleissheim, Germany. NIOSH, Cincinnati, OH K1A 0L2 USA. GSF Natl Res Ctr Environm & Hlth, Neuherberg, Germany. Seoul Natl Univ, Seoul, South Korea. LUMC, Leiden, Netherlands. IRSN, Fontenay Aux Roses, France. Univ Autonoma Barcelona, Bellaterra, Spain. Ctr Dis Control & Prevent, Atlanta, GA USA. LMU Munchen, Neuherberg, Germany. Hlth Canada, Ottawa, ON, Canada. Oak Ridge Associated Univ, Oak Ridge, TN USA. Hlth Protect Agcy, Didcot, Oxon, England. RI Sram, Radim/H-2455-2014; Barquinero, Joan Francesc/L-6487-2014 OI Sram, Radim/0000-0003-4256-3816; Barquinero, Joan Francesc/0000-0003-0084-5268 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 440 EP 440 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900159 ER PT J AU Stuart, GR Copeland, WC Strand, MK AF Stuart, G. R. Copeland, W. C. Strand, M. K. TI Disruption of the Saccharomyces cerevisiae mitochondrial NADH kinase gene (POS5) results in down-regulation of the oxidative stress response and an anaerobic phenotype. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NIEHS, Res Triangle Pk, NC 27709 USA. USA, Res Off, Res Triangle Pk, NC 27709 USA. NR 1 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 444 EP 444 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900174 ER PT J AU Ming, JM Ward, Y Semino-Mora, C Robinson, EJ Cooch, C Poirier, MC Olivero, OA AF Ming, J. M. Ward, Y. Semino-Mora, C. Robinson, E. J. Cooch, C. Poirier, M. C. Olivero, O. A. TI The antiretroviral nucleoside analog zidovudine (AZT) induces centrosomal aberrations in cultured human cells in vitro. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NCI, LCCTP, Bethesda, MD 20892 USA. NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. USHUS, Bethesda, MD 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 445 EP 445 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900176 ER PT J AU Hegedus, CM Skibola, CF Warner, M Skibola, D Pfeiffer, R Clark, M Steinmaus, C Smith, AH Smith, MT Moore, LE AF Hegedus, C. M. Skibola, C. F. Warner, M. Skibola, D. Pfeiffer, R. Clark, M. Steinmaus, C. Smith, A. H. Smith, M. T. Moore, L. E. TI Association of arsenic exposure with defensin levels in the urinary proteome. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. NCI, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011; Smith, Allan/F-9249-2011 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 472 EP 472 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900281 ER PT J AU Pratt, MM Sirajuddin, P Castle, PE Phillips, DH Afework, S MacLean, AB Ragavan, N Martin, FL Olivero, OA Poirier, MC AF Pratt, M. M. Sirajuddin, P. Castle, P. E. Phillips, D. H. Afework, S. MacLean, A. B. Ragavan, N. Martin, F. L. Olivero, O. A. Poirier, M. C. TI Imaging and semiquantitation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human reproductive tissues. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NCI, LCCTP, Carcinogen DNA Interact Sect, Bethesda, MD 20892 USA. NCI, DCEG, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. Inst Canc Res, Sutton, Surrey, England. UCL, Royal Free & Univ Coll Med Sch, London, England. Univ Lancaster, Biomed Sci Unit, Lancaster, England. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2006 VL 47 IS 6 BP 475 EP 475 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900294 ER PT J AU Beyea, J Hatch, M Stellman, SD Santella, RM Teitelbaum, SL Prokopczyk, B Camann, D Gammon, MD AF Beyea, Jan Hatch, Maureen Stellman, Steven D. Santella, Regina M. Teitelbaum, Susan L. Prokopczyk, Bogdan Camann, David Gammon, Marilie D. TI Validation and calibration of a model used to reconstruct historical exposure, to polycyclic aromatic hydrocarbons for use in epidemiologic studies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast cancer; calibration; carpet dust; DNA adducts; PAH; soil; traffic; validation ID GEOGRAPHIC INFORMATION-SYSTEMS; CANCER RISK ASSESSMENT; DNA-ADDUCTS; ENVIRONMENTAL EPIDEMIOLOGY; BREAST-CANCER; LONG-ISLAND; AIR; CELLS AB OBJECTIVES: We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case-control studies of breast cancer risk Here we report the results of four exercises to validate and calibrate the model. METHODS: Model predictions of benzo[a]pyrene (BaP) concentration in sod and carpet dust were tested against measurements collected at subjects' homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH-DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. RESULTS: The data for soil, PAH-DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40-80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection. C1 Consulting Publ Interest, Lambertville, NJ 08530 USA. NCI, Div Canc & Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA. Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA. Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY 10027 USA. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. Penn State Univ, Coll Med, Hershey, PA USA. SW Res Inst, San Antonio, TX USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. RP Beyea, J (reprint author), Consulting Publ Interest, 53 Clinton St, Lambertville, NJ 08530 USA. EM jbeyea@cipi.com OI Beyea, Jan/0000-0002-0547-880X FU Intramural NIH HHS; NCI NIH HHS [CA-63021, CA-17613, CA-68384, CA-70972, CA/ES-66572, P01 CA068384, P01 CA070972, P30 CA017613, U01 CA066572]; NIEHS NIH HHS [ES-10126, P30 ES009089, P30 ES010126] NR 29 TC 17 Z9 17 U1 0 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2006 VL 114 IS 7 BP 1053 EP 1058 DI 10.1289/chp.8659 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 063QR UT WOS:000239035100036 PM 16835058 ER PT J AU Wilson, SH Schwartz, DA AF Wilson, Samuel H. Schwartz, David A. TI Disease-first: A new paradigm for environmental health science research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov; david.schwartz@niehs.nih.gov NR 0 TC 2 Z9 2 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2006 VL 114 IS 7 BP A398 EP A398 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 063QR UT WOS:000239035100002 PM 16835037 ER PT J AU Longnecker, MP AF Longnecker, MP TI Pharmacokinetic variability and the miracle of modern analytical chemistry SO EPIDEMIOLOGY LA English DT Editorial Material ID POLYCHLORINATED-BIPHENYLS; SERUM CONCENTRATIONS; CAPACITOR WORKERS; DIABETES-MELLITUS; RISK-ASSESSMENT; PCB EXPOSURE; MORTALITY; DIOXIN; MEN C1 NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnec1@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 21 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2006 VL 17 IS 4 BP 350 EP 351 DI 10.1097/01.ede.0000222510.59457.7b PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 059NX UT WOS:000238740600002 PM 16810094 ER PT J AU Ward, MH Cerhan, JR Colt, JS Hartge, P AF Ward, Mary H. Cerhan, James R. Colt, Joanne S. Hartge, Patricia TI Risk of non-Hodgkin lymphoma and nitrate and nitrite from drinking water and diet SO EPIDEMIOLOGY LA English DT Article ID N-NITROSO COMPOUNDS; ENDOGENOUS NITROSATION; URINARY-EXCRETION; ESOPHAGEAL CANCER; EXPOSURE; HEALTH; QUESTIONNAIRE; INDUCTION; SUPPLIES; LEVEL AB Introduction: Nitrate and nitrite are precursors in the in vivo formation of N-nitroso compounds, potent animal carcinogens. Methods: We conducted a population-based case-control study of non-Hodgkin lymphoma (NHL) in 1998 to 2000 in Iowa, Detroit, Seattle, and Los Angeles. Because nitrate levels were elevated in many drinking water supplies in Iowa, but not in the other study centers, we evaluated water nitrate levels and risk of NHL in Iowa only. Monitoring data for public supplies were linked to water source histories from 1960 onward. Nitrate was measured at interview homes with private wells. We limited most analyses to those with nitrate estimates for > 70% of their person-years since 1960 (181 cases, 142 controls). For those in the diet arm of the study (458 cases, 383 controls from 4 centers) and for Iowa participants in both the diet and drinking water analyses, we estimated dietary nitrate and nitrite intake using a 117-item food-frequency questionnaire that included foods high in nitrate and nitrite. Odds ratios and 95% confidence intervals were calculated using logistic regression, adjusting for the study matching factors, education, and caloric intake (diet analyses only). Results: We found no overall association with the highest quartile of average drinking water nitrate (> 2.90 mg/L nitrate-N: odds ratios = 1.2; 95% confidence interval = 0.6-2.2) or with years >= 5 mg/L (10+ years: 1.4; 0.7-2.9). We observed no evidence of an interaction between drinking water nitrate exposure and either vitamin C or red meat intake, an inhibitor and precursor, respectively, of N-nitroso compound formation. Among those in the diet arm, dietary nitrate was inversely associated with risk of NHL (highest quartile: 0.54; 0.34-0.86). Dietary nitrite intake was associated with increasing risk (highest quartile: 3.1; 1.7-5.5) largely due to intakes of bread and cereal sources of nitrite. Conclusion: Average drinking water nitrate levels below 3 mg/L were not associated with NHL risk. Our study had limited power to evaluate higher levels that deserve further study. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Iowa, Iowa City, IA USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS; NCI NIH HHS [N01-PC-67008] NR 37 TC 28 Z9 30 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2006 VL 17 IS 4 BP 375 EP 382 DI 10.1097/01.ede.0000219675.79395.9f PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 059NX UT WOS:000238740600006 PM 16699473 ER PT J AU Keim, SA Klebanoff, MA AF Keim, SA Klebanoff, MA TI Aspirin use and miscarriage risk SO EPIDEMIOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; SPONTANEOUS-ABORTION; PREGNANT-WOMEN; PREECLAMPSIA; PREVENTION; EXPOSURE; COHORT; FEVER; IQ AB Background: Recent research has found nonsteroidal antiinflammatory drugs, including aspirin, to increase the risk of miscarriage. The objective of the present study was to evaluate the association between aspirin use and miscarriage. Methods: We conducted a case-control study using data from the Collaborative Perinatal Project. This prospective cohort study recruited approximately 54,000 pregnant women at 12 sites in the United States from 1959 to 1965. Women who had miscarriages (n = 542) were matched by clinic and time in pregnancy when they came under observation to 2587 women who had live births. Participants were interviewed at each prenatal visit. Data on aspirin use were collected prospectively by in-person interviews and medical record review. Aspirin use among controls was considered only for the duration of pregnancy when the matched cases remained pregnant. The outcome of interest was miscarriage, defined as spontaneous pregnancy loss at less than 140 days from the last menstrual period. Results: Twenty-nine percent of cases and 34% of controls used aspirin during pregnancy. Aspirin use was not associated with an increased risk of miscarriage. Adjusted odds ratios ranged from 0.64 to 0.92 (95% confidence intervals = 0.48-1.38) for individual lunar months and combinations of lunar months. Conclusions: Use of aspirin during pregnancy is not associated with an increased risk of miscarriage. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Keim, SA (reprint author), 6100 Execut Blvd,Suite 5C01, Bethesda, MD 20892 USA. EM keims@mail.nih.gov RI Keim, Sarah/F-8929-2013 OI Keim, Sarah/0000-0003-3490-3649 FU Intramural NIH HHS NR 20 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2006 VL 17 IS 4 BP 435 EP 439 DI 10.1097/01.ede.0000221693.72971.b3 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 059NX UT WOS:000238740600014 PM 16755260 ER PT J AU Basso, O Wilcox, AJ AF Basso, O Wilcox, AJ TI Paternal age and delivery before 32 weeks SO EPIDEMIOLOGY LA English DT Article ID GESTATIONAL-AGE AB Background: Advanced paternal age has been linked to early preterm delivery (before 32 weeks). Methods: We analyzed live births from white, non-Hispamic primiparas recorded in U.S. birth certificates from 1995 to 2000 (excluding California). We examined 2,509,012 pregnancies of married women 20 to 34 years old, excluding unmarried women due to the high fraction of missing data on father's age. We defined the outcome according to the clinical estimate of gestation after excluding unlikely birth weights, because the estimate based on last menstrual period is particularly prone to errors at early gestations. Results: Older paternal age was not associated with increased risk of early preterm delivery. The highest estimated odds ratio among fathers 50 years or older was 1.3 (95% confidence interval 0.6-2.8) among women 20 to 24 years old. Conclusions: These U.S. data do not support an association between advanced paternal age and delivery before 32 weeks. C1 NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, MD A3-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 11 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2006 VL 17 IS 4 BP 475 EP 478 DI 10.1097/01.ede.0000219740.54796.18 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 059NX UT WOS:000238740600020 PM 16641617 ER PT J AU Peng, B Hurt, EM Hodge, DR Thomas, SB Farrar, WL AF Peng, Benjamin Hurt, Elaine M. Hodge, David R. Thomas, Suneetha B. Farrar, William L. TI DNA Hypermethylation and Partial Gene Silencing of Human Thymine-DNA Glycosylase in Multiple Myeloma Cell Lines SO EPIGENETICS LA English DT Article DE methylation; epigenetics; TDG; thymidine-DNA glycosylase; DNA repair; multiple myeloma AB Multiple myeloma (MM) has prominent features of karyotypic instability at the earliest stage, leading to extreme genetic abnormalities as the disease progresses. These successive genetic alterations can be attributed, in part, to defects in DNA repair pathways. A possible mechanism of dysregulation of the DNA repair pathway is epigenetic gene silencing. Therefore, we sought to determine the methylation status of enzymes involved in the base excision repair pathway in multiple myeloma cell lines. Here, we report the aberrant DNA methylation of TDG, one of the enzymes involved in base excision repair of damaged DNA, in several multiple myeloma cell lines but not in normal human plasma cells. DNA hypermethylation of TDG in the MM cell lines leads to lower gene expression levels that results in less efficient DNA repair activity in response to hydrogen peroxide-induced DNA damage. Expression of exogenous TDG can functionally compensate for lower repair activities of damaged DNA in the KAS-6/1 myeloma cell line, which has extensive DNA hypermethylation of the TDG promoter. Hypermethylation of DNA damage repair genes in MM cell lines may provide an explanation for the frequent genomic instability, as well as point mutations, that are encountered in MM. C1 [Hurt, Elaine M.; Hodge, David R.; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Thomas, Suneetha B.] NCI, Basic Res Program, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. [Peng, Benjamin] Univ Melbourne, Sch Dent Sci, Melbourne, Vic 3000, Australia. RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, 1050 Boyles St,Bldg 560,Rm 21-7B, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov NR 34 TC 20 Z9 23 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1559-2294 J9 EPIGENETICS JI Epigenetics PD JUL-AUG PY 2006 VL 1 IS 3 BP 138 EP 145 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V04NA UT WOS:000207063900006 PM 17965616 ER PT J AU Gerhauser, C Bartsch, H Crowell, J De Flora, S D'Incalci, M Dittrich, C Frank, N Mihich, E Steffen, C Tortora, G Gescher, A AF Gerhauser, Clarissa Bartsch, Helmut Crowell, James De Flora, Silvio D'Incalci, Maurizio Dittrich, Christian Frank, Norbert Mihich, Enrico Steffen, Christian Tortora, Giampaolo Gescher, Andreas TI Development of novel cancer chemopreventive agents in Europe - Neglected Cinderella or rising phoenix? ESF Workshop on Cancer Chemoprevention, DKFZ, Heidelberg, September 18-20, 2005 SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cancer chemoprevention; experimental animal models; chemopreventive agents; biomarkers; clinical studies; pharmaceutical industry; RAPID program; commentary; Europe; European Science Foundation (ESF) Workshop ID PROSTATE-CANCER; BREAST-CANCER; CIGARETTE-SMOKE; OLIVE OIL; CARCINOGENESIS; PREVENTION; MECHANISMS; CURCUMIN; LUNG; MICE AB Agents that prevent cancer, delay its onset, or revert premalignant conditions could have dramatic beneficial impacts on human health. Although there is an urgent need to develop cancer chemopreventive agents, researchers in the field suspect that this area of scientific endeavour in Europe leads a Cinderella existence, both in terms of perception of importance and research funding. In order to review current activities in this prevention field and to seek a consensus position, an exploratory workshop was held in September 2005 at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, sponsored mainly by the European Science Foundation (ESF), and also supported by the European Association for Cancer Research (EACR) and the German Cancer Society (DKG). The 35 experts from European countries and the United States of America assessed state-of-the-art cancer chemoprevention research in Europe. The aims that the workshop organizers had pre-defined were: i) assessment of the usefulness of animal models for agent identification; ii) review of ongoing preclinical and clinical work on novel agents; iii) discussion of potential biomarkers predictive for cancer preventive efficacy; and finally iv) the potential role that European pharmaceutical industries could play in furthering chemopreventive agent development. Overall the workshop aimed at raising awareness among European clinical and laboratory researchers of the importance of the development of novel, efficacious and safe cancer preventive agents. (c) 2006 Elsevier Ltd. All rights reserved. C1 German Canc Res Ctr, Toxicol & Canc Risk Factors, D-69120 Heidelberg, Germany. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Genoa, Dept Hlth Sci, Genoa, Italy. Ist Ric Farmacol Mario Negri, Dept Oncol, Milan, Italy. Kaiser Franz Josef Spital, Appl Canc Res Instit Translat Res Vienna, Vienna, Austria. Kaiser Franz Josef Spital, LBI ACR VIEnna, Vienna, Austria. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Bundesinst Arzneimittel & Medizinprod, Bonn, Germany. Univ Naples Federico II, Naples, Italy. Univ Leicester, Dept Canc Studies, Leicester LE1 7RH, Leics, England. RP Gerhauser, C (reprint author), German Canc Res Ctr, Toxicol & Canc Risk Factors, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM c.gerhauser@dkfz.de; ag15@leicester.ac.uk NR 43 TC 2 Z9 2 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 JUL PY 2006 VL 42 IS 10 BP 1338 EP 1343 DI 10.1016/j.ejca.2006.02.007 PG 6 WC Oncology SC Oncology GA 062UG UT WOS:000238969600015 PM 16730975 ER PT J AU Aben, KKH Baglietto, L Baffoe-Bonnie, A Coebergh, JWW Bailey-Wilson, JE Trink, B Verbeek, ALM Schoenberg, MP Witjes, JA Kiemeney, LA AF Aben, Katja K. H. Baglietto, Laura Baffoe-Bonnie, Agnes Coebergh, Jan-Willem W. Bailey-Wilson, Joan E. Trink, Barry Verbeek, Andre L. M. Schoenberg, Mark P. Witjes, J. Alfred Kiemeney, Lambertus A. TI Segregation analysis of urothelial cell carcinoma SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE urothelial cell carcinoma; segregation analysis; familial aggregation ID NON-OCULAR CANCER; BLADDER-CANCER; RETINOBLASTOMA; RELATIVES; POLYMORPHISMS; POPULATION; MODELS; RISKS AB A family history of urothelial cell carcinoma (UCC) confers an almost two-fold increased risk of developing UCC. It is unknown whether (part of) this aggregation of UCC has a Mendelian background. We performed complex segregation analyses on 1193 families ascertained through a proband with UCC of the bladder, ureter, renal pelvis or urethra, who were newly diagnosed between January 1, 1995 and December 31, 1997 and registered by two population-based cancer registries in the southeastern part of the Netherlands. Data were reported on 10 738 first-degree relatives by postal questionnaire; 101 of these relatives had UCC. All reported occurrences of UCC were verified (if possible) using medical records. Analyses were performed with the S.A.G.E. segregation package. Five restricted models (Mendelian dominant, Mendelian recessive, Mendelian co-dominant, 'no major gene' model and environmental model) were tested against the general unrestricted model. Sex and smoking status were incorporated as covariates. Strong evidence of Mendelian inheritance of UCC through a single major gene was not found in these 1193 families. However, since none of the Mendelian models could be rejected, an inherited subtype of UCC cannot be excluded. A major gene may segregate in some families but this effect may have been masked in a background of high sporadic incidence. The 'no major gene' (or sporadic) model appeared to be the most parsimonious one to describe the occurrence of UCC in these families. (c) 2006 Elsevier Ltd. All rights reserved. C1 Radboud Univ, Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands. Ctr Comprehens Canc, IKO, Nijmegen, Netherlands. Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NHGRI, State Genet Sect, NIH, Baltimore, MD USA. IKZ, Comprehens Canc Ctr, Eindhoven, Netherlands. Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Canc Res, Baltimore, MD USA. Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Radboud Univ Nijmegen Med Ctr, Dept Urol, Nijmegen, Netherlands. RP Kiemeney, LA (reprint author), Radboud Univ, Nijmegen Med Ctr, Dept Epidemiol & Biostat, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM B.Kiemeney@epib.umcn.nl RI Verbeek, A.L.M./H-8103-2014; Aben, Katja/G-9686-2016; Witjes, Fred/N-9665-2013; Kiemeney, Lambertus/D-3357-2009 OI Aben, Katja/0000-0002-0214-2147; Bailey-Wilson, Joan/0000-0002-9153-2920; Kiemeney, Lambertus/0000-0002-2368-1326 FU NCI NIH HHS [CA-06927]; NCRR NIH HHS [1 P41 RR03655] NR 27 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2006 VL 42 IS 10 BP 1428 EP 1433 DI 10.1016/j.ejca.2005.07.039 PG 6 WC Oncology SC Oncology GA 062UG UT WOS:000238969600028 PM 16737809 ER PT J AU Kogevinas, M Fernandez, F Garcia-Closas, M Tardon, A Garcia-Closas, R Serra, C Carrato, A Castano-Vinyals, G Yeager, M Chanock, SJ Lloreta, J Rothman, N Real, FX Dosemeci, M Malats, N Silverman, D AF Kogevinas, Manolis Fernandez, Francisco Garcia-Closas, Montserrat Tardon, Adonina Garcia-Closas, Reina Serra, Consol Carrato, Alfredo Castano-Vinyals, Gemma Yeager, Meredith Chanock, Stephen J. Lloreta, Josep Rothman, Nathaniel Real, Francisco X. Dosemeci, Mustafa Malats, Nuria Silverman, Debra TI Hair dye use is not associated with risk for bladder cancer: Evidence from a case-control study in Spain SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE bladder cancer; hair dyes; aromatic amines; SNPs; case-control study ID URINARY-BLADDER; PERSONAL USE; OCCUPATION; NAT2; CARCINOGENESIS; METAANALYSIS; SMOKING AB An increased bladder cancer risk has been suggested among users of hair dyes. We evaluated this association among females in a hospital-based case-control study in Spain (152 female incident cases, 166 female controls). The effect of hair dye use was also evaluated among potentially susceptible subgroups defined by NAT1, NAT2, CYP1A2, GSTM1, GSTT1 and GSTP1 genotypes. Use of any hair dye (OR = 0.8, CI 0.5-1.4) or of permanent hair dyes (OR = 0.8, CI 0.5-1.5) was not associated with increased risk. Small non-significant increases in risks were observed in a lagged analysis that ignores exposures within ten years of diagnosis (OR = 1.3, CI 0.8-2.2). No trend in risk with increasing exposure was seen for duration of use, average use or cumulative use. None of the polymorphisms examined significantly modified the hair dye associated risk. overall, this study does not support an association between hair dye use and bladder cancer. (c) 2006 Elsevier Ltd. All rights reserved. C1 CREAL, Inst Municipal Med Res, Resp & Environm Hlth Res Unit, Barcelona 08003, Spain. Med Sch Crete, Iraklion, Greece. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Oviedo, Oviedo, Spain. Hosp Univ Canarias, Tenerife, Spain. Consorci Hosp Parc Tauli, Sabadell, Spain. Univ Elche, Gen Hosp, Elche, Spain. NCI, Core Genotype Facil Adv Technol Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Hosp Mar, Dept Pathol, Barcelona, Spain. Pompeu Fabra Univ, Barcelona, Spain. RP Kogevinas, M (reprint author), CREAL, Inst Municipal Med Res, Resp & Environm Hlth Res Unit, Dr Aiguader 80, Barcelona 08003, Spain. EM kogevinas@imim.es RI Serra, C/E-6879-2014; Lloreta, J/I-2112-2014; Garcia-Closas, Montserrat /F-3871-2015; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015; OI Serra, C/0000-0001-8337-8356; Lloreta, J/0000-0003-1644-9470; Garcia-Closas, Montserrat /0000-0003-1033-2650; Real, Francisco X/0000-0001-9501-498X; Castano-Vinyals, Gemma/0000-0003-4468-1816; Malats, Nuria/0000-0003-2538-3784 FU Intramural NIH HHS NR 28 TC 39 Z9 39 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2006 VL 42 IS 10 BP 1448 EP 1454 DI 10.1016/j.ejca.2006.02.009 PG 7 WC Oncology SC Oncology GA 062UG UT WOS:000238969600031 PM 16740387 ER PT J AU Finck, A Van der Meer, JWM Schaffer, AA Pfannstiel, J Fieschi, C Plebani, A Webster, ADB Hammarstrom, L Grimbacher, B AF Finck, Anemone Van der Meer, Jos W. M. Schaffer, Alejandro A. Pfannstiel, Jessica Fieschi, Claire Plebani, Alessandro Webster, A. David B. Hammarstrom, Lennart Grimbacher, Bodo TI Linkage of autosomal-dominant common variable immunodeficiency to chromosome 4q SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE common variable immunodeficiency; recurrent infections; IgA deficiency; linkage analysis; primary immunodeficiency disorder; chromosome 4 ID SELECTIVE IGA DEFICIENCY; MAJOR HISTOCOMPATIBILITY COMPLEX; LINKED LYMPHOPROLIFERATIVE DISEASE; CLASS-III GENES; SUSCEPTIBILITY LOCUS; FAMILY; HAPLOTYPES; HYPOGAMMAGLOBULINEMIA; AGAMMAGLOBULINEMIA; PHOSPHORYLATION AB The phenotype of common variable immunodeficiency (CVID) is characterized by recurrent infections owing to hypogammaglobulinemia, with deficiency in immunoglobulin (Ig) G and at least one of IgA or IgM. Family studies have shown a genetic association between CVID and selective IgA deficiency (IgAD), the latter being a milder disorder compatible with normal health. Approximately 20-25% of CVID cases are familial, if one includes families with at least one case of CVID and one of IgAD. Nijenhuis et al described a five-generation family with six cases of CVID, five cases of IgAD, and three cases of dysgammaglobulinemia. We conducted a genome-wide scan on this family seeking genetic linkage. One interval on chromosome 4q gives a peak multipoint LOD score of 2.70 using a strict model that treats only the CVID patients and one obligate carrier with dysgammaglobulinemia as affected. Extending the definition of likely affected to include IgAD boosts the peak multipoint LOD score to 3.38. The linkage interval spans at least from D4S2361 to D4S1572. We extended our study to a collection of 32 families with at least one CVID case and a second case of either CVID or IgAD. We used the same dominant penetrance model and genotyped and analyzed nine markers on 4q. The 32 families have a peak multipoint LOD score under heterogeneity of 0.96 between markers D4S423 and D4S1572 within the suggested linkage interval of the first family, and an estimated proportion of linked families (a) of 0.32, supporting the existence of a disease-causing gene for autosomal-dominant CVID/IgAD on chromosome 4q. C1 Univ Hosp Freiburg, Div Rheumatol & Clin Immunol, Dept Med, D-79106 Freiburg, Germany. Dept Med, Nijmegen, Netherlands. Univ Nijmegen, Ctr Infect Dis, Nijmegen, Netherlands. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Hop St Louis, Ctr Hayem, Paris, France. Univ Brescia, Dept Pediat, Brescia, Italy. Univ Brescia, Inst Med Angelo Novicelli, Brescia, Italy. Royal Free Hosp, Dept Clin Immunol, London NW3 2QG, England. Karolinska Inst Huddinge, Div Clin Immunol, Dept Med, Stockholm, Sweden. RP Grimbacher, B (reprint author), Univ Hosp Freiburg, Div Rheumatol & Clin Immunol, Dept Med, Hugstetterstr 55, D-79106 Freiburg, Germany. EM grimbacher@medizin.ukl.uni-freiburg.de RI Plebani, Alessandro/C-8593-2011; Schaffer, Alejandro/F-2902-2012; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 FU Intramural NIH HHS NR 52 TC 24 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JUL PY 2006 VL 14 IS 7 BP 867 EP 875 DI 10.1038/sj.ejhg.5201634 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 061RM UT WOS:000238890100013 PM 16639407 ER PT J AU Wooldridge, L Scriba, TJ Milicic, A Laugel, B Gostick, E Price, DA Phillips, RE Sewell, AK AF Wooldridge, Linda Scriba, Thomas J. Milicic, Anita Laugel, Bruno Gostick, Emma Price, David A. Phillips, Rodney E. Sewell, Andrew K. TI Anti-coreceptor antibodies profoundly affect staining with peptide-MHC class I and class II tetramers SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4; CD8; peptide-MHC tetrarners; T cell activation; T cell receptors ID T-CELL-RECEPTOR; HUMAN CD8 CORECEPTOR; BINDING-SITE; FUNCTIONAL REQUIREMENT; CLONAL HETEROGENEITY; CRYSTAL-STRUCTURE; MULTIMER BINDING; ALPHA-3 DOMAIN; ACTIVATION; MOLECULES AB The T cell coreceptors CD8 and CD4 bind to invariable regions of peptide-MHC class I (pMHCI) and class II (pMHCII) molecules, respectively, and facilitate antigen recognition by a number of mechanisms. It is established that some antibodies (Ab) specific for the CD8 molecule, which stabilizes TCR/pMHCI interactions, can alter the binding of pMHCI tetramers to cell surface TCR. In contrast, the extremely weak pMHCII/CD4 interaction does not stabilize TCR/pMHCII interactions or contribute to cognate tetramer binding; consequently, it is assumed that anti-CD4 Ab do not affect pMHCII binding. Here, we used a panel of point-mutated HLA A2 molecules with a range of affinities for CD8 spanning over three orders of magnitude to demonstrate that anti-CD8 Ab-mediated inhibition of pMHCI tetramer binding and cognate T cell activation correlates directly with the strength of the pMHCI/CD8 interaction. Further, some anti-CD4 Ab were found to block pMHCII tetramer binding; these effects were also paralleled in T cell activation assays. In sum, these data challenge the assertion that anticoreceptor Ab exert their effects on T cell activation and pMHC binding solely by blocking pMHC/coreceptor interactions. C1 T Cell Modulat Grp, Oxford OX1 3SY, England. Persistent Viruses Res Grp, Oxford, England. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sewell, AK (reprint author), T Cell Modulat Grp, Peter Medawar Bldg Pathogen Res,S Pk Rd, Oxford OX1 3SY, England. EM andy.sewell@ndm.ox.ac.uk RI Milicic, Anita/B-7693-2011; Scriba, Thomas/H-3633-2013; Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Sewell, Andrew/0000-0003-3194-3135 FU Medical Research Council [G108/441] NR 39 TC 12 Z9 12 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2006 VL 36 IS 7 BP 1847 EP 1855 DI 10.1002/eji.200635886 PG 9 WC Immunology SC Immunology GA 067HI UT WOS:000239292100022 PM 16783852 ER PT J AU Dina, OA Messing, RO Levine, JD AF Dina, Olayinka A. Messing, Robert O. Levine, Jon D. TI Ethanol withdrawal induces hyperalgesia mediated by PKC epsilon SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ethanol; hyperalgesia; PKC epsilon; withdrawal ID PROTEIN-KINASE-C; PAINFUL PERIPHERAL NEUROPATHY; STREPTOZOTOCIN-DIABETIC RAT; ALCOHOL-WITHDRAWAL; INFLAMMATORY PAIN; SEXUAL-DIMORPHISM; REPEATED EPISODES; LIQUID DIET; CELL-DEATH; MICE AB Symptoms of ethanol withdrawal include heightened responses to sensory stimuli, as well as tremors and convulsions. We tested the hypothesis that repeated episodes of ethanol intake and withdrawal exacerbate the symptoms of alcohol-induced peripheral neuropathy. In contrast to the hyperalgesia produced when an alcohol (6.5%)-containing diet was fed continuously to male rats which took 4 weeks to develop (Dina et al., 2000), feeding alcohol ( 6.5%) in repeated cycles of 4 days of alcohol followed by 3 days without alcohol resulted in a withdrawal-induced hyperalgesia that began at the end of one weekly cycle and reached a maximum during the fourth cycle. For ethanol withdrawal to produce hyperalgesia, ethanol consumption needed to be terminated for a period of 2 days. Paradoxically, as the amount of alcohol consumed decreased, the hyperalgesia induced by withdrawal developed more rapidly, being maximal between 1.4 and 1.6% ethanol. These results suggest that continued exposure to ethanol also has a neuroprotective effect. Withdrawal-induced hyperalgesia, similar to the hyperalgesia induced by continuous, chronic alcohol intake, was inhibited reversibly by intrathecal administration of an antisense oligodeoxynucleotide to protein kinase C (PKC)epsilon. C1 Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Ernest Gallo Clin & Res Ctr, Emeryville, CA USA. Univ Calif San Francisco, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. EM Jon.Levine@ucsf.edu RI Messing, Robert/D-3642-2015 OI Messing, Robert/0000-0002-5345-4431 FU NIAAA NIH HHS [AA013875] NR 66 TC 31 Z9 31 U1 3 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2006 VL 24 IS 1 BP 197 EP 204 DI 10.1111/j.1460-9568.2006.04886.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 063FU UT WOS:000239004100021 PM 16800864 ER PT J AU Ravel, S Richmond, BJ AF Ravel, Sabrina Richmond, Barry J. TI Dopamine neuronal responses in monkeys performing visually cued reward schedules SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE basal ganglia; motivation; prediction; salience; substantia nigra ID MIDBRAIN DOPAMINE; SUBSTANTIA-NIGRA; RHINAL CORTEX; STIMULI; SIGNALS; PREDICTION; INHIBITION; MOTIVATION; SACCADES; NUCLEUS AB Dopamine neurons are important for reward-related behaviours. They have been recorded during classical conditioning and operant tasks with stochastic reward delivery. However, daily behaviour, although frequently complex in the number of steps, is often very predictable. We studied the responses of 75 dopamine neurons during schedules of trials in which the events and related reward contingencies could be well-predicted, within and across trials. In this visually cued reward schedule task, a visual cue tells the monkeys exactly how many trials, 1, 2, 3, or 4, must be performed to obtain a reward. The number of errors became larger as the number of trials remaining before the reward increased. Dopamine neurons frequently responded to the cues at the beginning and end of the schedules. Approximately 75% of the first-cue responsive neurons did not distinguish among the schedules that were beginning even though the cues were different. Approximately half of the last-cue responsive neurons depended on which schedule was ending, even though the cue signalling the last trial was the same in all schedules. Thus, the responses were related to what the monkey knew about the relation between the cues and the schedules, not the identity of the cues. These neurons also frequently responded to the go signal and/or to the OK signal indicating the end of a correctly performed trial whether a reward was forthcoming or not, and to the reward itself. Thus, dopamine neurons seem to respond to behaviourally important, i.e. salient, events even when the events have been well-predicted. C1 NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov NR 37 TC 26 Z9 26 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2006 VL 24 IS 1 BP 277 EP 290 DI 10.1111/j.1460-9568.2006.04905.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 063FU UT WOS:000239004100029 PM 16882024 ER PT J AU Hucho, TB Dina, OA Kuhn, J Levine, JD AF Hucho, Tim B. Dina, Olayinka A. Kuhn, Julia Levine, Jon D. TI Estrogen controls PKC epsilon-dependent mechanical hyperalgesia through direct action on nociceptive neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cyclic AMP; Epac; intracellular signaling; nociception; rat ID PROTEIN-KINASE-C; PAINFUL PERIPHERAL NEUROPATHY; ROOT GANGLION NEURONS; FEMALE RATS; INFLAMMATORY PAIN; SEXUAL-DIMORPHISM; RECEPTOR-ALPHA; INTRACELLULAR CALCIUM; SPINAL-CORD; IN-VITRO AB Protein kinase C epsilon (PKC epsilon) is an important intracellular signaling molecule in primary afferent nociceptors, implicated in acute and chronic inflammatory as well as neuropathic pain. In behavioral experiments inflammatory mediators produce PKC epsilon-dependent hyperalgesia only in male rats. The mechanism underlying this sexual dimorphism is unknown. We show that the hormone environment of female rats changes the nociceptive signaling in the peripheral sensory neuron. This change is maintained in culture also in the absence of a gender-simulating environment. Stimulation of beta(2)-adrenergic receptors (beta(2)-AR) leads to PKC epsilon activation in cultured dorsal root ganglia (DRG) neurons derived from male but not from female rats. Addition of estrogen to male DRG neurons produces a switch to the female phenotype, namely abrogation of beta(2)-AR-initiated activation of PKC epsilon. Estrogen interferes downstream of the beta(2)-AR with the signaling pathway leading from exchange protein activated by cAMP (Epac) to PKC epsilon. The interfering action is fast indicating a transcriptional-independent mechanism. Estrogen has a dual effect on PKC epsilon. If applied before beta(2)-AR or Epac stimulation, estrogen abrogates the activation of PKC epsilon. In contrast, estrogen applied alone leads to a brief translocation of PKC epsilon. Also in vivo the activity of estrogen depends on the stimulation context. In male rats, intradermal injection of an Epac activator or estrogen alone induces mechanical hyperalgesia through a PKC epsilon-dependent mechanism. In contrast, injection of estrogen preceding the activation of Epac completely abrogates the Epac-induced mechanical hyperalgesia. Our results suggest that gender differences in nociception do not reflect the use of generally different mechanisms. Instead, a common set of signaling pathways can be modulated by hormones. C1 Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. RP Hucho, TB (reprint author), Max Planck Inst Mol Genet, Dept Mol Human Genet, Ihnestr 73, D-14195 Berlin, Germany. EM hucho@molgen.mpg.de RI Hucho, Tim/F-8973-2010 FU NIAMS NIH HHS [AR052106] NR 52 TC 55 Z9 59 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2006 VL 24 IS 2 BP 527 EP 534 DI 10.1111/j.1460-9568.2006.04913.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 065IH UT WOS:000239152900020 PM 16836642 ER PT J AU Ward, JM AF Ward, Jerrold M. TI Lymphomas and leukemias in mice SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT 3rd European Congress of Toxicologic Pathology CY SEP 29-OCT 01, 2005 CL Univ Copenhagen, Royal Vet & Agr, Copenhagen, DENMARK SP European Soc Toxicol Pathol HO Univ Copenhagen, Royal Vet & Agr DE lymphoma; leukaemia; mice; spleen; carcinogenesis; lymphocytes; immunohistochemistry ID HEMATOPOIETIC NEOPLASMS; BETHESDA PROPOSALS; SPONTANEOUS TUMORS; CD-1 MICE; RATS; CLASSIFICATION; CARCINOGENICITY AB Lymphomas are among the most common tumors in many strains and stocks of mice, especially those used in safety assessment. CD-1, C57BL/6, B6C3F1 and B6;129 mice develop 10-50% incidences of lymphomas in aging mice. Most of the tumors are B-cell lymphomas of the follicular type, arising in spleen, mesenteric lymph node and/or Peyer's patches. Lymphomas and leukemias may be induced by chemicals, retroviruses and irradiation. Genetics also play a major role in mouse lymphomagenesis and leukemogenesis. The most potent chemical carcinogens require only a single injection in young mice to induce a high incidence of lymphomas, often thymic T-cell lymphoblastic lymphomas. Several genetically engineered mouse lines have high incidences of these tumors. In 2-year carcinogenesis bioassays, increases of incidences of B-cell lymphomas (which occur naturally in controls) are indicative of less potent carcinogens. Classifications of the lymphomas and leukemias have evolved over the years. The practical WHO toxicologic pathology lymphoma and leukemia classification was developed by collaboration between the US STP, RITA, BSTP and JSTP. A more recent mouse lymphoma and leukemia classification was published by a committee of the US NCI Mouse Models of Human Cancers Consortium. This classification follows closely the more detailed human WHO classification and can be used for mouse models of lymphoma and leukemia. (c) 2006 Elsevier GmbH. All rights reserved. C1 NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Ward, JM (reprint author), NIAID, Comparat Med Branch, NIH, Twinbrook 3,MSC-8135, Bethesda, MD 20892 USA. EM jw116y@nih.gov NR 26 TC 24 Z9 24 U1 0 U2 4 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD JUL PY 2006 VL 57 IS 5-6 BP 377 EP 381 DI 10.1016/j.etp.2006.01.007 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 063RL UT WOS:000239037200010 PM 16713211 ER PT J AU Yoshimoto, T Boehm, M Olive, M Crook, MF San, H Langenickel, T Nabel, EG AF Yoshimoto, T Boehm, M Olive, M Crook, MF San, H Langenickel, T Nabel, EG TI The arginine methyltransferase PRMT2 binds RB and regulates E2F function SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE protein arginine methyltransferases; PRMT2; retinoblastoma gene product; RB; AdoMet binding domain; E2F; cell cycle ID S-PHASE ENTRY; CELL-CYCLE; PROTEIN METHYLTRANSFERASE; DEREGULATED EXPRESSION; N-METHYLTRANSFERASE; GENE-EXPRESSION; HISTONE H3; TRANSCRIPTION; METHYLATION; IDENTIFICATION AB The retinoblastoma gene product (RB) is an important regulator of E2F activity. RB recruits a number of proteins, including HDACs, SWI/SNF complex, lysine methyl transferase (SUV39H1) and DNA methyltransferase (DNMT1), all of which negatively regulate E2F activity with RB. Here, we show that RB interacts with PRMT2, a member of the protein arginine methyltransferase family, to regulate E2F activity. PRMT2 directly bound and interacted with RB through its AdoMet binding domain, in contrast to other PRMT proteins, including PRMT1, PRMT3 and PRMT4. In reporter assays, PRMT2 repressed E2F1 transcriptional activity in an RB-dependent manner. PRMT2 formed a ternary complex with E2F1 in the presence of RB. To further explore the role of endogenous PRMT2 in the regulation of E2F activity, the PRMT2 gene was ablated in mice by gene targeting. Compared with PRMT2(+/+) mouse embryonic fibroblasts (MEFs), PRMT2(-/-) MEFs demonstrated increased E2F activity and early S phase entry following release of serum starvation. Vascular injury to PRMT2(-/-) arteries results in a hyperplastic response, consistent with increased G1-S phase progression. Taken together, these findings demonstrate a novel mechanism for the regulation of E2F activity by a member of the protein arginine methyltransferase family. Published by Elsevier Inc. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Cardiovasc Branch, NIH, 31 Ctr Dr,31-5A48, Bethesda, MD 20892 USA. EM nabele@nih.gov FU Intramural NIH HHS NR 42 TC 40 Z9 46 U1 3 U2 6 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2006 VL 312 IS 11 BP 2040 EP 2053 DI 10.1016/j.yexcr.2006.03.001 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 057NG UT WOS:000238601900012 PM 16616919 ER PT J AU Kim, AL Zhu, YC Zhu, HJ Han, L Kopelovich, L Bickers, DR Athar, M AF Kim, AL Zhu, YC Zhu, HJ Han, L Kopelovich, L Bickers, DR Athar, M TI Resveratrol inhibits proliferation of human epidermoid carcinoma A431 cells by modulating MEK1 and AP-1 signalling pathways SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE activating protein-1; cell cycle; extracellular signal-regulated protein kinase; resveratrol ID C-JUN; CYCLE PROGRESSION; RETINOBLASTOMA PROTEIN; D1 COMPLEX; FOS; PHOSPHORYLATION; ARREST; CANCER; ACTIVATION; KINASE AB Resveratrol (trans-3,4', 5-trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin found in grapes, and has been shown to inhibit the growth of various types of cancer cells. We investigated the mechanism of the antiproliferative effect of resveratrol in A431-transformed keratinocytes harbouring mutant p53, and show that it is accompanied by G1 cell cycle arrest, which coincides with a marked inhibition of G1 cell cycle regulatory proteins, including cyclins A and D1 and cyclin-dependent kinase (CDK)6 and p53-independent induction of p21WAF1. Cell cycle arrest was also associated with the accumulation of hypophosphorylated Rb and p27KIP1. Resveratrol inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)l > extracellular signal-regulated protein kinase (ERK)1/2 signalling, downregulated c-Jun, and suppressed activating protein (AP)-1 DNA-binding and promoter activity. In addition, the inhibition of MEK1 > ERK1/2 signalling appears to be independent of retinoblastoma protein (pRb) hypophosphorylation in A431 cells, as PD098059 did not suppress pRb phosphorylation. Our results demonstrate that resveratrol affects multiple cellular targets in A431 cells, and that the downregulation of both AP-1 and pRb contributes to its antiproliferative activity in these cells. C1 Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Kim, AL (reprint author), Columbia Univ Coll Phys & Surg, Dept Dermatol, 630 W 168th St VC15-204, New York, NY 10032 USA. EM ak309@columbia.edu FU NCI NIH HHS [R01 CA-097249-01]; NIAMS NIH HHS [K01-AR048582-03] NR 39 TC 63 Z9 70 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JUL PY 2006 VL 15 IS 7 BP 538 EP 546 DI 10.1111/j.1600-0625.2006.00445.x PG 9 WC Dermatology SC Dermatology GA 056RD UT WOS:000238541900008 PM 16761963 ER PT J AU House, SB Rusnak, M Liu, XH Youle, RJ Gainer, H AF House, Shirley B. Rusnak, Milan Liu, Xiu-Huai Youle, Richard J. Gainer, Harold TI Bcl-xL and caspase inhibition increase the survival of rat oxytocin and vasopressin magnocellular neurons in organotypic culture SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hypothalamus; apoptosis; Bcl-2; CNTF; programmed cell death ID CILIARY NEUROTROPHIC FACTOR; HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; CENTRAL-NERVOUS-SYSTEM; CELL-DEATH; SUPRAOPTIC NUCLEUS; APOPTOSIS; REGENERATION; NEUROPHYSIN; BCL-X(L); PROTEIN AB Hypothalamic magnocellular neurons (MCNs) are highly vulnerable to axotomy-induced cell death in vivo and in vitro. In this study, we determined whether the anti-apoptotic agent Bcl-xL, a member of the Bcl-2 family which prevents programmed cell death in the central nervous system, can rescue oxytocin (OT) and vasopressin (VP) MCNs in the supraoptic nucleus (SON) in organotypic culture. We found that the novel, membrane permeant form of Bcl-xL that we employed in these studies protected both OT and VP MCNs from degeneration as long as the Bel-xL was present in the medium. In contrast, z-VAD-fink, an inhibitor of caspases that are involved in apoptosis, was less effective in that it significantly rescued OT MCNs (P < 0.01) but not VP MCNs (P > 0.09). Unlike the Bcl-xL, Z-VAD-fmk's effectiveness in reducing MCN cell death was not sustained for the full 15 days in vitro. Published by Elsevier Inc. C1 NINDS, Neurochem Lab, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, Surg Neurol Branch, NIH, Bldg 49,Room 5A78, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov FU Intramural NIH HHS NR 30 TC 6 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2006 VL 200 IS 1 BP 267 EP 271 DI 10.1016/j.expneurol.2006.02.009 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 070EL UT WOS:000239503000030 PM 16624298 ER PT J AU Arbab, AS Liu, W Frank, JA AF Arbab, Ali S. Liu, Wei Frank, Joseph A. TI Cellular magnetic resonance imaging: current status and future prospects SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE cell tracking; cellular MRI; gene delivery; SPIO; stem cells ID SUPERPARAMAGNETIC IRON-OXIDE; MESENCHYMAL STEM-CELLS; POSITRON-EMISSION-TOMOGRAPHY; TRANSFERRIN RECEPTOR GENE; MANGANESE-ENHANCED MRI; IN-VIVO TRACKING; CONTRAST AGENTS; TRANSFECTION AGENTS; INTRACELLULAR-LOCALIZATION; FIELD INHOMOGENEITIES AB Cellular magnetic resonance imaging (CMRI) allows for the tracking of the temporal and spatial migration of cells labeled with MR contrast agents within organs and tissues. This rapidly growing area of experimental research has the potential of translating from bench to bedside and may be used in conjunction with cellular therapy clinical trials or in the evaluation of novel drug therapies. Ex vivo labeling of nonphagocytic cells with superparamagnetic iron oxide nanoparticles or paramagnetic contrast agents (i.e., gadolinium or manganese) allows for the detection of single cells or clusters of labeled cells within target tissues using CMRI following either direct implantation or intravenous injection. However, prior to the translation of experimental cell labeling studies to clinical trials, it is essential to perform preclinical evaluation to demonstrate a lack of toxicity, the ability to scale-up labeling using good manufacturing practice and the ability to detect cells by in vivo MRI in relevant model systems. C1 Henry Ford Hlth Syst, Detroit, MI 48202 USA. Philips Res N Amer, Briarcliff Manor, NY 10510 USA. NIH, Lab Diagnost Radiol Res, Expt Neuroimaging Sect, Bethesda, MD 20892 USA. RP Arbab, AS (reprint author), Henry Ford Hlth Syst, 1 Ford Pl,2F, Detroit, MI 48202 USA. EM saali@rad.hfh.edu NR 112 TC 99 Z9 111 U1 1 U2 28 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD JUL PY 2006 VL 3 IS 4 BP 427 EP 439 DI 10.1586/17434440.3.4.427 PG 13 WC Engineering, Biomedical SC Engineering GA 106LL UT WOS:000242101900009 PM 16866640 ER PT J AU Yamaguchi, Y Takahashi, K Zmudzka, BZ Kornhauser, A Miller, SA Tadokoro, T Berens, W Beer, JZ Hearing, VJ AF Yamaguchi, Yuji Takahashi, Kaoruko Zmudzka, Barbara Z. Kornhauser, Andrija Miller, Sharon A. Tadokoro, Taketsugu Berens, Werner Beer, Janusz Z. Hearing, Vincent J. TI Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis SO FASEB JOURNAL LA English DT Article DE pigmentation; melanocyte; melanosome; photoprotection ID REGULATES P53-DEPENDENT APOPTOSIS; SUNBURN CELL-FORMATION; ULTRAVIOLET-RADIATION; IN-VITRO; P53; MELANIN; CANCER; PHOTOPRODUCTS; EXPRESSION; MUTATIONS AB Melanin plays an important role in protecting the skin against UV radiation, and melanomas and basal/squamous cell carcinomas occur more frequently in individuals with fair/light skin. We previously reported that levels of melanin correlate inversely with amounts of DNA damage induced by UV in normal human skin of different racial/ethnic groups. We have now separately examined DNA damage in the upper and lower epidermal layers in various types of skin before and after exposure to UV and have measured subsequent apoptosis and phosphorylation of p53. The results show that two major mechanisms underlie the increased photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin, suggesting that the pigmented epidermis is an efficient UV filter. Second, UV-induced apoptosis is significantly greater in darker skin, which suggests that UV-damaged cells may be removed more efficiently in pigmented epidermis. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 FU Intramural NIH HHS NR 42 TC 95 Z9 97 U1 3 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 JUL PY 2006 VL 20 IS 9 BP 1486 EP + DI 10.1096/fj.06-5725fje PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RP UT WOS:000240266000026 PM 16793869 ER PT J AU Simon, DM Arikan, MC Srisuma, S Bhattacharya, S Tsai, LW Ingenito, EP Gonzalez, F Shapiro, SD Mariani, TJ AF Simon, Dawn M. Arikan, Meltem C. Srisuma, Sorachai Bhattacharya, Soumyaroop Tsai, Larry W. Ingenito, Edward P. Gonzalez, Frank Shapiro, Steven D. Mariani, Thomas J. TI Epithelial cell PPAR gamma contributes to normal lung maturation SO FASEB JOURNAL LA English DT Article DE Cre recombinase; Clara cell; lung development; airspace enlargement ID ACTIVATED-RECEPTOR-GAMMA; MONOCYTE-DERIVED MACROPHAGES; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; TERMINAL DIFFERENTIATION; EXTRACELLULAR-MATRIX; ADIPOSE-TISSUE; MOUSE MODEL; INFLAMMATION; CANCER AB Peroxisome proliferator-activated receptor (PPAR)-gamma is a member of the nuclear hormone receptor superfamily that can promote cellular differentiation and organ development. PPAR gamma expression has been reported in a number of pulmonary cell types, including inflammatory, mesenchymal, and epithelial cells. We find that PPAR gamma is prominently expressed in the airway epithelium in the mouse lung. In an effort to define the physiological role of PPAR gamma within the lung, we have ablated PPAR gamma using a novel line of mice capable of specifically targeting the airway epithelium. Airway epithelial cell PPAR gamma-targeted mice display enlarged airspaces resulting from insufficient postnatal lung maturation. The increase in airspace size is accompanied by alterations in lung physiology, including increased lung volumes and decreased tissue resistance. Genome-wide expression profiling reveals a reduction in structural extracellular matrix (ECM) gene expression in conditionally targeted mice, suggesting a disruption in epithelial-mesenchymal interactions necessary for the establishment of normal lung structure. Expression profiling of airway epithelial cells isolated from conditionally targeted mice indicates PPAR gamma regulates genes encoding known PPAR gamma targets, additional lipid metabolism enzymes, and markers of cellular differentiation. These data reveal airway epithelial cell PPAR gamma is necessary for normal lung structure and function. C1 Harvard Univ, Div Pulm & Crit Care Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Resp Dis, Boston, MA 02115 USA. Mahidol Univ, Siriraj Hosp, Fac Med, Dept Physiol, Bangkok 10700, Thailand. Natl Canc Inst, Lab Metab, Bethesda, MD USA. RP Mariani, TJ (reprint author), Harvard Univ, Div Pulm & Crit Care Med, Brigham & Womens Hosp, Sch Med, 75 Francis St,Thorn 908, Boston, MA 02115 USA. EM tmariani@rics.bwh.harvard.edu RI Bhattacharya, Soumyaroop/E-7669-2010; OI Bhattacharya, Soumyaroop/0000-0003-1140-7845 FU NHLBI NIH HHS [HL071885, HL70321] NR 41 TC 61 Z9 61 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2006 VL 20 IS 9 BP 1507 EP + DI 10.1096/fj.05-5410fje PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RP UT WOS:000240266000033 PM 16720732 ER PT J AU Bloom, MS Schisterman, EF Hediger, ML AF Bloom, Michael S. Schisterman, Enrique F. Hediger, Mary L. TI Selecting controls is not selecting "normals": Design and analysis issues for studying the etiology of polycystic ovary syndrome SO FERTILITY AND STERILITY LA English DT Article DE bias; cas-control study; collider stratification; methods; odds ratio; PCOS; polycystic ovary syndrome; prevalence ID INSULIN-RESISTANCE; YOUNG-WOMEN; DIAGNOSTIC-CRITERIA; CARDIOVASCULAR RISK; GLUCOSE-TOLERANCE; ANDROGEN EXCESS; GENETIC-BASIS; SYNDROME PCOS; ASIAN WOMEN; EPILEPSY AB Introduction: Polycystic ovary syndrome (PCOS) is a highly prevalent disorder among postmenarcheal premenopausal women, accounting for much of anovulatory infertility, and it is associated with several comorbidities. The natural history of PCOS, as well as hypotheses regarding its etiology, facilitates employment of the case-control study design. However, a review of the literature suggested that inconsistency of research findings in relation to the etiology of PCOS might be, in part, due to the different choice of controls for case-control design and application. Design: Investigators have often employed "healthy" control groups and neglected to consider the tenability of the "rare disease" assumption in the analysis when instituting the case control strategy. This might result in the introduction of a positive bias or overestimation of odds ratios, producing an effect estimate that is more extreme than that in the underlying population. Using several quantitative, through hypothetical literature-driven examples, this bias is described and demonstrated. In addition, recommendations, are provided with regard to case-sampling strategy when the rare disease assumption is untenable, as it may frequently be in studies of PCOS. Conclusion(s): It is hoped that more consistent case-control methodology, in concert with recent consensus on case definition, will more effectively facilitate the elucidation of the causes and consequences of PCOS. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Schisterman, EF (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03,MSC 7510, Bethesda, MD 20892 USA. EM SchisteE@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS NR 86 TC 17 Z9 19 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 JUL PY 2006 VL 86 IS 1 BP 1 EP 12 DI 10.1016/j.fertnstert.2005.09.066 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 062YO UT WOS:000238983100001 PM 16750830 ER PT J AU Rubinow, DR Schmidt, PJ AF Rubinow, David R. Schmidt, Peter J. TI Gonadal steroid regulation of mood: The lessons of premenstrual syndrome SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE gonadal steroids; mood; depression; hormones; neurocircuitry; emotion; PMS; menstrual cycle; cognition ID ANTERIOR CINGULATE CORTEX; ACTIVATED PROTEIN-KINASE; ELEMENT-BINDING PROTEIN; PREFRONTAL CORTEX; ESTROGEN-RECEPTOR; RAT-BRAIN; OVARIAN HORMONES; MENSTRUAL-CYCLE; HUMAN-MEMORY; FEMALE RATS AB New models for menstrual cycle-related mood disorders provide unique opportunities to gain insight into the processing of emotional information and the regulation of mood state by reproductive steroids. This paper reviews the role of reproductive steroids in affect regulation and in premenstrual dysphoric disorder (PMD), parses PMD into component processes that suggest potential mediating neurocircuitry, and highlights the importance of and potential contributors to the differential sensitivity that permits reproductive steroids to destabilize mood in some but not all women. (c) 2006 Elsevier Inc. All rights reserved. C1 NIMH, Behav Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM rubinowd@mail.nih.gov FU Intramural NIH HHS NR 88 TC 59 Z9 60 U1 2 U2 17 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 JUL PY 2006 VL 27 IS 2 BP 210 EP 216 DI 10.1016/j.yfrne.2006.02.003 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 065RP UT WOS:000239177300004 PM 16650465 ER PT J AU Taubenberger, JK AF Taubenberger, Jeffery K. TI Influenza hemagglutinin attachment to target cells: 'birds do it, we do it...' SO FUTURE VIROLOGY LA English DT Editorial Material ID HUMAN AIRWAY; VIRUSES; RECEPTORS; BINDING C1 Armed Forces Inst Pathol, Dept Mol Pathol, Rockville, MD 20306 USA. NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), Armed Forces Inst Pathol, Dept Mol Pathol, Rockville, MD 20306 USA. EM taubenbe@afip.osd.mil FU Intramural NIH HHS [Z01 AI000986-01] NR 12 TC 11 Z9 11 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 J9 FUTURE VIROL JI Future Virol. PD JUL PY 2006 VL 1 IS 4 BP 415 EP 418 DI 10.2217/17460794.1.4.415 PG 4 WC Virology SC Virology GA 209ZH UT WOS:000249426000002 PM 18820731 ER PT J AU Best, SM Mitzel, DN Bloom, ME AF Best, Sonja M. Mitzel, Dana N. Bloom, Marshall E. TI Action and reaction: the arthropod-borne flaviviruses and host interferon responses SO FUTURE VIROLOGY LA English DT Review DE flavivirus; inhibition; innate immunity; interferon; interferon regulatory factor-3; Janus kinase-signal transducer and activator of transcription; mosquito; tick ID WEST-NILE-VIRUS; HEPATITIS-C VIRUS; HUMAN DENDRITIC CELLS; VIRAL-DIARRHEA-VIRUS; DENGUE VIRUS; JAPANESE ENCEPHALITIS; REGULATORY FACTOR-3; ALPHA-INTERFERON; MOLECULAR DETERMINANTS; ANTIVIRAL RESPONSE AB The arthropod-borne flaviviruses include tick- and mosquito-borne viruses that are causes of globally significant emerging diseases. These single-stranded RNA viruses are exquisitely sensitive to the antiviral effects of host interferons. However, both the tick- and mosquitoborne flaviviruses are capable of modulating the interferon response. Despite the high degree of similarity among members of the flavivirus genus, the mechanisms employed by individual viruses to modulate interferon responses differ. This review considers the arthropod-borne flaviviruses and the host interferon response as a pair of forces, the action and the reaction. The interaction of these two forces has led to a complex relationship between virus and host. An increased understanding of these interactions will likely facilitate the rational design of novel vaccines and therapeutics. C1 NIAID, NIH, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Best, SM (reprint author), NIAID, NIH, Rocky Mt Labs, Persistent Viral Dis Lab, 903 So 4th St, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov NR 72 TC 4 Z9 4 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PD JUL PY 2006 VL 1 IS 4 BP 447 EP 459 DI 10.2217/17460794.1.4.447 PG 13 WC Virology SC Virology GA 209ZH UT WOS:000249426000009 ER PT J AU Gonsky, R Deem, RL Bream, JH Young, HA Targan, SR AF Gonsky, R. Deem, R. L. Bream, J. H. Young, H. A. Targan, S. R. TI An IFNG SNP with an estrogen-like response element selectively enhances promoter expression in peripheral but not lamina propria T cells SO GENES AND IMMUNITY LA English DT Article DE human; mucosa; T lymphocytes; cellular activation; transcription factors ID INFLAMMATORY-BOWEL-DISEASE; INTERFERON-GAMMA PROMOTER; GENE-EXPRESSION; IL-2 SECRETION; CD2 PATHWAY; IN-VITRO; TRANSCRIPTION; DIFFERENTIATION; METHYLATION; ACTIVATION AB This study examines mucosa-specific regulatory pathways involved in modulation of interferon-gamma (IFN-gamma) in lamina propria T cells. Previous studies identified mucosa-specific CD2 cis-elements within the -204 to -108 bp IFNG promoter. Within this region, a single-site nucleotide polymorphism, -179G/T, imparts tumor necrosis factor-a stimulation of IFNG in peripheral blood lymphocytes, and is linked with accelerated AIDS progression. We discovered a putative estrogen response element ( ERE) introduced by the -179T which displays selective activation in peripheral blood mononuclear cells (PBMC) vs lamina propria mononuclear cells (LPMC). Transfection of PBMC with constructs containing the -179G or -179T site revealed CD2-mediated enhancement of the -179T compared to -179G allele, although, in LPMC, a similar level of expression was detected. Electrophoretic mobility shift assay ( EMSA) analysis demonstrated CD2-mediated nucleoprotein binding to the -179T but not the -179G in PBMC. In LPMC, binding is constitutive to both -179G and -179T regions. Sequence and EMSA analysis suggests that the -179T allele creates an ERE-like binding site capable of binding recombinant estrogen receptor. Estrogen response element transactivation is enhanced by CD2 signaling, but inhibited by estrogen in PBMC but not in LPMC, although expression of estrogen receptor was similar. This is the first report to describe a potential molecular mechanism responsible for selectively controlling IFN-gamma production in LPMC. C1 Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, Los Angeles, CA 90048 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Dis Prevent & Control Program, Baltimore, MD USA. NCI, Cellular & Mol Immunol Sect, Expt Immunol Lab, Frederick, MD USA. RP Targan, SR (reprint author), Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, 8700 Beverly Blvd,D4063, Los Angeles, CA 90048 USA. EM targans@cshs.org RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 FU NIDDK NIH HHS [DK-43211, DK-46763] NR 40 TC 8 Z9 9 U1 1 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 JUL PY 2006 VL 7 IS 5 BP 342 EP 351 DI 10.1038/sj.gene.6364305 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 067NK UT WOS:000239309700002 PM 16724074 ER PT J AU Angeloni, D ter Elst, A Wei, MH van der Veen, AY Braga, EA Klimov, EA Timmer, T Korobeinikova, L Lerman, MI Buys, CHCM AF Angeloni, Debora ter Elst, Arja Wei, Ming Hui van der Veen, Anneke Y. Braga, Eleonora A. Klimov, Eugene A. Timmer, Tineke Korobeinikova, Luba Lerman, Michael I. Buys, Charles H. C. M. TI Analysis of a new homozygous deletion in the tumor suppressor region at 3p12.3 reveals two novel intronic noncoding RNA genes SO GENES CHROMOSOMES & CANCER LA English DT Article ID CELL LUNG-CANCER; YEAST ARTIFICIAL CHROMOSOMES; CHRONIC LYMPHOCYTIC-LEUKEMIA; SHORT ARM; MICRORNA GENES; LINE U2020; CARCINOMA; LOCUS; IDENTIFICATION; BREAST AB Homozygous deletions or loss of heterozygosity (LOH) at human chromosome band 3p12 are consistent features of lung and other malignancies, suggesting the presence of a tumor suppressor gene(s) (TSG) at this location. Only one gene has been cloned thus far from the overlapping region deleted in lung and breast cancer cell lines U2020, NCI H2198, and HCC38. It is DUTTI (Deleted in U Twenty Twenty), also known as ROBO1, FLJ21882, and SAX3, according to HUGO. DUTTI, the human ortholog of the fly gene ROBO, has homology with NCAM proteins. Extensive analyses of DUTTI in lung cancer have not revealed any mutations, suggesting that another gene(s) at this location could be of importance in lung cancer initiation and progression. Here, we report the discovery of a new, small, homozygous deletion in the small cell lung cancer (SCLC) cell line GLC20, nested in the overlapping, critical region. The deletion was delineated using several polymorphic markers and three overlapping PI phage clones. Fiber-FISH experiments revealed the deletion was approximately 130 kb. Comparative genomic sequence analysis uncovered short sequence elements highly conserved among mammalian genomes and the chicken genome. The discovery of two EST clusters within the deleted region led to the isolation of two noncoding RNA (ncRNA) genes. These were subsequently found differentially expressed in various tumors when compared to their normal tissues. The ncRNA and other highly conserved sequence elements in the deleted region may represent miRNA targets of importance in cancer initiation or progression. Published 2006 Wiley-Liss, Inc.(dagger). C1 NCI, Canc Res Ctr, Immunobiol Lab, Frederick, MD 21701 USA. Univ Groningen, Ctr Med, Dept Med Genet, Groningen, Netherlands. Russian State Genet Ctr, Lab Mol Diagnost, Moscow, Russia. Russian Acad Sci, Lab Comparat Anim Genet, Vavilov Inst Gen Genet, Moscow, Russia. RP Angeloni, D (reprint author), Scuola Super Sant Anna, Via Moruzzi 1, I-56124 Pisa, Italy. EM angeloni@ifc.cnr.it RI Klimov, Eugene/J-2655-2012; Braga, Eleonora/P-5574-2016 OI Klimov, Eugene/0000-0003-2674-5783; NR 65 TC 26 Z9 33 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 2006 VL 45 IS 7 BP 676 EP 691 DI 10.1002/gcc.20332 PG 16 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 042SH UT WOS:000237549200006 PM 16607615 ER PT J AU Annilo, T Chen, ZQ Shulenin, S Costantino, J Thomas, L Lou, H Stefanov, S Dean, M AF Annilo, T Chen, ZQ Shulenin, S Costantino, J Thomas, L Lou, H Stefanov, S Dean, M TI Evolution of the vertebrate ABC gene family: Analysis of gene birth and death SO GENOMICS LA English DT Article DE ATP-binding cassette; transporter; evolution; lipid transport; drug resistance; cystic fibrosis; adrenoleukodystrophy ID BINDING CASSETTE TRANSPORTER; MULTIDRUG-RESISTANCE; DIETARY-CHOLESTEROL; MUTATIONS; GENOME; DUPLICATION; ZEBRAFISH; MODEL; IDENTIFICATION; SUPERFAMILY AB Vertebrate evolution has been largely driven by the duplication of genes that allow for the acquisition of new functions. The ATP-binding cassette (ABC) proteins constitute a large and functionally diverse family of membrane transporters. The members of this multigene family are found in all cellular organisms, most often engaged in the translocation of a wide variety of substrates across lipid membranes. Because of the diverse function of these genes, their large size, and the large number of orthologs, ABC genes represent an excellent tool to study gene family evolution. We have identified ABC proteins from the sea squirt (Ciona intestinalis), zebrafish (Danio rerio), and chicken (Gallus gallus) and, using phylogenetic analysis, identified those genes with a one-to-one orthologous relationship to human ABC proteins. All ABC protein subfamilies found in Ciona and zebrafish correspond to the human subfamilies, with the exception of a single ABCH subfamily gene found only in zebrafish. Multiple gene duplication and deletion events were identified in different lineages, indicating an ongoing process of gene evolution. As many ABC genes are involved in human genetic diseases, and important drug transport phenotypes, the understanding of ABC gene evolution is important to the development of animal models and functional studies. Published by Elsevier Inc. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Basic Res Program, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Bldg 560,Room 21-18, Frederick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012; Annilo, Tarmo/J-2900-2013 OI Dean, Michael/0000-0003-2234-0631; Annilo, Tarmo/0000-0002-9588-3058 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-124000]; Wellcome Trust [070191/Z/03/Z] NR 41 TC 82 Z9 87 U1 0 U2 11 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 JUL PY 2006 VL 88 IS 1 BP 1 EP 11 DI 10.1016/j.ygeno.2006.03.001 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 056VD UT WOS:000238552300001 PM 16631343 ER PT J AU Lee, TL Alba, D Baxendale, V Rennert, OM Chan, WY AF Lee, TL Alba, D Baxendale, V Rennert, OM Chan, WY TI Application of transcriptional and biological network analyses in mouse germ-cell transcriptomes SO GENOMICS LA English DT Article DE spermatogenesis; germ cell development; SAGE; systems biology ID DIFFERENTIALLY EXPRESSED GENES; NF-KAPPA-B; SPERMATOGENIC CELLS; SYSTEMS BIOLOGY; SERIAL ANALYSIS; MESSENGER-RNA; TESTIS; MICE; IDENTIFICATION; PROTEIN AB Serial analysis of gene expression (SAGE) provides a global analysis platform for profiling mRNA populations present in cells of interest without the constraint of gene selection and the ambiguous nature of data obtained. However, most of the reports on SAGE and germ cell development are limited to descriptive analyses. Here, we report a series of bioinformatic analyses using recently published SAGE data on the transcriptome of mouse type A spermatogonia (Spga), pachytene spermatocytes (Spcy), and round spermatids (Sptd). Tags with a total count of 20 in three SAGE libraries were examined. Our aim was to identify and discover potential transcriptional regulators and pathways involved at different stages of spermatogenesis. Unsupervised hierarchical clustering based on tag expression and Gene Ontology analysis were applied to identify genes and biological processes overrepresented at a particular stage of development. The 5' cis-regulatory elements were examined for common regulators in different functional clusters. Potential biological networks were also constructed to reveal the link between the gene candidates. Biological pathways related to the three germ cell stages were constructed. A number of known transcription regulators in spermatogenesis, including NF-kappa B, SP1, AP-1, and EGR, were identified. Novel promoter elements such as the E box in Spga-specific genes, GATA in Spcy-specific genes, and GKLF in Sptd-specific genes were also observed. Taken together, our approach is reliable and provides a foundation for the generation of novel biological hypotheses for studying spermatogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. RP Lee, TL (reprint author), NICHHD, Lab Clin Genom, NIH, Bldg 49,Room 2C08,49 Convent Dr,MSC 4429, Bethesda, MD 20892 USA. EM leetl@mail.nih.gov RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU Intramural NIH HHS NR 56 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2006 VL 88 IS 1 BP 18 EP 33 DI 10.1016/j.ygeno.2006.03.008 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 056VD UT WOS:000238552300003 PM 16678385 ER PT J AU Bondy, CA Bakalov, VK AF Bondy, Carolyn A. Bakalov, Vladimir K. TI Investigation of cardiac status and bone mineral density in Turner syndrome SO GROWTH HORMONE & IGF RESEARCH LA English DT Article; Proceedings Paper CT 19th Annual National Cooperative Growth Study/1st Annual National Cooperative Metabolic Study Investigator Meeting CY NOV 03-05, 2005 CL San Francisco, CA DE magnetic resonance angiography; congenital heart defects; osteoporosis; X-chromosome; SHOX ID GROWTH-HORMONE; YOUNG-WOMEN; MORTALITY; ABSORPTIOMETRY; ABNORMALITIES; REPLACEMENT; ALENDRONATE; PREVALENCE; DEFICIENCY; ESTROGEN AB This review highlights recent developments in the detection and management of congenital heart disease and osteoporosis in patients with monosomy X, or Turner syndrome (TS). Magnetic resonance angiography (MRA) using gadolinium as a contrast agent demonstrates a higher prevalence and greater diversity of congenital cardiovascular defects than previously recognized in TS. Almost 50% of girls and women with TS have marked tortuosity or ectasia of the aortic arch, suggesting that these individuals may be at greater risk for aneurysm formation or dissection and therefore require closer monitoring. MRA also reveals that major venous anomalies are common in TS, with partial anomalous pulmonary venous return and persistent left superior vena cava each found in about 13% of patients. MR imaging even without contrast is a valuable complement to routine cardiac ultrasound in detecting abnormalities of the aortic valve. Abnormal electrocardiographic findings, including prolongation of the QTc interval, have recently been documented in many individuals with TS. Conduction and repolarization abnormalities have not been associated with congenital anatomic defects and are as common in young girls as adults. The clinical significance of these electrophysiological findings is unknown at present, but attention to the ECG in TS is important, particularly in monitoring the QTc when prescribing drugs associated with QT prolongation. Patients with TS are at high risk for osteoporosis as a result of premature ovarian failure and intrinsic bone abnormalities specific to the syndrome. Low cortical bone mineral density (BMD) is apparent in prepubertal girls, and it remains low in adults, independent of estrogen treatment and other hormonal factors. The low mineralization of cortical bone in TS may be associated with a small increased fracture risk, but no treatments are known to increase cortical bone mineral content in TS. Trabecular BMD is normal in TS women who have received continuous estrogen treatment from their mid-teens, although areal densitometry scores may be misleadingly low in very small patients. However, young women with ovarian failure who have not received estrogen treatment for extended periods of time are at high risk for osteoporosis of trabecular bone of the spine, with associated compression fractures and height loss. Therefore, judicious management of estrogen therapy to prevent osteoporosis while minimizing estrogen-associated adverse events is a challenging aspect of care for girls and women with TS. (c) 2006 Elsevier Ltd. All rights reserved. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, CRC I-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 42 TC 5 Z9 5 U1 0 U2 0 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 JUL PY 2006 VL 16 SU A BP S103 EP S108 DI 10.1016/j.ghir.2006.03.008 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 074OG UT WOS:000239821100017 PM 16624607 ER PT J AU Berger, VW AF Berger, Vance W. TI Misguided precedent is not a reason to use permuted blocks SO HEADACHE LA English DT Letter ID RANDOMIZATION C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD JUL-AUG PY 2006 VL 46 IS 7 BP 1210 EP 1212 DI 10.1111/j.1526-4610.2006.00517_2.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 059RA UT WOS:000238748700027 PM 16866731 ER PT J AU Fuemmeler, BF Masse, LC Yaroch, AL Resnicow, K Campbell, MK Carr, C Wang, T Williams, A AF Fuemmeler, Bernard F. Masse, Louise C. Yaroch, Amy L. Resnicow, Ken Campbell, Marci Kramish Carr, Carol Wang, Terry Williams, Alexis TI Psychosocial mediation of fruit and vegetable consumption in the body and soul effectiveness trial SO HEALTH PSYCHOLOGY LA English DT Article DE mediation analysis; African American; fruits and vegetables; randomized controlled trial; latent variable structural equation modeling ID PHYSICAL-ACTIVITY INTERVENTION; FOOD-FREQUENCY QUESTIONNAIRE; NUTRITION INTERVENTION; BLACK CHURCHES; SOCIAL SUPPORT; DIETARY CHANGE; SMOKING CESSATION; HEALTH PROJECT; PREVENTION; BEHAVIORS AB In this study the authors examined psychosocial variables as mediators for fruit and vegetable (FV) intake in a clustered, randomized effectiveness trial conducted in African American churches. The study sample included 14 churches (8 intervention and 6 control) with 470 participants from the intervention churches and 285 participants from the control churches. The outcome of FV intake and the proposed mediators were measured at baseline and at 6-month follow-up. Structural equation modeling indicated that the intervention had direct effects on social support, self-efficacy, and autonomous motivation; these variables also had direct effects on FV intake. Applying the M. E. Sobel (1982) formula to test significant mediated effects, the authors confirmed that social support and self-efficacy were significant mediators but that autonomous motivation was not. Social support and self-efficacy partially mediated 20.9% of the total effect of the intervention on changes in FV intake. The results support the use of strategies to increase social support and self-efficacy in dietary intervention programs. C1 NCI, Hlth Promot Res Branch, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Fuemmeler, BF (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, DUMC 2914, Durham, NC 27710 USA. EM bernard.fuemmeler@duke.edu RI Campbell, Michelle/B-5793-2008 NR 52 TC 55 Z9 56 U1 5 U2 10 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2006 VL 25 IS 4 BP 474 EP 483 DI 10.1037/0278-6133.25.4.474 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 065SL UT WOS:000239179500004 PM 16846322 ER PT J AU Miller-Davis, C Marden, S Leidy, NK AF Miller-Davis, Claiborne Marden, Sue Leidy, Nancy Kline TI The New York Heart Association Classes and functional status: What are we really measuring? SO HEART & LUNG LA English DT Article ID QUALITY-OF-LIFE; CONTROLLED-TRIAL; CARDIAC RESYNCHRONIZATION; VALVE-REPLACEMENT; ELDERLY-PATIENTS; FAILURE; DISEASE; EFFICACY; CLASSIFICATION; QUESTIONNAIRE AB The New York Heart Association (NYHA) Classes are used to appraise the status of patients with heart disease and evaluate treatment outcomes in clinical and research settings. Ambiguity exists concerning the construct the Classes represent and the optimal way to capture and interpret the information. This article examines the NYHA Classes within the context of a published functional status framework by Leidy. The framework proposes that (1) physiological indicators provide information on capacity, (2) physical activity characterizes performance, and (3) symptoms accompanying activity offer insight into reserve. It is proposed that the NYHA Classes provide a summary statement of both the reduction in reserve accompanying a decline in capacity and the concomitant increase in capacity utilization required to maintain performance in patients with heart disease. This premise is illustrated quantitatively through secondary analysis of data from 22 patients with ischemic heart disease and left ventricular dysfunction. C1 NIH, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. United BioSource Corp, Hlth Care Analyt Grp, Bethesda, MD USA. RP Miller-Davis, C (reprint author), NIH, Mark O Hatfield Clin Res Ctr, 10 Ctr Dr,Room 8N223, Bethesda, MD 20892 USA. NR 38 TC 13 Z9 17 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 2006 VL 35 IS 4 BP 217 EP 224 DI 10.1016/j.hrtlng.2006.01.003 PG 8 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 070LC UT WOS:000239522900001 PM 16863893 ER PT J AU Reshamwala, PA Kleiner, DE Heller, T AF Reshamwala, PA Kleiner, DE Heller, T TI Nodular regenerative hyperplasia: Not all nodules are created equal SO HEPATOLOGY LA English DT Article ID NONCIRRHOTIC PORTAL-HYPERTENSION; PRIMARY BILIARY-CIRRHOSIS; EARLY HISTOLOGICAL STAGES; OF-THE-LITERATURE; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; PHARMACOLOGICAL-TREATMENT; AZATHIOPRINE; PATHOGENESIS; DIAGNOSIS C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Med Ctr, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA. RP Heller, T (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. EM theoh@intra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 46 TC 94 Z9 101 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 JUL PY 2006 VL 44 IS 1 BP 7 EP 14 DI 10.1002/hep.21258 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 058UU UT WOS:000238690900003 PM 16799965 ER PT J AU Shen, M Zheng, TZ Lan, Q Zhang, YW Zahm, SH Wang, SS Holford, TR Leaderer, B Yeager, M Welch, R Kang, D Boyle, P Zhang, B Zou, KY Zhu, Y Chanock, S Rothman, N AF Shen, M Zheng, TZ Lan, Q Zhang, YW Zahm, SH Wang, SS Holford, TR Leaderer, B Yeager, M Welch, R Kang, D Boyle, P Zhang, B Zou, KY Zhu, Y Chanock, S Rothman, N TI Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut SO HUMAN GENETICS LA English DT Article ID WERNER-SYNDROME PROTEIN; LUNG-CANCER; XPG; CELLS; RECOMBINATION; EPIDEMIOLOGY; POPULATION; MECHANISMS; EXPRESSION; PATHWAYS AB Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case-control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13-1.88; P = 0.004), DLBCL (OR: 1.44; 95% CI: 0.99-2.09; P = 0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56-0.91; P = 0.007) and DLBCL (OR: 0.66; 95% CI: 0.45-0.95; P = 0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Int Agcy Res Canc, F-69372 Lyon, France. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Shen, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI Kang, Dae Hee/E-8631-2012; Boyle, Peter/A-4380-2014; Zahm, Shelia/B-5025-2015 OI Boyle, Peter/0000-0001-6251-0610; FU Intramural NIH HHS; NCI NIH HHS [CA62006] NR 35 TC 65 Z9 69 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2006 VL 119 IS 6 BP 659 EP 668 DI 10.1007/s00439-006-0177-2 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 049KN UT WOS:000238015200009 PM 16738949 ER PT J AU Bernat, JA Crawford, GE Ogurtsov, AY Collins, FS Ginsburg, D Kondrashov, AS AF Bernat, John A. Crawford, Gregory E. Ogurtsov, Aleksey Y. Collins, Francis S. Ginsburg, David Kondrashov, Alexey S. TI Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs SO HUMAN MOLECULAR GENETICS LA English DT Article ID ETS TRANSCRIPTION FACTORS; WILLEBRAND-FACTOR GENE; LOCUS-CONTROL REGIONS; INTERGENIC REGIONS; IN-VIVO; MOUSE; GENOME; EXPRESSION; CHROMATIN; ENHANCER AB The transcriptional regulation of genes is a complex process, particularly for genes exhibiting a tissue-specific pattern of expression. We studied 28 genes that are expressed primarily in endothelial cells, another 28 genes that are expressed highly, but not exclusively, in cultured endothelial cells, and three control sets, consisting of genes not expressed in endothelium, genes expressed in neural tissues and housekeeping genes. For each gene, we identified conserved non-coding sequences (CNSs) of lengths 50 to > 1000 nucleotides, located within the upstream intergenic region (from 500 to as far as 200 000 nucleotides upstream from the transcription start) or within the first intron. As a functional test, we assayed the CNSs from the set of endothelial cell-specific genes (EC-CNSs) for DNase hypersensitivity. Among 262 distant EC-CNSs, 33% are hypersensitive (HS) in endothelial cells, whereas only 16% are HS in control fibroblasts. A search for short sequence patterns revealed a number of motifs which are over-represented in EC-CNSs relative to CNSs from the control gene sets. In particular, the motif SAGGAAR is strongly and consistently over-represented among EC-CNSs, and is more over-represented in HS CNSs than in non-HS CNSs. CNSs which contain this motif are no closer to the promoter than an average CNS. This motif contains the core element of binding sites from the Ets family of transcription factors. Thus, one or several factors from this family may play a key role in the regulation of endothelial gene expression. C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Ginsburg, D (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. EM ginsburg@umich.edu FU NCI NIH HHS [5 P30 CA46592]; NHLBI NIH HHS [R37-HL39693, P01 HL057346] NR 32 TC 15 Z9 15 U1 0 U2 1 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 JUL 1 PY 2006 VL 15 IS 13 BP 2098 EP 2105 DI 10.1093/hmg/ddl133 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 056PN UT WOS:000238537700007 PM 16723375 ER PT J AU Durbin, AP McArthur, J Marron, JA Blaney, JE Thumar, B Wanionek, K Murphy, BR Whitehead, SS AF Durbin, Anna P. McArthur, Julie Marron, Jennifer A. Blaney, Joseph E., Jr. Thumar, Bhavin Wanionek, Kim Murphy, Brian R. Whitehead, Stephen S. TI The live attenuated dengue serotype 1 vaccine rDEN1 Delta 30 is safe and highly immunogenic in healthy adult volunteers SO HUMAN VACCINES LA English DT Article DE live attenuated dengue serotype 1 vaccine ID SECONDARY STRUCTURE; RHESUS-MONKEYS; VIRUS TYPE-4; 3'-UNTRANSLATED REGION; UNTRANSLATED REGION; ANTIBODY-RESPONSE; DISEASE SEVERITY; CELL-CULTURE; CANDIDATE; FORMULATIONS AB Background: The live attenuated DEN 1 vaccine candidate virus rDEN1 Delta 30 has been evaluated in preclinical animal models and found to be attenuated and immunogenic. These promising preclinical studies have identified rDEN1 Delta 30 as a candidate DEN] vaccine virus for further testing in a human Phase I clinical trial. Methods: rDEN1 Delta 30 at a dose of 10(3) pfu was administered as a single inoculation to twenty healthy adult volunteers. Eight additional volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected on study days 0, 28, 42 and 180 for determination of neutralizing antibody titer. Results: The vaccine was well tolerated by the vaccinees. The most common adverse events observed were a transient asymptomatic rash in 40% of vaccinees and a mild neutropenia in 45% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic with 95% of vaccinees developing a >= 4-fold rise in serum neutralizing antibody titer against DEN1 that persisted throughout the six month duration of the trial. Conclusions: The rDEN1 Delta 30 vaccine is safe and induced a potent and durable antibody response against DEN1. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD 21218 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, 624 N Broadway,Room 214, Baltimore, MD 21218 USA. EM adurbin@jhsph.edu FU Intramural NIH HHS NR 42 TC 67 Z9 70 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8600 J9 HUM VACCINES JI Hum. Vaccines PD JUL-AUG PY 2006 VL 2 IS 4 BP 167 EP 173 PG 7 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 132YV UT WOS:000243979700004 PM 17012875 ER PT J AU McCreedy, ES Cheng, RD Hemler, PF Viswanathan, A Wood, BJ McAuliffe, MJ AF McCreedy, Evan S. Cheng, Ruida Hemler, Paul F. Viswanathan, Anand Wood, Bradford J. McAuliffe, Matthew J. TI Radio frequency ablation registration, segmentation, and fusion tool SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article; Proceedings Paper CT 18th IEEE Symposium on Computer-Based Medical Systems CY JUN 23-24, 2005 CL Dublin, IRELAND SP IEEE Comp Soc Tech Comm Computat Med, Trinity Coll Dublin, Dept Comp Sci, Sci Fdn Ireland DE ablation; biomedical image processing; blood vessels; image analysis; image registration; image segmentation; liver; medical decision making; rendering (computer graphics) ID GAMMA-KNIFE RADIOSURGERY; BRAIN IMAGES; OPTIMIZATION AB The radio frequency ablation segmentation tool (RFAST) is a software application developed using the National Institutes of Health's medical image processing analysis and visualization (MIPAV) API for the specific purpose of assisting physicians in the planning of radio frequency ablation (RFA) procedures. The RFAST application sequentially leads the physician through the steps necessary to register, fuse, segment, visualize, and plan the RFA treatment. Three-dimensional volume visualization of the CT dataset with segmented three dimensional (3-D) surface models enables the physician to interactively position the ablation probe to simulate burns and to semimanually simulate sphere packing in an attempt to optimize probe placement. This paper describes software systems contained in RFAST to address the needs of clinicians in planning, evaluating, and simulating RFA treatments of malignant hepatic tissue. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Hampden Sydney Coll, Hampden Sydney, VA 23943 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP McCreedy, ES (reprint author), NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. EM mccreedy@mail.nih.gov OI Viswanathan, Anand/0000-0003-3810-6217 FU Intramural NIH HHS [Z99 CL999999] NR 20 TC 12 Z9 13 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1089-7771 EI 1558-0032 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD JUL PY 2006 VL 10 IS 3 BP 490 EP 496 DI 10.1109/TITB.2006.872076 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 063PW UT WOS:000239033000009 PM 16871716 ER PT J AU Broussard, C Fleischecker, C Horai, R Chetana, M Venegas, AM Sharp, LL Hedrick, SM Fowlkes, BJ Schwartzberg, PL AF Broussard, Christine Fleischecker, Christine Horai, Reiko Chetana, Madeva Venegas, Ana M. Sharp, Leslie L. Hedrick, Stephen M. Fowlkes, B. J. Schwartzberg, Pamela L. TI Altered development of CD8(+) T cell lineages in mice deficient for the Tec kinases Itk and Rlk SO IMMUNITY LA English DT Article ID DOUBLE-POSITIVE THYMOCYTES; CLASS-I MOLECULES; CUTTING EDGE; HISTOCOMPATIBILITY ANTIGEN; HEMATOPOIETIC-CELLS; NEGATIVE SELECTION; FAMILY KINASES; COMMITMENT; RECEPTOR; PROTEIN AB Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk(-/-) and Rlk(-/-) Itk(-/-) mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8(+) T cells in these mice do not resemble conventional CD8(+) T cells. Instead, these cells express memory markers, rapidly produce interferon-gamma, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted "innate-type" lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8(+) T cell phenotypes in Itk(-/-) mice, arguing that altered signaling permits development of this innate-type CD8(+) cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes. C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM pams@nhgri.nih.gov FU Intramural NIH HHS NR 57 TC 128 Z9 129 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2006 VL 25 IS 1 BP 93 EP 104 DI 10.1016/j.immuni.2006.05.011 PG 12 WC Immunology SC Immunology GA 072ZX UT WOS:000239713000013 PM 16860760 ER PT J AU Sidney, J Asabe, S Peters, B Purton, KA Chung, J Pencille, TJ Purcell, R Walker, CM Chisari, FV Sette, A AF Sidney, John Asabe, Shinichi Peters, Bjoern Purton, Kelly-Anne Chung, Josan Pencille, Timothy J. Purcell, Robert Walker, Christopher M. Chisari, Francis V. Sette, Alessandro TI Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules SO IMMUNOGENETICS LA English DT Article DE major histocompatibility complex; epitopes; antigen presentation ID VIRUS NUCLEOCAPSID ANTIGEN; SECONDARY ANCHOR RESIDUES; CYTOTOXIC T-LYMPHOCYTES; ACUTE HEPATITIS; HLA-A; REPERTOIRES; EPITOPES; CELLS; INFECTION; CHIMPANZEES AB The chimpanzee (Pan troglodytes) is an important model for studying the immune response to several human pathogens, but the study of correlates of immunity has been hindered by the fact that little is known about the epitope-binding specificity of chimpanzee (Patr) class I MHC. In the present study we have characterized the peptide binding specificity of several common Patr class I molecules. Using single amino acid substitution analogs and large peptide libraries, quantitative peptide binding motifs have been derived for Patr A*0101, A*0701, A*0901, B*0101, and B*2401. Each molecule was found to bind peptides using position 2 and the C terminus as main anchor contacts. On the other hand, each Patr molecule is associated with a unique binding specificity, and the range of specificities is similar to that seen amongst HLA alleles. A high degree of cross-reactivity was noted between Pair A*0701 and Patr A*0901, suggesting the existence of a Patr-specific supertype. Consistent with previous studies suggesting that some cross-reactivity may exist between HLA and Patr alleles, Patr A*0901 was found to have an appreciable degree of cross-reactivity with molecules of the HLA A24-supertype. Finally, utilizing motif scans and peptide binding and intracellular cytokine staining assays, 77 hepatitis B virus (HBV)-derived epitopes were identified in five chimpanzees that were recently convalescent from acute HBV infection. Because the Patr alleles studied herein were found to be very common in two different chimpanzee populations, the present data should facilitate the use of chimpanzees for immunological studies. C1 La Jolla Inst Allergy & Immunol, San Diego, CA 92109 USA. Scripps Res Inst, La Jolla, CA 92037 USA. NIAID, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Childrens Res Inst, Columbus, OH USA. RP Sette, A (reprint author), La Jolla Inst Allergy & Immunol, 3030 Bunker Hill St,Ste 326, San Diego, CA 92109 USA. EM alex@liai.org RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU NCI NIH HHS [R01-CA76403]; NIAID NIH HHS [N01-AI-40023, N01-AI-40024, R01-AI20001] NR 29 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUL PY 2006 VL 58 IS 7 BP 559 EP 570 DI 10.1007/s00251-006-0131-4 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 074NF UT WOS:000239818400006 PM 16791621 ER PT J AU Moayeri, M Wickliffe, KE Wiggins, JF Leppla, SH AF Moayeri, M Wickliffe, KE Wiggins, JF Leppla, SH TI Oxidized ATP protection against anthrax lethal toxin SO INFECTION AND IMMUNITY LA English DT Article ID PURINERGIC P2Z RECEPTOR; EXTRACELLULAR ATP; DIPHTHERIA-TOXIN; P2X(7) RECEPTOR; H+-ATPASE; ADENOSINE 5'-TRIPHOSPHATE; MACROPHAGE SENSITIVITY; SARCOPLASMIC-RETICULUM; ADENYLATE-CYCLASE; PLASMA-MEMBRANE AB Bacillus anthracis lethal toxin (LT) induces rapid lysis (< 90 min) of murine macrophages from certain inbred strains. The mechanism for LT-induced cytolysis is currently unknown. We hypothesized that the ATP-activated macrophage P2X7 receptors implicated in nucleotide-mediated macrophage lysis could play a role in LT-mediated cytolysis and discovered that a potent P2X7 antagonist, oxidized ATP (o-ATP), protects macrophages against LT. Other P2X7 receptor antagonists, however, had no effect on LT function, while oxidized nucleotides, o-ADP, o-GTP, and o-ITP, which did not act as receptor ligands, provided protection. Cleavage of the LT substrates, the mitogen-activated protein kinases, was inhibited by o-ATP in RAW274.6 macrophages and CHO cells. We investigated the various steps in the intoxication pathway and found that binding of the protective-antigen (PA) component of LT to cells and the enzymatic proteolytic ability of the lethal factor (LF) component of LT were unaffected by o-ATP. Instead, the drug inhibited formation of the sodium dodecyl sulfate-resistant PA oligomer, which occurs in acidified endosomes, but did not prevent cell surface PA oligomerization, as evidenced by binding and translocation of LF to a protease-resistant intracellular location. We found that o-ATP also protected cells from anthrax edema toxin and diphtheria toxin, which also require an acidic environment for escape from endosomes. Confocal microscopy using pH-sensitive fluorescent dyes showed that o-ATP increased endosomal pH. Finally, BALB/cJ mice injected with o-ATP and LT were completely protected against lethality. C1 NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Microbial Pathogenesis Sect, NIH, Bldg 30,Room 303, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural NIH HHS NR 59 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2006 VL 74 IS 7 BP 3707 EP 3714 DI 10.1128/IAI.00051-06 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 057JJ UT WOS:000238591800002 PM 16790743 ER PT J AU Pinheiro, NF Hermida, MDR Macedo, MP Mengel, J Bafica, A dos-Santos, WLC AF Pinheiro, NF Hermida, MDR Macedo, MP Mengel, J Bafica, A dos-Santos, WLC TI Leishmania infection impairs beta(1)-integrin function and chemokine receptor expression in mononuclear phagocytes SO INFECTION AND IMMUNITY LA English DT Article ID DENDRITIC CELLS; COSTIMULATORY MOLECULES; VISCERAL LEISHMANIASIS; ADHESION MOLECULES; T-CELL; INTEGRIN ACTIVATION; LANGERHANS CELLS; LYMPH-NODE; MACROPHAGES; CC AB Leishmania spp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown that Leishmania infection reduces mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we examined the role of adhesion molecules and chemokines in this process. Infection rate (r = -0.826, P = 0.003) and parasite burden (r = -0.917, P = 0.028) negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0% inhibition, P = 0.005) in phagocyte adhesion to connective tissue, induced by Leishmania, occurred as early as 2 h after infection and was maintained for at least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte infection, since it was not observed following phagocytosis of killed parasites (cell adhesion varied from 15.2% below to 24.0% above control levels, P > 0.05). In addition, Leishmania infection diminished cell adhesion to fibronectin (54.1 to 96.2%, P < 0.01), collagen (15.7 to 83.7%, P < 0.05), and laminin (59.1 to 82.2%, P < 0.05). The CD11b(hi) subpopulation was highly infected (49.6 to 97.3%). Calcium and Mg2+ replacement by Mn2+, a treatment that is known to induce integrins to a high state of affinity for their receptors, reverted the inhibition in adhesion caused by Leishmania. This reversion was completely blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively). Together, these results suggest that mechanisms regulating integrin function are implicated in the change of macrophage adhesion in leishmaniasis. C1 Fdn Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, LPBI, BR-40296710 Salvador, BA, Brazil. Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP dos-Santos, WLC (reprint author), Fdn Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, LPBI, Rua Waldemar Falcao 121, BR-40296710 Salvador, BA, Brazil. EM wluis@cpqgm.fiocruz.br RI Hermida, Micely/B-4710-2009; DOS-SANTOS, WASHINGTON/B-4173-2009 OI DOS-SANTOS, WASHINGTON/0000-0003-1445-2318 NR 55 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2006 VL 74 IS 7 BP 3912 EP 3921 DI 10.1128/IAI.02103-05 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 057JJ UT WOS:000238591800023 PM 16790764 ER PT J AU Chang, YC Jong, A Huang, S Zerfas, P Kwon-Chung, KJ AF Chang, YC Jong, A Huang, S Zerfas, P Kwon-Chung, KJ TI CPS1, a homolog of the Streptococcus pneumoniae type 3 polysaccharide synthase gene, is important for the pathobiology of Cryptococcus neoformans SO INFECTION AND IMMUNITY LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; CAPSULE-ASSOCIATED GENE; BLOOD-BRAIN-BARRIER; IN-VITRO; VIRULENCE; HYALURONAN; YEAST; BIOSYNTHESIS; PROTEINS; PATHWAY AB The polysaccharide capsule is known to be the major factor required for the virulence of Cryptococcus neoformans. We have cloned and characterized a gene, designated CPS1, that encodes a protein containing a glycosyltransferase moiety and shares similarity with the type 3 polysaccharide synthase encoded by the cap3B gene of Streptococcus pneumoniae. Cps1p also shares similarity with hyaluronan synthase of higher eukaryotes. Deletion of the CPS1 gene from a serotype D strain of C. neoformans resulted in a slight reduction of the capsule size as observed by using an India ink preparation. The growth at 37 degrees C was impaired, and the ability to associate with human brain endothelial cells in vitro was also significantly reduced by the deletion of CPS1. Using site-specific mutagenesis, we showed-that the conserved glycosyltransferase domains are critical for the ability of the strain to grow at elevated temperatures. A hyaluronan enzyme-linked immunosorbent assay method demonstrated that CPS1 is important for the synthesis of hyaluronan or its related polysaccharides in C. neoformans. Comparisons between the wild-type and the cps1 Delta strains, using three different transmission electron microscopic methods, indicated that the CPS1 gene product is involved in the composition or maintenance of an electron-dense layer between the outer cell wall and the capsule. These and the virulence studies in a mouse model suggested that the CPS1 gene is important in the pathobiology of C. neoformans. C1 NIAID, LCID, NIH, Bethesda, MD 20892 USA. Univ So Calif, Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA USA. NIH, Div Vet Resources, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, LCID, NIH, Bldg 10,Rm 11C304, Bethesda, MD 20892 USA. EM June_Kwon_Chung@nih.gov FU Intramural NIH HHS NR 31 TC 34 Z9 38 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2006 VL 74 IS 7 BP 3930 EP 3938 DI 10.1128/IAI.00089-06 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 057JJ UT WOS:000238591800025 PM 16790766 ER PT J AU Calvo, E Pham, VM Lombardo, F Arca, B Ribeiro, JMC AF Calvo, Eric Pham, Van M. Lombardo, Fabrizio Arca, Bruno Ribeiro, Jose M. C. TI The sialotranscriptome of adult male Anopheles gambiae mosquitoes SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE salivary glands; sugar feeding; mosquito; antimicrobial; sialome ID SALIVARY-GLAND; FEMALE MOSQUITO; AEDES-AEGYPTI; PSI-BLAST; DATABASE; TRANSCRIPTOME; STATISTICS; EVOLUTION; ALIGNMENT; PROTEINS AB Adult mosquitoes feed on sugary meals to obtain energy for flight and other activities, while anautogenous females take a blood meal to develop eggs. Accordingly, female but not male salivary glands possess several antihemostatic components to facilitate acquisition of blood, while both sexes have activities related to digestion of the sugar meal as well as antimicrobials to maintain meal integrity. Studies on adult female sialotranscriptomes indicated a set of similar to 70 proteins and peptides possibly secreted in saliva that presumably facilitate sugar and blood meals. Most of these proteins have no known function, so no assignment to blood or sugar feeding is possible. Microarray and RT-PCR studies attempted to identify sex specificity of these transcripts. Our present study complements the previous data set, comparing similar to 1000 randomly sequenced clones of a male adult salivary gland cDNA library with the female set. Statistically significant differences were found in 16 transcripts found exclusively in the female library, 4 transcripts significantly female enriched but also found in male glands, and 6 transcripts enriched in male glands. We additionally found a transcript in male salivary glands with a trypsin inhibitor-like (TIL) domain that we presume codes for an antimicrobial peptide; a novel defensin transcript was also found in the male sialotranscriptome. Supplemental tables can be found at http://www.ncbi.nlm.nih.gov/projects/omes/ Published by Elsevier Ltd. C1 NIAID, Sect Vector Biol, Lab Malaria & Vector Res, Rockville, MD 20852 USA. Univ Roma La Sapienza, Parasitol Sect, Dept Publ Hlth, I-00185 Rome, Italy. Univ Naples Federico II, Dept Struct & Funct Biol, I-80126 Naples, Italy. RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 2E-32D, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov RI Lombardo, Fabrizio/J-8511-2014; OI Lombardo, Fabrizio/0000-0002-8563-0612; Arca, Bruno/0000-0002-4029-0984; Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS NR 30 TC 32 Z9 35 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JUL PY 2006 VL 36 IS 7 BP 570 EP 575 DI 10.1016/j.ibmb.2006.04.005 PG 6 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 071PS UT WOS:000239614700005 PM 16835022 ER PT J AU Waalkes, MP Liu, J Kasprzak, KS Diwan, BA AF Waalkes, MP Liu, J Kasprzak, KS Diwan, BA TI Hypersusceptibility to cisplatin carcinogenicity in metallothionein-I/II double knockout mice: Production of hepatocellular carcinoma at clinically relevant doses SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cisplatin; carcinogenesis; mice; metallothionein ID RENAL TOXICITY; CIS-DIAMMINEDICHLOROPLATINUM; PROTECTIVE ROLE; MESSENGER-RNA; KIDNEY; MOUSE; ZINC; EXPRESSION; RESISTANCE; INDUCTION AB Metallothionein (MT) is a high-affinity metal binding protein thought to mitigate the toxicity of various metals. Cisplatin is a widely used cancer chemotherapeutic that is a rodent carcinogen and may have carcinogenic potential in humans. MT seems to reduce cisplatin toxicity by binding the metal compound but how MT deficiency might impact the carcinogenic effects of cisplatin Is unknown. Thus, groups (it = 25) of male MT-I/II double knockout (MT-null) or MT wild-type (WT) mice were exposed to a single treatment of cisplatin (5 or 10 mg/kg, i.p.), or left untreated (control) and observed over the next 104 weeks. The doses of cisplatin used equate to only a fraction of the total dose used typically in clinical settings. In cisplatin-treated MT-null mice, a dose-related increase in hepatocellular carcinoma (HCC) occurred (control, 0%; 5 mg/kg, 17%; 10 mg/kg, 36%) that was not seen in WT mice. Similarly, liver carcinoma multiplicity (HCC/liver) was increased markedly by cisplatin but only in MT-null mice, indicating the formation of multiple primaries in MT deficient mice. Harderian gland carcinoma incidence was also increased by cisplatin treatment in MT-null mice but not WT mice. Our results indicate that MT-null mice are hypersusceptible to the hepatocarcinogenic effects of cisplatin, and poor NIT expression may be a predisposing factor for cisplatin-induced secondary tumors after chemotherapy. (c) 2006 Wiley-Liss, Inc. C1 NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC 27709 USA. NCI, Met Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21701 USA. RP Waalkes, MP (reprint author), NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIEHS, 111 Alexander Dr,POB 1223,MD F0-09, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 43 TC 23 Z9 25 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 JUL 1 PY 2006 VL 119 IS 1 BP 28 EP 32 DI 10.1002/ijc.21245 PG 5 WC Oncology SC Oncology GA 041CH UT WOS:000237430200004 PM 16432836 ER PT J AU Rahu, M Rahu, K Auvinen, A Tekkel, M Stengrevics, A Hakulinen, T Boice, JD Inskip, PD AF Rahu, M Rahu, K Auvinen, A Tekkel, M Stengrevics, A Hakulinen, T Boice, JD Inskip, PD TI Cancer risk among Chernobyl cleanup workers in Estonia and Latvia, 1986-1998 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE neoplasms; incidence; cohort; Chernobyl; Estonia; Latvia; radiation effects ID POWER INDUSTRY WORKERS; LOW-DOSE EXPOSURE; IONIZING-RADIATION; EMERGENCY WORKERS; THYROID-CANCER; EPIDEMIOLOGIC RESEARCH; NUCLEAR WORKERS; NERVOUS-SYSTEM; ACCIDENT; BRAIN AB Two cohorts of Chernobyl cleanup workers from Estonia (4,786 men) and Latvia (5,546 men) were followed from 1986 to 1998 to investigate cancer incidence among persons exposed to ionizing radiation from the Chernobyl accident. Each cohort was identified from various independent sources and followed using nationwide population and mortality registries. Cancers were ascertained by linkage with nationwide cancer registries. Overall, 75 incident cancers were identified in the Estonian cohort and 80 in the Latvian cohort. The combined-cohort standardized incidence ratio (SIR) for all cancers was 1.15 (95% confidence interval (CI) = 0.98-1.34) and for leukemia, 1.53 (95% CI = 0.62-3.17; n = 7). Statistically significant excess cases of thyroid (SIR = 7.06, 95% CI = 2.84-14.55; n = 7) and brain cancer (SIR = 2.14,95% CI = 1.07-3.83; n = 11) were found, mainly based on Latvian data. However, there was no evidence of a dose response for any of these sites, and the relationship to radiation exposure remains to be established. Excess of thyroid cancer cases observed may have been due to screening, the leukemia cases included 2 unconfirmed diagnoses, and the excess cases of brain tumors may have been a chance finding. There was an indication of increased risk associated with early entry to the Chernobyl area and late follow-up, though not statistically significant. Further follow-up of Chernobyl cleanup workers is warranted to clarify the possible health effects of radiation exposure. (c) 2006 Wiley-Liss, Inc. C1 Natl Inst Hlth Dev, Dept Epidemiol & Biostat, EE-11619 Tallinn, Estonia. Estonian Ctr Excellence Behav & Hlth Sci, Tartu, Estonia. STUK, Radiat & Nucl Safety Author, Helsinki, Finland. Univ Tampere, Sch Publ Hlth, FIN-33101 Tampere, Finland. Latvian Canc Registry, Riga, Latvia. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Int Epidemiol Inst, Rockville, MD USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Rahu, M (reprint author), Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Hiiu 42, EE-11619 Tallinn, Estonia. EM mati.rahu@tai.ee RI Rahu, Mati/A-9981-2008; OI Auvinen, Anssi/0000-0003-1125-4818 FU Intramural NIH HHS; NCI NIH HHS [N01-CP-85638-03] NR 51 TC 25 Z9 25 U1 0 U2 6 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 JUL 1 PY 2006 VL 119 IS 1 BP 162 EP 168 DI 10.1002/ijc.21733 PG 7 WC Oncology SC Oncology GA 041CH UT WOS:000237430200023 PM 16432838 ER PT J AU Bernstein, WB Little, RF Wilson, WH Yarchoan, R AF Bernstein, Wendy B. Little, Richard F. Wilson, Wyndham H. Yarchoan, Robert TI Acquired immunodeficiency syndrome - Related malignancies in the era of highly active antiretroviral therapy SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE acquired immunodeficiency syndrome; HAART; malignancy; Kaposi sarcoma; lymphoma; antiviral drug; cervical cancer ID SARCOMA-ASSOCIATED HERPESVIRUS; NON-HODGKINS-LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; HUMAN-PAPILLOMAVIRUS INFECTION; EPSTEIN-BARR-VIRUS; SQUAMOUS INTRAEPITHELIAL LESIONS; AIDS-RELATED LYMPHOMA; PEGYLATED LIPOSOMAL DOXORUBICIN; PROTEIN-COUPLED RECEPTOR; DOSE-ADJUSTED EPOCH AB Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, malignancies have been an important feature of this disease. Several cancers, including Kaposi sarcoma (KS), certain aggressive B-cell lymphomas, and cervical cancer, are considered AIDS-defining when they occur in patients infected with human immunodeficiency virus. Most AIDS-definine tumors are associated with one of 3 DNA viruses: KS-associated herpesvirus, Epstein-Barr virus, or human papillomavirus With the introduction of highly active antiretroviral therapy (HAART), the incidence of KS and certain lymphomas has decreased, whereas that of other tumors, such as cervical cancer, has undergone little change. Several new drugs and therapies have been developed for KS and AIDS-related lymphomas, and these treatments, plus the development of HAART, have contributed to improvements in morbidity and mortality. At the same time, the improved overall survival of patients with HAART has contributed to an increase in the number of patients living with AIDS in developed countries such as the United States. With the development of HAART and improved prevention and treatment of opportunistic infections, an increasing percentage of the deaths in AIDS patients have been from malignancies. Strategies for prevention, screening, and therapy remain important areas of research in this developing field. C1 NCI, CCR, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, CCR, Metab Branch, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, CCR, HIV & AIDS Malignancy Branch, Bldg 10,Room 10S255,10 Ctr Dr,MSC 1868, Bethesda, MD 20892 USA. EM ry1n@nih.gov FU Intramural NIH HHS NR 98 TC 22 Z9 23 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2006 VL 84 IS 1 BP 3 EP 11 DI 10.1532/IJH97.06088 PG 9 WC Hematology SC Hematology GA 068FJ UT WOS:000239357800003 PM 16867895 ER PT J AU Lever, AML Jeang, KT AF Lever, Andrew M. L. Jeang, Kuan-Teh TI Replication of human immunodeficiency virus type 1 from entry to exit SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE HIV-1; AIDS; RNAi; APOBEC3G; integration; reverse transcription; Tat; Rev ID CONSTITUTIVE TRANSPORT ELEMENT; MESSENGER-RNA EXPORT; CARBOXYL-TERMINAL DOMAIN; PROTEIN-DNA INTERACTIONS; I-HYPERSENSITIVE SITES; MURINE LEUKEMIA-VIRUS; CREB-BINDING-PROTEIN; NUCLEAR-PORE COMPLEX; HIV-1 TAT; POLYMERASE-II AB It has been 25 years since the recognition of the disease acquired immunodeficiency syndrome (AIDS) in homosexual men in the United States. Much molecular progress in understanding the replication of the human immunodeficiency virus (HIV) has been advanced. Here, we review in a nonexhaustive manner our current knowledge of the replication of HIV-1 inside human cells from entry to exit of the virus. C1 Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Lever, AML (reprint author), Univ Cambridge, Dept Med, Addenbrookes Hosp, Level 5,Box 157, Cambridge CB2 2QQ, England. EM amll1@medschl.cam.ac.uk; kjeang@mail.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Medical Research Council [G9805564] NR 118 TC 8 Z9 9 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2006 VL 84 IS 1 BP 23 EP 30 DI 10.1532/IJH97.06112 PG 8 WC Hematology SC Hematology GA 068FJ UT WOS:000239357800006 PM 16867898 ER PT J AU Yoshida, A Pommier, Y Ueda, T AF Yoshida, Akira Pommier, Yves Ueda, Takanori TI Endonuclease activation and chromosomal DNA fragmentation during apoptosis in leukemia cells SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE apoptosis; endonuclease; CAD/DFF40; AN34; endonuclease G; apurinic/apyrimidinic endonuclease 1 (Ape1); leukemia ID COLI EXONUCLEASE-III; HL-60 CELLS; RAT THYMOCYTES; REPAIR ENZYME; CA2+/MG2+-DEPENDENT ENDONUCLEASE; CHROMATIN CONDENSATION; DEOXYRIBONUCLEASE-II; EPITHELIAL-CELLS; BINDING ACTIVITY; MOLT-4 CELLS AB Apoptotic endonuclease is a key enzyme that mediates regulated DNA fragmentation and chromatin condensation in response to apoptotic signals such as the Fas ligand, ionizing radiation, and anticancer agents. An endonuclease that is activated specifically by caspase-3 has been identified in humans and mice. The human gene for this protein has been termed DFF40 (DNA fragmentation factor, 40-kd subunit) or caspase-activated nuclease (CPAN), whereas the mouse homologue has been named caspase-activated deoxyribonuclease (CAD). Although CAD/DFF40 is known as a major apoptotic nuclease, mice lacking inhibitor of CAD (ICAD) (also known as DFF45) are viable and still show DNA fragmentation, suggesting that alternative endonucleases play an important role during apoptosis. Endonuclease G has been reported to possibly be responsible for DNA fragmentation in various cells during apoptosis. Furthermore, we also have found that apurinic/apyrimidinic endonuclease 1 (Ape1) and its N-terminal-truncated form (AN34) are involved in DNA fragmentation during apoptosis in leukemia cells. In this review, we describe the features of several endonucleases that are involved in the apoptosis of human leukemia cells. Apoptotic endonuclease may vary among different leukemia cell types. C1 Univ Fukui, Fac Med Sci, Dept Internal Med 1, Matsuoka, Fukui 9101193, Japan. NCI, Mol Pharmacol Lab, Div Basic Sci, NCI, Bethesda, MD 20892 USA. RP Yoshida, A (reprint author), Univ Fukui, Fac Med Sci, Dept Internal Med 1, Matsuoka, Fukui 9101193, Japan. EM ayoshi@fmsrsa.fukui-med.ac.jp NR 70 TC 23 Z9 24 U1 1 U2 4 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2006 VL 84 IS 1 BP 31 EP 37 DI 10.1532/IJH97.06063 PG 7 WC Hematology SC Hematology GA 068FJ UT WOS:000239357800007 PM 16867899 ER PT J AU Elloumi, H Uzel, G Anderson, V Holland, SM AF Elloumi, H. Uzel, G. Anderson, V. Holland, S. M. TI Novel TTF1 mutation in a patient with hypothyroidism, chorea and mild IgA deficiency SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 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 JUL PY 2006 VL 10 SU 1 BP S3 EP S4 DI 10.1016/S1201-9712(06)80006-8 PG 2 WC Infectious Diseases SC Infectious Diseases GA 069EI UT WOS:000239428800008 ER PT J AU Kim, HS Choi, EH Roilides, E Khan, J Lyman, C Cortez, K Walsh, TJ AF Kim, H. S. Choi, E. H. Roilides, E. Khan, J. Lyman, C. Cortez, K. Walsh, T. J. TI Effect of glucocorticoids on initial gene expression of innate host defense molecules of human monocytes infected by Candida albicans SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Dongguk Univ, Ilsan, South Korea. Seoul Natl Univ, Bundang, South Korea. NCI, Bethesda, MD USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 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 JUL PY 2006 VL 10 SU 1 BP S50 EP S50 DI 10.1016/S1201-9712(06)80086-X PG 1 WC Infectious Diseases SC Infectious Diseases GA 069EI UT WOS:000239428800088 ER PT J AU Ling, J Freeman, A Collins, M Davis, J Puck, J Holland, S AF Ling, J. Freeman, A. Collins, M. Davis, J. Puck, J. Holland, S. TI Reduced bone mineral density and minimal trauma fractures in Hyper IgE syndrome SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIAID, 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 JUL PY 2006 VL 10 SU 1 BP S2 EP S3 DI 10.1016/S1201-9712(06)80004-4 PG 2 WC Infectious Diseases SC Infectious Diseases GA 069EI UT WOS:000239428800006 ER PT J AU Olivier, KN Strickland, D Stewart, W Mody, R Holland, SM AF Olivier, K. N. Strickland, D. Stewart, W. Mody, R. Holland, S. M. TI Epidemiology of nontuberculous mycobacteria in the USA: Pilot study utilizing closed healthcare systems SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. KPSC, Bethesda, MD USA. GHSP, Bethesda, MD USA. WRAMC, NIH, Bethesda, MD 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 JUL PY 2006 VL 10 SU 1 BP S8 EP S9 DI 10.1016/S1201-9712(06)80015-9 PG 2 WC Infectious Diseases SC Infectious Diseases GA 069EI UT WOS:000239428800017 ER PT J AU Sampaio, EP Shea, YR Greenberg, D Ding, L Holland, SM AF Sampaio, E. P. Shea, Y. R. Greenberg, D. Ding, L. Holland, S. M. TI Mycobacterium abscessus-induced cytokine production in human PBMC in vitro SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NIH, Dept Lab Med, 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 JUL PY 2006 VL 10 SU 1 MA 145 BP S81 EP S81 DI 10.1016/S1201-9712(06)80141-4 PG 1 WC Infectious Diseases SC Infectious Diseases GA 069EI UT WOS:000239428800143 ER PT J AU Uzel, G Heller, I Holland, SM AF Uzel, G. Heller, T. Holland, S. M. TI Infections associated with tumor necrosis factor blockade in chronic granulomatous disease SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 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 JUL PY 2006 VL 10 SU 1 BP S4 EP S4 DI 10.1016/S1201-9712(06)80007-X PG 1 WC Infectious Diseases SC Infectious Diseases GA 069EI UT WOS:000239428800009 ER PT J AU Slaughter, LA Soergel, D Rindflesch, TC AF Slaughter, Laura A. Soergel, Dagobert Rindflesch, Thomas C. TI Semantic representation of consumer questions and physician answers SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE semantic processing; public health; unified medical language system; information retrieval; natural language processing ID HEALTH INFORMATION-RETRIEVAL; TEXT AB The aim of this study was to identify the underlying semantics of health consumers' questions and physicians' answers in order to analyze the semantic patterns within these texts. We manually identified semantic relationships within question-answer pairs from Ask-the-Doctor Web sites. Identification of the semantic relationship instances within the texts was based on the relationship classes and structure of the Unified Medical Language System (UMLS) Semantic Network. We calculated the frequency of occurrence of each semantic relationship class, and conceptual graphs were generated, joining concepts together through the semantic relationships identified. We then analyzed whether representations of physician's answers exactly matched the form of the question representations. Lastly, we examined characteristics of the answer conceptual graphs. We identified 97 semantic relationship instances in the questions and 334 instances in the answers. The most frequently identified semantic relationship in both questions and answers was brings-about (causal). We found that the semantic relationship propositions identified in answers that most frequently contain a concept also expressed in the question were: brings-about, isa, co-occurs-with, diagnoses, and treats. Using extracted semantic relationships from real-life questions and answers can produce a valuable analysis of the characteristics of these texts. This can lead to clues for creating semantic-based retrieval techniques that guide users to further information. For example, we determined that both consumers and physicians often express causative relationships and these play a key role in leading to further related concepts. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Natl Hosp Norway, Radiumhosp RH, Ctr Shared Decis Making & Nursing Res, N-0027 Oslo, Norway. Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. Natl Lib Med, Bethesda, MD USA. RP Slaughter, LA (reprint author), Natl Hosp Norway, Radiumhosp RH, Ctr Shared Decis Making & Nursing Res, Forskningsveien 2B,4 Etg, N-0027 Oslo, Norway. EM laura.slaughter@rikshospitalet.no FU NLM NIH HHS [LM 07079-11] NR 35 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD JUL PY 2006 VL 75 IS 7 BP 513 EP 529 DI 10.1016/j.ijmedinf.2005.07.025 PG 17 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 052PF UT WOS:000238244900002 PM 16125448 ER PT J AU Chen, G Schloesser, R Manji, HK AF Chen, G. Schloesser, R. Manji, H. K. TI Mood stabilizers and neurogenesis SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Lab Mol Pathophysiol, Mood & Anxiety Disorders Res Program, Bethesda, MD USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S87 EP S87 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500350 ER PT J AU Cropley, V Fujita, M Bara-Jimenez, W Sangare, J Brown, A Musachio, J Hong, J Zhang, X Berman, K Herscovitch, P Pike, V Hallett, M Nathan, PJ Innis, R AF Cropley, V. Fujita, M. Bara-Jimenez, W. Sangare, J. Brown, A. Musachio, J. Hong, J. Zhang, X. Berman, K. Herscovitch, P. Pike, V. Hallett, M. Nathan, P. J. Innis, R. TI Relationship between dopamine synthesis, D-1 receptors and frontostriatal cognitive function in Parkinson's disease SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Monash Univ, Melbourne, Vic 3004, Australia. NIMH, Gene Cognit & Psychosis Program, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S127 EP S128 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500499 ER PT J AU Du, J Creson, T Wei, Y Falke, C Gray, N Szabo, S Chen, W Yuan, P Chen, G Manji, HK AF Du, J. Creson, T. Wei, Y. Falke, C. Gray, N. Szabo, S. Chen, W. Yuan, P. Chen, G. Manji, H. K. TI Modulation of AMPA glutamate receptor trafficking by antimanic agents: New avenues for drug development SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S15 EP S16 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500060 ER PT J AU Fox, M Murphy, D AF Fox, M. Murphy, D. TI Exaggerated serotonin syndrome in serotonin transporter knockout mice SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, NIH, LCS, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S174 EP S175 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501100 ER PT J AU Guiard, BP El Mansari, M Murphy, D Blier, P AF Guiard, B. P. El Mansari, M. Murphy, D. Blier, P. TI Altered response to escitalopram in heterozygous mice for the serotonin transporter SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON, Canada. NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. RI Guiard, Bruno/A-3955-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S121 EP S121 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500475 ER PT J AU Holmes, A Wellman, CL AF Holmes, A. Wellman, C. L. TI Cortico-limbic regulation of affect: The influence of genes and environmental stress SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD USA. Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. Indiana Univ, Program Neurosci, Bloomington, IN 47405 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S46 EP S47 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500189 ER PT J AU Kling, MA AF Kling, M. A. TI CNS neuroendocrinology of melancholic depression SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, Bethesda, MD USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 9 SU 1 BP S74 EP S74 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500300 ER PT J AU Lee, CT Amable, R Hayashi, T Sanchez, J Wang, E Shen, J Becker, K Freed, W AF Lee, C. T. Amable, R. Hayashi, T. Sanchez, J. Wang, E. Shen, J. Becker, K. Freed, W. TI Gene expression profiling reveals distinct cocaine-responsive genes in human fetal CNS cell types SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIDA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S165 EP S166 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501067 ER PT J AU Maeng, S Li, X Du, J Creson, T Zarate, CA Chen, G Manji, HK AF Maeng, S. Li, X. Du, J. Creson, T. Zarate, C. A., Jr. Chen, G. Manji, H. K. TI Facilitation of AMPA/NMDA throughput may underlie the antidepressant-like effects of glutamatergic agents SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Mood & Anx Disorders Res Program, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 9 SU 1 BP S211 EP S211 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501232 ER PT J AU Manji, HK AF Manji, H. K. TI Critical roles for mitochondria-ER networks in the pathophysiology and treatment of bipolar disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Lab Mol Pathophysiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S83 EP S83 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500333 ER PT J AU Mori, T Cormaci, G Hayashi, T Su, TP AF Mori, T. Cormaci, G. Hayashi, T. Su, T. -P. TI Sigma-1 receptor expression in a neurobiastoma cellular model: Effects of psychostimulants and cyclic amp-associated downstream signalings SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIDA, Cellular Pathobiol Unit, DPS, CNRB,IRP,NIH,DHHS, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S167 EP S167 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501072 ER PT J AU Post, RM Leverich, GS Altshuler, LL Frye, MS Nolen, WA Kupka, RW Suppes, T McElroy, S Keck, P Denicoff, KD Grunze, H AF Post, R. M. Leverich, G. S. Altshuler, L. L. Frye, M. S. Nolen, W. A. Kupka, R. W. Suppes, T. McElroy, S. Keck, P., Jr. Denicoff, K. D. Grunze, H. TI Switch rates of new-generation antidepressants in adjunctive treatment of bipolar depression SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, DHHS, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Groningen Hosp, Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45221 USA. Cincinnati Vet Affairs Med Ctr, Gen Clin Res Ctr, Cincinnati, OH USA. Cincinnati Vet Affairs Med Ctr, Mental Hlth Care Line, Cincinnati, OH USA. Univ Munich, Munich, Germany. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S13 EP S13 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500048 ER PT J AU Roth, BL AF Roth, B. L. TI Magic bullets vs. magic shotguns: Selectively non-selective drugs for schizophrenia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S59 EP S59 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500237 ER PT J AU Shaltiel, G Maeng, S Rogawski, M Gasior, M Chen, G Husseini, KM AF Shaltiel, G. Maeng, S. Rogawski, M. Gasior, M. Chen, G. Husseini, K. Manji TI Glur6 knockout mice concurrently display multiple behaviors related to manic symptoms SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009; Chen, Guang/A-2570-2017 OI Rogawski, Michael/0000-0002-3296-8193; NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S178 EP S179 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501115 ER PT J AU Trivedi, MH AF Trivedi, M. H. TI Issues and challenges around anxiety and depression: Co-conspirators for chronicity SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 Univ Texas, SW Med Sch, Natl Coordinat Ctr, NIMH STAR D,Mood Disorders Res Program & Clin, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S93 EP S93 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500375 ER PT J AU Tsai, SY Hayashi, T Su, TP AF Tsai, S. -Y. Hayashi, T. Su, T. -P TI Hippocampal dendritogenesis and associated anchoring of NMDA and AMPA receptors are controlled by sigma-1 receptors SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIDA, IRP, DHHS,Cell Neurobiol Res Branch, Cellular Pathobiol Unit,DPS,NIH, Bethesda, MD 20892 USA. RI Hayashi, Teruo/A-9690-2008 NR 0 TC 3 Z9 3 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S213 EP S214 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501240 ER PT J AU Weinberger, D AF Weinberger, D. TI Understanding the pathways and disorders of executive dysfunction SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S94 EP S95 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500381 ER PT J AU Wendland, J Kruse, M Murphy, D AF Wendland, J. Kruse, M. Murphy, D. TI Serotonin transporter (SERT) 1425V and other rare functional variants of SERT, DAT and SLITRK1 in obsessive-compulsive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, NIH, LCS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S194 EP S194 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495501168 ER PT J AU Zarate, CA AF Zarate, C. A., Jr. TI Dissecting the molecular pharmacology of the glutamatergic system in mood disorders: Insights from novel clinical studies SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 25th CINP Congress CY JUL 09-13, 2006 CL Chicago, IL SP CINP C1 NIMH, Lab Mol Pathophysiol Mood & Anxiety Disorders Pro, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2006 VL 9 SU 1 BP S15 EP S15 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 070BO UT WOS:000239495500058 ER PT J AU Hasler, G Gergen, PJ Ajdacic, V Gamma, A Eich, D Rossler, W Angst, J AF Hasler, G Gergen, PJ Ajdacic, V Gamma, A Eich, D Rossler, W Angst, J TI Asthma and body weight change: a 20-year prospective community study of young adults SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE asthma; depression; child development ID MASS INDEX; NUTRITION EXAMINATION; NATIONAL-HEALTH; CAUSAL RELATION; OBESITY; DEPRESSION; CHILDREN; SYMPTOMS; ZURICH; COHORT AB Objective: There is increasing evidence for an association between asthma and body weight change. The objectives of these analyses were to examine the temporal relationships of this association and to explore the role of childhood depression as an explanatory factor. Methods: Data were derived from six subsequent semistructured interviews on health habits and health conditions from a single-age community study of 591 young adults followed up between ages 20 and 40 years. Results: Cross-sectionally (over the whole study period), asthma was significantly associated with obesity (odds ratio = 3.9 [95% confidence interval 1.2, 12.2]). Multivariate longitudinal analyses revealed that asthma was associated with increased later weight gain and later obesity among women after controlling for potentially confounding variables, whereas weight gain and obesity were not associated with later asthma. A secondary analysis showed that depressive symptoms during childhood were associated with adult obesity and asthma, partially explaining the asthma-obesity comorbidity. Conclusion: This study encourages further research on mechanisms underlying the asthma-obesity comorbidity, particularly on shared psychosocial factors operating during critical periods in childhood and adolescence that may influence the development and persistence of both obesity and asthma during adulthood. C1 Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. Psychiat Univ Hosp, Zurich, Switzerland. Natl Inst Allergy & Infect Dis, Div Allergy Immunol Transplantat, Asthma Allergy Inflammat Branch, Bethesda, MD USA. RP Hasler, G (reprint author), Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, Intramural Res Program, 15K North Dr,Room 200,MSC 2670, Bethesda, MD 20892 USA. EM gregor.hasler@usz.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Ajdacic-Gross, Vladeta/0000-0002-7032-9237 NR 41 TC 25 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 2006 VL 30 IS 7 BP 1111 EP 1118 DI 10.1038/sj.ijo.0803215 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 057TN UT WOS:000238618200014 PM 16491113 ER PT J AU Bailar, JC Ballal, SG Boback, M Castleman, B Chee, HL Cherniack, M Christiani, D Cicolella, A De D'Pool, JF Egilman, D Frank, AL Garcia, MA Giannasi, F Greenberg, M Harrison, RJ Huff, J De Souza, EJ Joshi, TK Kamuzora, P Kazan-Allen, L Kern, DG Kromhout, H Kuswadji, S Ladou, J Lemen, RA Levenstein, C Luethje, B Mancini, F Meel, BL Mekonnen, Y Mendes, R Murie, D Myers, JE O'Neill, R Cisaro, E Paek, D Richter, E Robertson, H Rosskam, E Samuels, SW Soskolne, CL Stuckey, R Teitelbaum, DT Terracini, B Thebaud-Mony, A Vanhoorne, M Wang, XR Watterson, A Wedeen, R AF Bailar, John C., III Ballal, Seifeddin Gaafar Boback, Martin Castleman, Barry Chee, Heng Leng Cherniack, Martin Christiani, David Cicolella, Andre De D'Pool, Janice Fernandez Egilman, David Frank, Arthur L. Garcia S, Marco A. Giannasi, Fernanda Greenberg, Morris Harrison, Robert J. Huff, James De Souza, Eliezer Joao Joshi, Tushar Kant Kamuzora, Peter Kazan-Allen, Laurie Kern, David G. Kromhout, Hans Kuswadji, Sudjoko LaDou, Joseph Lemen, Richard A. Levenstein, Charles Luethje, Boy Mancini, Francesca Meel, Banwari Lal Mekonnen, Yalemtsehay Mendes, Rene Murie, Fiona Myers, Jonathan E. O'Neill, Rory Cisaro, Erhabor Paek, Domyung Richter, Elihu Robertson, Hugh Rosskam, Ellen Samuels, Sheldon W. Soskolne, Colin L. Stuckey, Rwth Teitelbaum, Daniel T. Terracini, Benedetto Thebaud-Mony, Annie Vanhoorne, Michel Wang, Xiaorong Watterson, Andrew Wedeen, Richard TI FIOH-sponsored newsletter misrepresents asbestos hazards in Zimbabwe SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE FIOH; WHO; ILO; journal publication; ethics; industry; influence AB The Finnish Institute of Occupational Health (FIOH) has received support from the World Health Organization (WHO) and the International Labor Office (ILO) to publish the African Newsletter on Occupational Health and Safety. The African Newsletter on Occupational Health and Safety should not be a medium for industry propaganda, or the source of misinformation among the workers of Africa. Instead, FIOH should provide the same level of scientific information in Africa that it does in Finland and other developed countries. C1 Univ Chicago, Chicago, IL 60637 USA. King Faisal Univ, Coll Med, Dammam, Saudi Arabia. UCL, Dept Epidemiol & Publ Hlth, London, England. Natl Univ Singapore, Asia Res Inst, Singapore 117548, Singapore. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Natl Inst Ind Environm & Risks, Hlth Risk Assessment Unit, Verneuil En Halatte, France. Univ Zulia, Inst Med Trabajo & Higiene Ind, Zulia, Venezuela. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. Occupat Med, San Jose, Costa Rica. Virtual Citizen Network Ban Asbestos Latin Amer, Sao Paulo, Brazil. Dept Hlth, London SE1 6TE, England. Univ Calif San Francisco, Sch Med, Int Ctr Occupat Med, San Francisco, CA 94143 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. George Washington Univ, Sch Publ Hlth, Washington, DC USA. Brazilian Asbestos Victims Assoc, Sao Paulo, Brazil. Ctr Environm & Occupat Hlth, New Delhi, India. Univ Dar Es Salaam, Inst Dev Studies, Dar Es Salaam, Tanzania. Int Ban Asbestos Secretariat, Stanmore, Middx, England. Univ Utrecht, Environm & Occupat Hlth Div, Utrecht, Netherlands. Yayasan IDKI Fdn Occupat Hlth, Tangarang, Indonesia. United States Publ Hlth Serv, Washington, DC USA. Univ Massachusetts, Lowell, MA USA. Goethe Univ Frankfurt, Inst Social Res, D-6000 Frankfurt, Germany. Wageningen Univ, Biol Farming Syst Grp, Wageningen, Netherlands. Walter Sisulu Univ Sci & Technol, Mthatha, South Africa. Univ Addis Ababa, Aklilu Lemma Inst Pathobiol, Addis Ababa, Ethiopia. Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. Bldg Workers Int, Geneva, Switzerland. Univ Cape Town, Sch Publ Hlth, Occupat & Environm Hlth Res Unit, ZA-7925 Cape Town, South Africa. Int Federat Journalists, Sheffield, S Yorkshire, England. Hazards Magazine, Sheffield, S Yorkshire, England. Univ Port Harcourt, Teaching Hosp, Port Harcourt, Nigeria. Seoul Natl Univ, Sch Publ Hlth, Seoul, South Korea. Hebrew Univ Jerusalem, Hadassah Sch Publ Hlth & Community Med, Jerusalem, Israel. Trades Union Congress, London, England. Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada. Monash Univ, Ctr Environm & Occupat Hlth, Melbourne, Vic 3004, Australia. Univ Colorado, Sch Med, Denver, CO 80202 USA. Colorado Sch Mines, Denver, CO 80202 USA. Univ Turin, Ctr Canc Prevent, Turin, Italy. Univ Paris, Sci Grp Occupat Canc, F-75252 Paris, France. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Stirling, Occupat & Environm Hlth Res Grp, Stirling FK9 4LA, Scotland. W China Univ Med Sci, Sch Publ Hlth, Chengdu, Peoples R China. Univ Ghent, B-9000 Ghent, Belgium. RP Bailar, JC (reprint author), Univ Chicago, Chicago, IL 60637 USA. RI Kromhout, Hans/A-9159-2008; Paek, Domyung/D-5747-2012 NR 16 TC 3 Z9 3 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2006 VL 12 IS 3 BP 254 EP 258 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 077QD UT WOS:000240043900010 PM 16967833 ER PT J AU Wallace, DJ Shen, DF Reed, GF Miyanaga, M Mochizuki, M Sen, HN Dahr, SS Buggage, RR Nussenblatt, RB Chan, CC AF Wallace, DJ Shen, DF Reed, GF Miyanaga, M Mochizuki, M Sen, HN Dahr, SS Buggage, RR Nussenblatt, RB Chan, CC TI Detection of the bcl-2 t(14;18) translocation and proto-oncogene expression in primary intraocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; POLYMERASE-CHAIN-REACTION; T(14-18) CHROMOSOMAL TRANSLOCATION; FOLLICULAR LYMPHOMA; CLINICAL-FEATURES; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; GENE REARRANGEMENT AB PURPOSE. Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma that initially infiltrates the retina, vitreous, or optic nerve head, with or without central nervous system involvement. This study examined the expression of the bcl-2 t(14; 18) translocation, the bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells. METHODS. Microdissection and PCR analysis were used to examine vitreous specimens in patients with PIOL for the presence of bcl-2 t(14; 18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical record review was also conducted to determine whether the bcl-2 t(14; 18) translocation correlated with prognosis. RESULTS. Forty of 72 (55%) PIOL patients expressed the bcl-2 t(14; 18) translocation at the major breakpoint region. Fifteen of 68 (22%) patients expressed the translocation at the minor cluster region. The bcl-10 gene was detected in 6 of 26 (23%) patients, whereas 4 of 4 (100%) PIOL patients expressed higher levels of bcl-6 mRNA compared with inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients revealed no significant association between bcl-2 t(14; 18) translocations and survival or relapse. However, patients with the translocation were significantly younger. CONCLUSIONS. PIOL has unique molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with other systemic lymphomas. This study lays the foundation for future studies aimed at exploring the genotypic classification of PIOL based on the quantitative molecular framework of gene expression profiling, with the goal of providing useful adjuncts to the pathologic diagnosis of this complex disease. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20895 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20895 USA. Tokyo Med & Dent Univ, Dept Ophthalmol, Tokyo, Japan. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20895 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 61 TC 13 Z9 16 U1 0 U2 0 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 JUL PY 2006 VL 47 IS 7 BP 2750 EP 2756 DI 10.1167/iovs.05-1312 PG 7 WC Ophthalmology SC Ophthalmology GA 058TX UT WOS:000238688600002 PM 16799010 ER PT J AU Haywood-Watson, RJL Ahmed, ZM Kjellstrom, S Bush, RA Takada, Y Hampton, LL Battey, JF Sieving, PA Friedman, TB AF Haywood-Watson, RJL Ahmed, ZM Kjellstrom, S Bush, RA Takada, Y Hampton, LL Battey, JF Sieving, PA Friedman, TB TI Ames waltzer deaf mice have reduced electroretinogram amplitudes and complex alternative splicing of Pcdh15 transcripts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SYNDROME TYPE 1D; USHER-SYNDROME; INNER-EAR; RETINAL DYSFUNCTION; PROTOCADHERIN GENE; ALLELIC MUTATIONS; MUTANT ALLELES; CADHERIN GENE; HEARING-LOSS; MOUSE MODEL AB PURPOSE. Mutations of PCDH15, the gene encoding protocadherin 15, cause either nonsyndromic deafness DFNB23 or Usher syndrome type 1F ( USH1F) in humans and deafness with balance problems in Ames waltzer ( av) mice. Persons with USH1 usually begin to exhibit signs of retinitis pigmentosa ( RP) in early adolescence, but av mice are reported to have functional retinas. In this study, the auditory, visual and molecular biological phenotype of Pcdh15(av-5J) and Pcdh15(av-Jfb) mice is characterized, and their usefulness as animal models of USH1 is evaluated. METHODS. Hearing thresholds of mice between 6 and 10 weeks of age were measured by auditory brain stem response ( ABR). Immunohistochemistry and histology were used to examine the effect of homozygosity of Pcdh15(av-5J) on stereocilia bundles of inner ear hair cells and on the photoreceptor cells of the retina. Scotopic and photopic Ganzfeld ERGs were recorded from homozygous Pcdh15(av-5J) and Pcdh15(av-Jfb) mice at different ages. Heterozygous littermates served as control subjects. Measurements of the width of the outer nuclear layer ( ONL) and the length of rod photoreceptor outer segment ( ROS) were made. RESULTS. Homozygous Pcdh15(av-5J) mice have profound hearing loss and disorganized stereocilia bundles of inner ear hair cells. Compared with heterozygous littermates, homozygous Pcdh(15av-5J) and Pcdh15(av Jfb) mutant mice had scotopic ERG amplitudes consistently reduced by approximately 40% at all light intensities. The b- to- a- wave ratio confirmed that the a- and b- waves were reduced proportionally in homozygous mutant mice. Histologic measurements of retinal sections revealed no significant differences in either the ONL width or the ROS length as a function of genotype. The protocadherin 15 labeling pattern with antisera PB303 in the retina of both heterozygous and homozygous Pcdh15(av-5J) mice was indistinguishable from the wild type. Wild- type Pcdh15 have many alternatively spliced isoforms. A novel isoform was found in the retina of homozygous Pcdh15(av-5J) mice, which appears to circumvent the effect of the mutant allele ( IVS14- 2A -> G), which causes skipping of exon 14, a shift in the translation reading frame and a premature stop codon in exon 15. CONCLUSIONS. Pcdh15(av-5J) and Pcdh15(av-Jfb) mice do not faithfully mimic the RP found in USH1 due to mutations of PCDH15, but have significantly attenuated ERG function in the absence of histologic change. The decline in ERG amplitude with a preserved b- to- a- wave ratio suggests a role for Pcdh15 in retinal function and/ or generation of the ERG potentials. Understanding the molecular mechanism by which av mice circumvent degeneration of the retina might offer insights into potential therapies for USH1. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. Tulane Univ, Mol & Cellular Biol Program, New Orleans, LA 70118 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov FU Intramural NIH HHS NR 63 TC 25 Z9 26 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 7 BP 3074 EP 3084 DI 10.1167/iovs.06-0108 PG 11 WC Ophthalmology SC Ophthalmology GA 058TX UT WOS:000238688600046 PM 16799054 ER PT J AU Nelson, GW O'Brien, SJ AF Nelson, GW O'Brien, SJ TI Using mutual information to measure the impact of multiple genetic factors on AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE attributable fraction; mutual information; explained variation; multifactorial disease; AIDS host genetic factors ID CASSETTE TRANSPORTER 1; EXPLAINED VARIATION; LOGISTIC-REGRESSION; PREDICTIVE ACCURACY; TANGIER-DISEASE; RESTRICTION; INFECTION AB Since the discovery of the 32-base-pair deletion in the CCR5 chemokine receptor gene (CCR5-Delta 32) and its effect oil HIV-1 infection and AIDS progression, many genetic factors affecting AIDS have been identified. Here we quantify the impact of 13 of these factors on AIDS progression using a new statistic based oil the mutual information between causal factors and disease, the explained fraction. The influence of causal factors oil disease is commonly measured by the attributable fraction statistic, but the attributable fraction is a poor measure of the extent to which a factor explains disease because it considers only whether a factor is necessary, not whether it is sufficient. The definition of the explained fraction, which is analogous to R-2 or the explained variation for regression models, extends naturally to multiple factor levels. Because the explained fraction is approximately additive, it can be used to estimate how much of epidemiological data is explained by known genetic or environmental factors, and conversely how Much is yet to be explained by unknown factors. We show that 13 genetic factors can cumulatively explain 9% of slow progression to AIDS, an effect comparable to the effect of smoking on lung cancer. C1 NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Nelson, GW (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, Bldg 560,Room 21-64, Frederick, MD 21702 USA. EM nelsong@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 24 TC 16 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL PY 2006 VL 42 IS 3 BP 347 EP 354 DI 10.1097/01.qai.0000219786.88786.d8 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 059XZ UT WOS:000238766800013 PM 16763524 ER PT J AU Katanoda, K Qiu, DM AF Katanoda, Kota Qiu, Dongmei TI International comparisons of cumulative risk of uterine cancer, from Cancer Incidence in Five Continents Vol. VIII SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 NCI, Res Ctr Canc Prevent & Screening, Stat & Canc Control Div, Bethesda, MD 20892 USA. RP Katanoda, K (reprint author), NCI, Res Ctr Canc Prevent & Screening, Stat & Canc Control Div, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0368-2811 J9 JPN J CLIN ONCOL JI Jpn. J. Clin. Oncol. PD JUL PY 2006 VL 36 IS 7 BP 474 EP 475 DI 10.1093/jjco/hyl070 PG 2 WC Oncology SC Oncology GA 075RK UT WOS:000239902700012 PM 16887841 ER PT J AU Barnes, KC Grant, A Gao, PS Baltadjieva, D Berg, T Chi, P Zhang, S Zambelli-Weiner, A Ehrlich, E Zardkoohi, O Brummet, ME Stockton, M Watkins, T Gao, L Gittens, M Wills-Karp, M Cheadle, C Beck, LA Beaty, TH Becker, KG Garcia, JGN Mathias, RA AF Barnes, Kathleen C. Grant, Audrey Gao, Peisong Baltadjieva, Daniela Berg, Tiina Chi, Peter Zhang, Shu Zambelli-Weiner, April Ehrlich, Eva Zardkoohi, Omeed Brummet, Mary E. Stockton, Maria Watkins, Tonya Gao, Li Gittens, Marquita Wills-Karp, Marsha Cheadle, Christopher Beck, Lisa A. Beaty, Terri H. Becker, Kevin G. Garcia, Joe G. N. Mathias, Rasika A. TI Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE CD14; acylotyacyl hydroxylase; association; asthma; total IgE; soluble CD14; family-based association test ID SOLUBLE CD14 LEVELS; ENDOTOXIN-NEUTRALIZING CAPACITY; GENOME-WIDE SCAN; PROMOTER POLYMORPHISM; BACTERIAL LIPOPOLYSACCHARIDES; SUSCEPTIBILITY LOCI; HUMAN-NEUTROPHILS; IGE CONCENTRATION; LEUKOCYTE ENZYME; IMMUNOGLOBULIN-E AB Background: The gene encoding acyloxyacyl hydroxylase (AOAH), an enzyme that hydrolyzes secondary fatty acyl chains of LPS, is localized on chromosome 7p14-p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has been previously reported. Objective: We hypothesized that variants in AOAH are associated with asthma and related phenotypes. Because both AOAH and soluble CD14 respond to LPS, we tested for gene-gene interaction. Methods: We investigated the association between 28 single nucleotide polymorphisms throughout the AOAH gene and asthma, concentrations of tIgE, the ratio of IL-13/IFN-gamma, and soluble CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n = 834). Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH genotype. Results: Significant effects were observed for all 4 phenotypes and AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon 13 boundary/intron 13 region) by means of single-marker and haplotype analyses, with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and log[tIgE] (P = .006). There was no difference in AOAH expression levels by AOAH genotype for any of the markers. Comparing genotypic distributions at both the AOAH marker rs2727831 and CD14(-260)C > T raises the possibility of gene-gene interaction (P = .006-.036). Conclusion: Our results indicate that polymorphisms in markers within the AOAH gene are associated with risk of asthma and-associated quantitative traits (IgE and cytokine levels) among asthmatic subjects and their families in Barbados, and there is an interactive effect on tIgE and asthma concentrations between an AOAH marker and the functional CD14(-260)C > T polymorphism. Clinical implications: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population. C1 Johns Hopkins Univ, Dept Med, Div Clin Immunol & Allergy, Baltimore, MD 21218 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. Johns Hopkins Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD USA. Johns Hopkins Univ, Johns Hopkins Sch Med, Baltimore, MD 21218 USA. Childrens Hosp, Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA. Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA. NIA, DNA Array Unit, Baltimore, MD 21224 USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Barnes, KC (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle,Rm 3A-62, Baltimore, MD 21224 USA. EM kbarnes@jhmi.edu RI Garcia, Joe/E-8862-2010; OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS; NHLBI NIH HHS [HL 67736, U01 HL 66615]; NIAID NIH HHS [AI 50024-03, R01 AI045839] NR 65 TC 26 Z9 28 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2006 VL 118 IS 1 BP 70 EP 77 DI 10.1016/j.jaci.2006.03.036 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 065UH UT WOS:000239184800008 PM 16815140 ER PT J AU Gilani, GS Betz, JM AF Gilani, G. Sarwar Betz, Joseph M. TI Role of accurate methodology in demonstrating the safety and efficacy of phytoestrogens SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 Hlth Canada, Ottawa, ON K1A 0L2, Canada. Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD USA. RP Gilani, GS (reprint author), Hlth Canada, Ottawa, ON K1A 0L2, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2006 VL 89 IS 4 BP 1120 EP 1120 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 069TH UT WOS:000239470600031 PM 16915854 ER PT J AU Jefferson, WN Padilla-Banks, E Newbold, RR AF Jefferson, Wendy N. Padilla-Banks, Elizabeth Newbold, Retha R. TI Studies of the effects of neonatal exposure to genistein on the developing female reproductive system SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR-BETA; SOY-BASED FORMULA; POLYOVULAR FOLLICLES; UDP-GLUCURONOSYLTRANSFERASE; PHYTOESTROGEN GENISTEIN; DEVELOPMENTAL EXPOSURE; DIETHYLSTILBESTROL DES; UTERINE ADENOCARCINOMA; MAMMARY TUMORIGENESIS AB Studies have shown that developmental exposure to genistein alters murine reproductive differentiation, resulting in abnormal ovarian development (multioocyte follicles) and uterine neoplasia later in life. Further, reproductive function was altered. Prolonged estrous cyclicity was observed following neonatal genistein treatment (0.5-50 mg/kg) on Days 1-5 with dose and age-related increase in severity. Fertility, determined at 2, 4, and 6 months, showed decreased numbers of genistein-treated females (0.5 or 5 mg/kg) delivering live pups and reduced numbers of pups. At 6 months, 60% of 0.5 mg/kg and 40% of 5 mg/kg groups delivered live pups compared to 100% of controls. At 2 months, half the mice treated with 25 mg/kg of genistein and none treated with 50 mg/kg delivered live pups, although half of the latter group showed signs of pregnancy with few small implantation sites. Ovarian function was disrupted in the low genistein-dosed mice with increased numbers of corpora lutea (CLs) compared to controls and increased ovulated oocytes following exogenous gonadotropins treatment. In contrast, mice treated with high genistein doses had decreased numbers of CLs; ovulation could be restored with exogenous gonadotropins. Thus, neonatal treatment with genistein at environmentally relevant doses caused adverse consequences on ovarian development and reproductive function. C1 NIEHS, NIH, Dept Hlth & Human Serv, Dev Endocrinol & Endocrine Disruptor Sect,Lab Mol, Res Triangle Pk, NC 27709 USA. RP Jefferson, WN (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Dev Endocrinol & Endocrine Disruptor Sect,Lab Mol, POB 12233, Res Triangle Pk, NC 27709 USA. EM jeffers1@niehs.nih.gov FU Intramural NIH HHS NR 74 TC 22 Z9 23 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2006 VL 89 IS 4 BP 1189 EP 1196 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 069TH UT WOS:000239470600040 PM 16918037 ER PT J AU Grieshaber, NA Sager, JB Dooley, CA Hayes, SF Hackstadt, T AF Grieshaber, Nicole A. Sager, Janet Burgess Dooley, Cheryl A. Hayes, Stanley F. Hackstadt, Ted TI Regulation of the Chlamydia trachomatis histone H1-like protein Hc2 is IspE dependent and IhtA independent SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GENOME SEQUENCE; DEVELOPMENTAL CYCLE; DNA; GENE; TRANSLATION; EXPRESSION; HOMOLOG AB The chlamydial histone-like proteins, Hc1 and Hc2, function as global regulators of chromatin structure and gene expression. Hc1 and Hc2 expression and activity are developmentally regulated. A small metabolite that disrupts Hc1 interaction with DNA also disrupts Hc2 interactions; however, the small regulatory RNA that inhibits Hc1 translation is specific to Hc1. C1 NIAID, Lab Intracellular Parasites, Host Parasite Interact Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Lab Intracellular Parasites, Host Parasite Interact Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU Intramural NIH HHS NR 20 TC 20 Z9 21 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2006 VL 188 IS 14 BP 5289 EP 5292 DI 10.1128/JB.00526-06 PG 4 WC Microbiology SC Microbiology GA 064HH UT WOS:000239079300030 PM 16816202 ER PT J AU Nason, M AF Nason, M. TI Patterns of immune response to a vaccine or virus as measured by intracellular cytokine staining in flow cytometry: Hypothesis generation and comparison of groups SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE flow cytometry; intracellular cytokine staining; long-term non-progressors; polyfunctionality AB Candidate HIV vaccines must show an immune response in order to be considered for further testing and development. What constitutes a "response," however, is still not clear. While the hunt for a protective vaccine continues, hypotheses are being formed by studying the immune responses across cohorts of people with differing responses to the infection, as well as the immune responses formed by healthy people to other viruses, ones that are generally common and well controlled. Here we examine the functional pro. le of the immune responses of a group of HIV+ long-term non-progressors as measured by intracellular cytokine staining using polychromatic flow cytometry, and compare these responses to those of a larger group of other HIV+ people. We describe some of the types of patterns in immune response that are of interest to vaccine researchers, and compare several statistical tests appropriate for this type of data. C1 NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Nason, M (reprint author), NIAID, Biostat Res Branch, NIH, 6700B Rockledge Dr MSC 7609, Bethesda, MD 20892 USA. EM mnason@niaid.nih.gov NR 8 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JUL-AUG PY 2006 VL 16 IS 4 BP 483 EP 498 DI 10.1080/10543400600719426 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 067BR UT WOS:000239276100008 PM 16892909 ER PT J AU Rebois, RV Robitaille, M Gales, C Dupre, DJ Baragli, A Trieu, P Ethier, N Bouvier, M Hebert, TE AF Rebois, RV Robitaille, M Gales, C Dupre, DJ Baragli, A Trieu, P Ethier, N Bouvier, M Hebert, TE TI Heterotrimeric G proteins form stable complexes with adenylyl cyclase and Kir3.1 channels in living cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE adenylyl cyclase; beta(2)-adrenergic receptor; BiFC; BRET; G-protein-coupled inwardly rectifying K+ channels; heterotrimeric G proteins ID RESONANCE ENERGY-TRANSFER; BIMOLECULAR FLUORESCENCE COMPLEMENTATION; RECTIFYING POTASSIUM CHANNELS; BETA-ADRENERGIC-RECEPTORS; GTP REGULATORY UNIT; COUPLED RECEPTORS; SIGNALING COMPLEX; CATALYTIC UNIT; GAMMA SUBUNIT; CA2+ CHANNEL AB Bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation experiments revealed that heterotrimeric G proteins and their effectors were found in stable complexes that persisted during signal transduction. Adenylyl cyclase, Kir3.1 channel subunits and several G-protein subunits (G alpha(s), G alpha(i), G beta(1) and G gamma(2)) were tagged with luciferase (RLuc) or GFP, or the complementary fragments of YFP (specifically G beta(1)-YFP1-158 and G gamma(2)-YFP159-238, which heterodimerize to produce fluorescent YFP-G beta(1)gamma(2)). BRET was observed between adenylyl-cyclase-RLuc or Kir3.1-RLuc and GFP-G gamma(2), GFP-G beta(1) or YFP-G beta(1 gamma 2). G alpha subunits were also stably associated with both effectors regardless of whether or not signal transduction was initiated by a receptor agonist. Although BRET between effectors and G beta gamma was increased by receptor stimulation, our data indicate that these changes are likely to be conformational in nature. Furthermore, receptor-sensitive G-protein-effector complexes could be detected before being transported to the plasma membrane, providing the first direct evidence for an intracellular site of assembly. C1 Natl Inst Deafness & Communicat Disorders, Rockville, MD 20850 USA. Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada. RP Rebois, RV (reprint author), Natl Inst Deafness & Communicat Disorders, Rockville, MD 20850 USA. EM reboisv@nidcd.nih.gov; terence.hebert@mcgill.ca RI Dupre, Denis/F-3044-2014; Bouvier, Michel/H-2758-2014 OI Bouvier, Michel/0000-0003-1128-0100 FU Intramural NIH HHS NR 50 TC 94 Z9 97 U1 0 U2 6 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 JUL 1 PY 2006 VL 119 IS 13 BP 2807 EP 2818 DI 10.1242/jcs.03021 PG 12 WC Cell Biology SC Cell Biology GA 054YD UT WOS:000238413600018 PM 16787947 ER PT J AU Litvin, O Tiunova, A Connell-Alberts, Y Panchin, Y Baranova, A AF Litvin, Oxana Tiunova, Anya Connell-Alberts, Yvette Panchin, Yuri Baranova, Ancha TI What is hidden in the pannexin treasure trove: the sneak peek and the guesswork SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Review DE gap junction; hemichannel; pannexin; synchronous activity; calcium waves; hippocampus; glioma; ATP release ID GAP-JUNCTION PROTEINS; BERGMANN GLIAL-CELLS; MALIGNANT GLIOMA-CELLS; RAT CEREBELLAR SLICES; RECORDED IN-VIVO; OLFACTORY-BULB; CALCIUM WAVES; GABAERGIC INTERNEURONS; GAMMA-OSCILLATIONS; GENE-EXPRESSION AB Connexins had been considered to be the only class of the vertebrate proteins capable of gap junction formation; however, new candidates for this function with no homology to connexins, termed pannexins were discovered. So far three pannexins were described in rodent and human genomes: Panx1, Panx2 and Panx3. Expressions of pannexins can be detected in numerous brain structures, and now found both in neuronal and glial cells. Hypothetical roles of pannexins in the nervous system include participating in sensory processing, hippocampal. plasticity, synchronization between hippocampus and cortex, and propagation of the calcium waves supported by glial cells, which help maintain and modulate neuronal metabolism. Pannexin also may participate in pathological reactions of the neural cells, including their damage after ischemia and subsequent cell death. Recent study revealed non-gap junction function of Panx1 hemichannels in erythrocytes, where they serve as the conduits for the ATP release in response to the osmotic stress. High-throughput studies produced some evidences of the pannexin involvement in the process of tumorigenesis. According to brain cancer gene expression database REMBRANDT, PANX2 expression levels can predict post diagnosis survival for patients with glial tumors. Further investigations are needed to verify or reject hypotheses listed. C1 George Mason Univ, Mol & Microbiol Dept, Fairfax, VA 22030 USA. Stowers Inst Med Res, Kansas City, MO USA. Russian Acad Med Sci, PK Anokhin Inst Normal Physiol, Moscow, Russia. Russian Acad Sci, Inst Informat Transmiss Problems, Moscow 101447, Russia. Moscow MV Lomonosov State Univ, AN Belozersky Inst, Moscow, Russia. Russian Acad Med Sci, Russian Ctr Med Genet, Moscow, Russia. NCI, MCGP, Frederick, MD 21701 USA. RP Baranova, A (reprint author), George Mason Univ, Mol & Microbiol Dept, David King Hall,MSN 3E1, Fairfax, VA 22030 USA. EM abaranov@gmu.edu RI Baranova, Ancha/B-4608-2012; OI Baranova, Ancha/0000-0001-6810-5982; Panchin, Yuri/0000-0002-8006-2839 NR 125 TC 38 Z9 41 U1 0 U2 1 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JUL-SEP PY 2006 VL 10 IS 3 BP 613 EP 634 DI 10.2755/jcmm010.003.04 PG 22 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 096RI UT WOS:000241394100006 PM 16989724 ER PT J AU Zheng, XX Morrison, AR Chung, AS Moss, J Bortelll, R AF Zheng, XX Morrison, AR Chung, AS Moss, J Bortelll, R TI Substrate specificity of soluble and membrane-associated ADP-ribosyltransferase ART2.1 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ADP-ribosyltransferase; NAD; post-translational modification; T-lymphocytes; serum transferrin ID CELL-SURFACE; T-CELLS; NAD GLYCOHYDROLASE; BACTERIAL TOXINS; SKELETAL-MUSCLE; RIBOSYLATION; MOUSE; PROTEIN; RAT; ACTIVATION AB ADP-ribosyltransferases (ARTs) are a family of enzymes that catalyze the covalent transfer of an ADP-ribose moiety, derived from NAD, to an amino acid of an acceptor protein, thereby altering its function. To date, little information is available on the protein target specificity of different ART family members. ART2 is a T-cell-specific transferase, attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor, and also found in serum. Here we investigated the role of ART2 localization in serum or on the cell Surface, or solubilized with detergents or enzymes, on its target protein specificity. We found that detergent solubilization of cell membranes, or release of ART2 by phosphoinositide-specific phospholipase C treatment, altered the ability of ART2 to ADP-ribosylate high or low molecular weight histone proteins. Similarly, soluble recombinant ART2 (lacking the GPI anchor) showed a different histone specificity than did cell-bound ART2. When soluble ART2 was incubated with serum proteins in the presence of [P-32]-labeled NAD, several serum proteins were ADP-ribosylated in a thiol-specific manner. Mass spectrometry of labeled proteins identified albumin and transferrin as ADP-ribosylated proteins in serum. Collectively, these studies reveal that the membrane or solution environment of ART2 plays a pivotal role in determining its substrate specificity. C1 Univ Massachusetts, Sch Med, Dept Med, Diabet Div, Worcester, MA 01605 USA. Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Bortelll, R (reprint author), Univ Massachusetts, Sch Med, Dept Med, Diabet Div, 373 Plantat St, Worcester, MA 01605 USA. EM rita.bortell@umassmed.edu FU NIDDK NIH HHS [DK32520] NR 33 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2006 VL 98 IS 4 BP 851 EP 860 DI 10.1002/jcb.20722 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 056KJ UT WOS:000238521400014 PM 16453289 ER PT J AU Philp, D Scheremeta, B Sibliss, K Zhou, M Fine, EL Nguyen, M Wahl, L Hoffman, MP Kleinman, HK AF Philp, D Scheremeta, B Sibliss, K Zhou, M Fine, EL Nguyen, M Wahl, L Hoffman, MP Kleinman, HK TI Thymosin beta(4) promotes matrix metalloproteinase expression during wound repair SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; MIGRATION; FLUID; MICE; KERATINOCYTES; ACTIVATION; INHIBITOR; THYMOSINS; ADHESION; DISEASE AB Immobilized patients, diabetics, and the elderly suffer from impaired wound healing. The 43-amino acid angiogenic peptide thymosin beta(4) (T beta(4)) has previously been found to accelerate dermal wound repair in rats, aged mice, and db/db diabetic mice. It also promotes corneal repair in both normal rats and mice. Because proteinases are important in wound repair, we hypothesized that T beta(4) may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Analysis by RT-PCR of whole excised mouse dermal wounds on days 1, 2, and 3 after wounding showed that T beta(4) increased several metalloproteinases, including MMP-2 and -9 expression by several-fold over control on day 2 after wounding. We further analyzed the metalloproteinases secreted in response to exogenous T beta(4) by cells normally present in the wound. Western blot analysis of cultured keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of T beta(4) showed increases in the levels of MMP-1, -2, and -9 in a cell-specific manner. T beta(4) also enhanced the secretion of MMP-1 and MMP-9 by activated monocytes. The central actin-binding domain, amino acids 17-23, had all of the activity for metalloproteinase induction. We conclude that part of the wound healing activity of T beta(4) resides in its abilityto increase proteinase activity via its central actin-binding domain. Thus, T beta(4) may play a pivotal role in extracellular matrix remodeling during wound repair. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Matrix Morphogenesis Unit, NIH, Bethesda, MD USA. RP Kleinman, HK (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, 30-433,30 Convent Dr,MSC-4370, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov NR 32 TC 37 Z9 40 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2006 VL 208 IS 1 BP 195 EP 200 DI 10.1002/jcp.20650 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 050RX UT WOS:000238106700021 PM 16607611 ER PT J AU Parsons, JK Carter, HB Partin, AW Windham, BG Metter, EJ Ferrucci, L Landis, P Platz, EA AF Parsons, J. Kellogg Carter, H. Ballentine Partin, Alan W. Windham, B. Gwen Metter, E. Jeffrey Ferrucci, Luigi Landis, Patricia Platz, Elizabeth A. TI Metabolic factors associated with benign prostatic hyperplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NUTRITION EXAMINATION SURVEY; ACUTE URINARY RETENTION; 3RD NATIONAL-HEALTH; FREE TESTOSTERONE; GROWTH-FACTORS; RISK-FACTORS; OBSTRUCTIVE UROPATHY; BINDING-PROTEINS; TRACT SYMPTOMS; AMERICAN MEN AB Context: Benign prostatic hyperplasia poses a significant public health problem, but its etiology remains unclear. Obesity and associated abnormalities in glucose homeostasis may play a role in benign prostatic hyperplasia development by influencing prostate growth. Objective: The objective of this study was to determine whether obesity, fasting plasma glucose concentration, and diabetes are associated with radiologically determined prostate enlargement, an objective measure of benign prostatic hyperplasia. Design: This study was a cross-sectional analysis with robust variance estimates to account for multiple measures over time in the same individuals. Setting: This prospective cohort study was composed of community volunteers. Patients: Patients studied were 422 adult men enrolled in The Baltimore Longitudinal Study of Aging. Main Outcome Measurements: Total prostate volume as determined by pelvic magnetic resonance imaging was measured. Results: Among 422 participants, 91 (21.6%) had prostate enlargement (defined as total prostate volume >= 40 cc) at first visit. Compared with men of normal weight [body mass index (BMI) < 25 kg/m(2)], the age-adjusted odds ratio (OR) for prostate enlargement for overweight men (BMI, 25-29.9 kg/m(2)) was 1.41 (95% CI, 0.84-2.37), for obese men (BMI, 30-34 kg/m(2)) was 1.27 (95% CI, 0.68-2.39), and for severely obese men (BMI >= 35 kg/m(2)) was 3.52 (95% CI, 1.45-8.56) (P = 0.01). Men with elevated fasting glucose (> 110 mg/dl) were more likely to have an enlarged prostate than men with normal fasting glucose (> 110 mg/dl) (OR, 2.98; 95% CI, 1.70-5.23), as were men with a diagnosis of diabetes (OR, 2.25; 95% CI, 1.23-4.11). Conclusions: Obesity, elevated fasting plasma glucose, and diabetes are risk factors for benign prostatic hyperplasia. C1 James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Baltimore, MD 21287 USA. NIA, Clin Res Branch, Baltimore, MD 21225 USA. Harbor Hosp, Baltimore, MD 21225 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Parsons, JK (reprint author), Univ Calif San Diego, Div Urol, 200 W Arbor Dr, Baltimore, MD 21287 USA. EM k0parsons@ucsd.edu FU Intramural NIH HHS [Z01 AG000015-49] NR 65 TC 163 Z9 204 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 JUL PY 2006 VL 91 IS 7 BP 2562 EP 2568 DI 10.1210/jc.2005-2799 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 060ZI UT WOS:000238840600018 PM 16608892 ER PT J AU Weil, RJ Vortmeyer, AO Nieman, LK DeVroom, HL Wanebo, J Oldfield, EH AF Weil, Robert J. Vortmeyer, Alexander O. Nieman, Lynnette K. DeVroom, Hetty L. Wanebo, John Oldfield, Edward H. TI Surgical remission of pituitary adenomas confined to the neurohypophysis in Cushing's disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TPIT GENE-MUTATIONS; INTERMEDIATE LOBE; TRANSSPHENOIDAL SURGERY; DIAGNOSTIC-TESTS; HUMAN ANTERIOR; ADOLESCENCE; MORTALITY; WEIGHT; MICROSURGERY; MICROADENOMA AB Context: Partial or total removal of the pituitary cures 60-80% of patients with Cushing's disease (CD) in whom an adenoma cannot be identified at surgery. Many patients who fail complete or partial hypophysectomy are cured by sellar and parasellar irradiation. Design/Patients: As part of a series of prospective studies of CD, we identified 12 patients (34.5 +/- 19.9 yr; 11 females; four children) with tumors located completely within the neurohypophysis among 730 patients undergoing surgery for CD. Setting: The study was conducted at a tertiary referral center at a clinical research hospital. Results: All 12 patients had clinical and biochemically defined CD. Tumor was visible at surgery in 11 patients; all 12 tumors were positive for ACTH by immunohistochemistry. Two tumors were excised at repeat surgery because of persistent hypercortisolism within 14 d of negative exploration of the adenohypophysis. There were no long-term complications. At follow-up of 71.9 +/- 34.2 months patients have had significant improvement in weight and body mass indices, with restoration of normal menses in all women. In the four pediatric patients, height, weight, and body mass indices have been restored toward normal by surgical remission of CD. Hypopituitarism or long-term neurohypophysial dysfunction has not occurred. Conclusion: We report a new subset of patients with CD, ACTH-secreting adenomas that arise wholly within the posterior lobe of the pituitary gland. In cases of CD in which an adenoma is not identified in the adenohypophysis and in patients with persistent hypercortisolism after complete or partial excision of the anterior lobe, tumor within the neurohypophysis should be considered; selective adenomectomy of a neurohypophyseal, ACTH-secreting tumor can produce long-term remission. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Child Hlth & Dev, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, MSC 1414,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oldfiele@ninds.nih.gov OI Wanebo, John/0000-0003-1833-2938 NR 45 TC 14 Z9 14 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 JUL PY 2006 VL 91 IS 7 BP 2656 EP 2664 DI 10.1210/jc.2006-0277 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 060ZI UT WOS:000238840600033 PM 16636117 ER PT J AU Saad, AG Kumar, S Ron, E Lubin, JH Stanek, J Bove, KE Nikiforov, YE AF Saad, Ali G. Kumar, Seena Ron, Elaine Lubin, Jay H. Stanek, Jerzy Bove, Kevin E. Nikiforov, Yuri E. TI Proliferative activity of human thyroid cells in various age groups and its correlation with the risk of thyroid cancer after radiation exposure SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ATOMIC-BOMB SURVIVORS; CHERNOBYL ACCIDENT; HUMAN FETUSES; TUMORS; CHILDHOOD; BYELARUS; IRRADIATION; CHILDREN; MIB-1 AB Context: The thyroid gland is vulnerable to the carcinogenic effects of ionizing radiation, and there is a well-documented inverse correlation between thyroid cancer and age at exposure, particularly for ages less than 20 yr. One of the factors responsible for this phenomenon may be more rapid cell proliferation in children. Objective: The objective of this study was to determine the proliferative rate of normal human thyroid cells in different age groups. Design: We used immunohistochemical analysis to determine the Ki-67 proliferative index in 117 thyroid glands obtained at autopsy, including 25 fetal thyroids (11-40 wk gestation), 55 childhood thyroids (0-19 yr), and 37 adult thyroids (20-60 yr). Results: The rate of Ki-67 labeling in the three groups was 7.4 +/- 6.10, 0.23 +/- 0.15, and 0.08 +/- 0.04% respectively, demonstrating an overall trend for diminishing proliferative activity of thyroid cells with increasing age. However, a lack of correlation was noted between the slopes of cancer risk calculated from previous studies of irradiated populations and proliferative rate in the pediatric age intervals of 0-4 and 5-9 yr, suggesting that other factors are likely to be responsible for the particularly high sensitivity to radiation-induced thyroid cancer among the youngest children. Conclusions: Our findings of a general decrease in proliferative activity of thyroid cells with age may explain, at least in part, the higher risks of radiation-related thyroid cancer in children compared with adults. However, the variation in the rate of cell proliferation is unlikely to be responsible entirely for this phenomenon and other factors may also be involved. C1 Univ Cincinnati, Dept Pathol, Cincinnati, OH 45267 USA. Univ Cincinnati, Lab Med, Cincinnati, OH 45267 USA. NCI, Bethesda, MD 20892 USA. Cincinnati Childrens Hosp, Med Ctr, Div Pathol & Lab Med, Cincinnati, OH USA. RP Nikiforov, YE (reprint author), Univ Cincinnati, Dept Pathol, 231 Albert Sabin Way,POB 670529, Cincinnati, OH 45267 USA. EM Yuri.Nikiforov@uc.edu FU Intramural NIH HHS; NCI NIH HHS [R01 CA88041] NR 32 TC 38 Z9 43 U1 0 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 JUL PY 2006 VL 91 IS 7 BP 2672 EP 2677 DI 10.1210/jc.2006-0417 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 060ZI UT WOS:000238840600035 PM 16670159 ER PT J AU Berger, VW AF Berger, Vance W. TI Response to Klassen et al: Missing data should be more heartily penalized SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter ID CONTROLLED-TRIALS; CLINICAL-TRIALS; QUALITY; BIAS C1 Univ Maryland Baltimore Cty, Biometry Res Grp, Bethesda, MD 20892 USA. Natl Canc Inst, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 2006 VL 59 IS 7 BP 759 EP 760 DI 10.1016/j.jclinepi.2006.01.001 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 055CM UT WOS:000238427600015 PM 16765281 ER PT J AU McKenzie, FE AF McKenzie, FE TI Case mortality in polymicrobial bloodstream infections SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter ID ENTEROCOCCAL BACTEREMIA; RISK-FACTORS; EXPERIENCE; SEPSIS; MODEL C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. EM em225k@nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 23 TC 21 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 2006 VL 59 IS 7 BP 760 EP 761 DI 10.1016/j.jclinepi.2005.12.009 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 055CM UT WOS:000238427600016 PM 16765282 ER PT J AU Chiang, ET Persaud-Sawin, DA Kulkarni, S Garcia, JGN Imani, F AF Chiang, Eddie T. Persaud-Sawin, Dixie-Ann Kulkarni, Sandhya Garcia, Joe G. N. Imani, Farhad TI Bluetongue virus and double-stranded RNA increase human vascular permeability: Role of p38 MAPK SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE hemorrhagic fever; vascular permeability; double-stranded RNA (dsRNA); bluetongue virus; MAP kinase ID NECROSIS-FACTOR-ALPHA; MICROVASCULAR ENDOTHELIAL-CELLS; ACTIVATED PROTEIN-KINASES; HUMAN EPITHELIAL-CELLS; TNF-ALPHA; GENE-EXPRESSION; BARRIER DYSFUNCTION; SIGNALING PATHWAYS; IN-VITRO; INFLAMMATORY CYTOKINE AB Endothelial cell (EC) involvement in viral hemorrhagic fevers has been clearly established. However, virally activated mechanisms leading to endothelial activation and dysfunction are not well understood. Several different potential mechanisms such as direct viral infection, alterations in procoagulant/anticoagulant balance, and increased cytokine production have been suggested. We utilized a model of EC barrier dysfunction and vascular endothelial leakage to explore the effect of bluetongue virus (BTV), a hemorrhagic fever virus of ruminants, on human lung endothelial cell barrier properties. Infection of human lung EC with BTV induced a significant and dose-dependent decrease in trans-endothelial electrical resistance (TER). Furthermore, decreases in TER occurred in conjunction with cytoskeletal rearrangement, suggesting a direct mechanism for viral infection-mediated endothelial barrier disruption. Interestingly, double-stranded RNA (dsRNA) mimicked the effects of BTV on endothelial barrier properties. Both BTV- and dsRNA-induced endothelial barrier dysfunction was blocked by treatment with a pharmacological inhibitor of p38 MAPK. The induction of vascular permeability by dsRNA treatment or BTV infection was concomitent with induction of inflammatory cytokines. Taken together, our data suggest that the presence of dsRNA during viral infections and subsequent activation of p38 MAPK is a potential molecular pathway for viral induction of hemorrhagic fevers. Collectively, our data suggest that inhibition of p38 MAPK may be a possible therapeutic approach to alter viral-induced acute hemorrhagic diseases. C1 NIEHS, NIH, Lab Resp Biol, Durham, NC 27709 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Imani, F (reprint author), NIEHS, NIH, Lab Resp Biol, MD 2-01,111 Alexander Dr,RTP, Durham, NC 27709 USA. EM imani@niehs.nih.gov RI Garcia, Joe/E-8862-2010 NR 74 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 2006 VL 26 IS 4 BP 406 EP 416 DI 10.1007/s10875-006-9024-4 PG 11 WC Immunology SC Immunology GA 063MG UT WOS:000239021800013 PM 16786433 ER PT J AU Xu, XL Kobayashi, S Qiao, WH Li, CL Xiao, CY Radaeva, S Stiles, B Wang, RH Ohara, N Yoshino, T LeRoith, D Torbenson, MS Gores, GJ Wu, H Gao, B Deng, CX AF Xu, Xiaoling Kobayashi, Shogo Qiao, Wenhui Li, Cuiling Xiao, Cuiying Radaeva, Svetlana Stiles, Bangyan Wang, Rui-Hong Ohara, Nobuya Yoshino, Tadashi LeRoith, Derek Torbenson, Michael S. Gores, Gregory J. Wu, Hong Gao, Bin Deng, Chu-Xia TI Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CONDITIONAL KNOCKOUT MICE; TUMOR-SUPPRESSOR; CYCLIN D1; HEPATOCELLULAR-CARCINOMA; CHOLANGIOCARCINOMA CELLS; NEGATIVE REGULATION; BETA-CATENIN; EXPRESSION; GENE; DELETION AB Cholangiocellular carcinoma (CC), the second most common primary liver cancer, is associated with a poor prognosis. It has been shown that CCs harbor alterations of a number of tumor-suppressor genes and oncogenes, yet key regulators for tumorigenesis remain unknown. Here we have generated a mouse model that develops CC with high penetrance using fiver-specific targeted disruption of tumor suppressors SMAD4 and PTEN. In the absence of SMAD4 and PTEN, hyperplastic foci emerge exclusively from bile ducts of mutant mice at 2 months of age and continue to grow, leading to tumor formation in all animals at 4-7 months of age. We show that CC formation follows a multistep progression of histopathological changes that are associated with significant alterations, including increased levels of phosphorylated AKT, FOXO1, GSK-3 beta, mTOR, and ERK and increased nuclear levels of cyclin D1. We further demonstrate that SMAD4 and PTEN regulate each other through a novel feedback mechanism to maintain an expression balance and synergistically repress CC formation. Finally, our analysis of human CC detected PTEN inactivation in a majority of p-AKT-positive CCs, while about half also lost SMAD4 expression. These findings elucidate the relationship between SMAD4 and PTEN and extend our understanding of CC formation. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, Rochester, MN USA. NIAAA, Sect Liver Biol, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmceol, Los Angeles, CA USA. Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol, Okayama, Japan. NIDDK, NIH, Diabet Branch, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Sol Goldman Canc Res Ctr, Dept Pathol, Baltimore, MD USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10 9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS; NIDDK NIH HHS [R21 DK075928] NR 49 TC 94 Z9 99 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2006 VL 116 IS 7 BP 1843 EP 1852 DI 10.1172/JCI27282 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 062DN UT WOS:000238924900018 PM 16767220 ER PT J AU Pesce, J Kaviratne, M Ramalingam, TR Thompson, RW Urban, JF Cheever, AW Young, DA Collins, M Grusby, MJ Wynn, TA AF Pesce, John Kaviratne, Mallika Ramalingam, Thirumalai R. Thompson, Robert W. Urban, Joseph F., Jr. Cheever, Allen W. Young, Deborah A. Collins, Mary Grusby, Michael J. Wynn, Thomas A. TI The IL-21 receptor augments Th2 effector function and alternative macrophage activation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SCHISTOSOMA-MANSONI; ADAPTIVE IMMUNITY; B-CELLS; NIPPOSTRONGYLUS-BRASILIENSIS; GRANULOMATOUS PATHOLOGY; ANTITUMOR RESPONSES; HEPATIC-FIBROSIS; INTERFERON-GAMMA; TISSUE FIBROSIS; IFN-GAMMA AB The IL-21 receptor (IL-21R) shows significant homology with the IL-4R, and CD4(+)Th2 cells are an important source of IL-21. Here we examined whether the IL-21R regulates the development of Th2 responses in vivo. To do this, we infected IL-21R(-/-) mice with the Th2-inducing pathogens Schistosoma mansoni and Nippostrongylus brasiliensis and examined the influence of IL-21R deficiency on the development of Th2-dependent pathology. We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. manson infected IL-21R(-/-) mice and in IL-21R(+/+) mice treated with soluble IL-21R-Fc (sIL-21R-Fc). The impaired granulomatous response was also associated with a marked reduction in Th2 cytokine expression and function, as evidenced by the attenuated IL-4, IL-13, AMCase, Ym1, and FIZZ1 (also referred to as RELM alpha) responses in the tissues. A similarly impaired Th2 response was observed following N. brasiliensis infection. In vitro, IL-21 significantly augmented IL-4R alpha and IL-13R alpha 1 expression in macrophages, resulting in increased FIZZ1 mRNA and arginase-1 activity following stimulation with IL-4 and IL-13. As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation. Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases. C1 NIAID, Immunopathol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. USDA ARS, Nutrient Requirements & Funct Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. Biomed Res Inst, Rockville, MD 20852 USA. Wyeth Res, Cambridge, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Wynn, TA (reprint author), NIAID, Immunopathol Sect, Parasit Dis Lab, NIH, Bldg 50,Room 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; OI Urban, Joseph/0000-0002-1590-8869 FU Intramural NIH HHS NR 59 TC 187 Z9 204 U1 3 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2006 VL 116 IS 7 BP 2044 EP 2055 DI 10.1172/JCI27727 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 062DN UT WOS:000238924900037 PM 16778988 ER PT J AU Francesconi, A Kasai, M Petraitiene, R Petraitis, V Kelaher, AM Schaufele, R Hope, WW Shea, YR Bacher, J Walsh, TJ AF Francesconi, Andrea Kasai, Miki Petraitiene, Ruta Petraitis, Vidmantas Kelaher, Amy M. Schaufele, Robert Hope, William W. Shea, Yvonne R. Bacher, John Walsh, Thomas J. TI Characterization and comparison of galactomannan enzyme immunoassay and quantitative real-time PCR assay for detection of Aspergillus fumigatus in bronchoalveolar lavage fluid from experimental invasive pulmonary aspergillosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PERSISTENTLY NEUTROPENIC RABBITS; RECEIVING PIPERACILLIN-TAZOBACTAM; ALLOGENEIC BMT RECIPIENTS; FUNGAL-INFECTIONS; COMPUTERIZED-TOMOGRAPHY; PLASMA PHARMACOKINETICS; ANTIFUNGAL THERAPY; ANTIGEN-DETECTION; EARLY-DIAGNOSIS; EFFICACY AB Bronchoalveolar lavage (BAL) is widely used for evaluation of patients with suspected invasive pulmonary aspergillosis (IPA). However, the diagnostic yield of BAL for detection of IPA by culture and direct examination is limited. Earlier diagnosis may be facilitated by assays that can detect Aspergillus galactomannan antigen or DNA in BAL fluid. We therefore characterized and compared the diagnostic yields of a galactomannan enzyme immunoassay (GM EIA), quantitative real-time PCR (qPCR), and quantitative cultures in experiments using BAIL fluid from neutropenic rabbits with experimentally induced IPA defined as microbiologically and histologically evident invasion. The qPCR assay targeted the rRNA gene complex of Aspergillus fumigatus. The GM EIA and qPCR assay were characterized by receiver operator curve analysis. With an optimal cutoff of 0.75. the GM EIA had a sensitivity, and specificity of 100% in untreated controls. A decline in sensitivity (92%) was observed when antifungal therapy (AFT) was administered. The optimal cutoff for qPCR was a crossover of 36 cycles, with sensitivity and specificity of 80% and 100%, respectively. The sensitivity of qPCR also decreased with AFT to 50%. Quantitative culture of BAL had a sensitivity of 46% and a specificity of 100%. The sensitivity of quantitative culture decreased with AFT to 16%. The GM EIA and qPCR assay had greater sensitivity than culture in detection of A. fumigatus in BAL fluid in experimentally induced IPA (P +/- 0.04). Use of the GM EIA and qPCR assay in conjunction with culture-based diagnostic methods applied to BAL fluid could facilitate accurate and diagnosis and more-timely initiation of specific therapy. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 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 walshtj@mail.nih.gov OI Hope, William/0000-0001-6187-878X FU Intramural NIH HHS NR 43 TC 55 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2006 VL 44 IS 7 BP 2475 EP 2480 DI 10.1128/JCM.02693-05 PG 6 WC Microbiology SC Microbiology GA 065JY UT WOS:000239157400025 PM 16825367 ER PT J AU Halvas, EK Aldrovandi, GM Balfe, P Beck, IA Boltz, VF Coffin, JM Frenkel, LM Hazelwood, JD Johnson, VA Kearney, M Kovacs, A Kuritzkes, DR Metzner, KJ Nissley, DV Nowicki, M Palmer, S Ziermann, R Zhao, RY Jennings, CL Bremer, J Brambilla, D Mellors, JW AF Halvas, Elias K. Aldrovandi, Grace M. Balfe, Peter Beck, Ingrid A. Boltz, Valerie F. Coffin, John M. Frenkel, Lisa M. Hazelwood, J. Darren Johnson, Victoria A. Kearney, Mary Kovacs, Andrea Kuritzkes, Daniel R. Metzner, Karin J. Nissley, Dwight V. Nowicki, Marek Palmer, Sarah Ziermann, Rainer Zhao, Richard Y. Jennings, Cheryl L. Bremer, James Brambilla, Don Mellors, John W. TI Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; IN-VIVO; MUTATIONS; THERAPY; POPULATIONS; INTERRUPTION; INHIBITORS; GENOTYPE; MULTIPLE; PROTEASE AB We determined the abilities of 10 technologies to detect and quantify a common drug-resistant mutant of human immunodeficiency virus type 1 (lysine to asparagine at codon 103 of the reverse transcriptase) using a blinded test panel containing mutant-wild-type mixtures ranging from 0.01% to 100% mutant. Two technologies, allele-specific reverse transcriptase PCR and a Ty1HRT yeast system, could quantify the mutant down to 0.1 to 0.4%. These technologies should help define the impact of low-frequency drug-resistant mutants on response to antiretroviral therapy. C1 Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA. Childrens Hosp Los Angeles, Keck Sch Med, Los Angeles, CA 90027 USA. Columbia Univ, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Univ So Calif, Los Angeles, CA USA. Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Univ Erlangen Nurnberg, Erlangen, Germany. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. Bayer Healthcare Diagnost, Berkeley, CA USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Rush Med Coll, Chicago, IL 60612 USA. New England Res Inst, Watertown, MA 02172 USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Dept Med, Div Infect Dis, S818 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM Mellors@msx.dept-med.pitt.edu RI Metzner, Karin/G-5319-2011 OI Metzner, Karin/0000-0003-4862-1503 FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NIAID NIH HHS [AI-60354, N01-AI-85354, N01AI85354, P30 AI027767, P30 AI060354, P30AI27767, U01 AI038858, U01AI38858, UM1 AI106716]; NICHD NIH HHS [HD 40777, R01 HD040777] NR 20 TC 84 Z9 88 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2006 VL 44 IS 7 BP 2612 EP 2614 DI 10.1128/JCM.00449-06 PG 3 WC Microbiology SC Microbiology GA 065JY UT WOS:000239157400053 PM 16825395 ER PT J AU Joffe, S Miller, FG AF Joffe, Steven Miller, Franklin G. TI Rethinking risk-benefit assessment for phase I cancer trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CLINICAL-TRIALS; ETHICAL CONSIDERATIONS; ANTICANCER AGENTS; ONCOLOGY TRIALS; CHILDREN; DESIGN; THERAPY; CONDUCT; CONSENT; DRUG C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA096872] NR 42 TC 42 Z9 43 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2006 VL 24 IS 19 BP 2987 EP 2990 DI 10.1200/JCO.2005.04.9296 PG 4 WC Oncology SC Oncology GA 063AC UT WOS:000238987200005 PM 16809725 ER PT J AU Sparano, JA Moulder, S Kazi, A Vahdat, L Li, T Pellegrino, C Munster, P Malafa, M Lee, D Hoschander, S Hopkins, U Hershman, D Wright, JJ Sebti, SM AF Sparano, Joseph A. Moulder, Stacy Kazi, Aslamuzzaman Vahdat, Linda Li, Tianhong Pellegrino, Christine Munster, Pam Malafa, Mokenge Lee, David Hoschander, Shira Hopkins, Una Hershman, Dawn Wright, John J. Sebti, Said M. TI Targeted inhibition of farnesyltransferase in locally advanced breast cancer: A phase I and II trial of tipifarnib plus dose-dense doxorubicin and cyclophosphamide SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 27th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX ID FARNESYL TRANSFERASE INHIBITOR; BIPOLAR SPINDLE FORMATION; RAS TRANSGENIC MICE; TUMOR-CELLS; R115777; CARCINOMAS; EXPRESSION; KINASE; P53; ACTIVATION AB Purpose To determine the recommended phase II dose (RPTD) of the farnesyltransferase (FTase) inhibitor tipifarnib when combined with doxorubicin and cyclophosphamide (AC) in patients with advanced breast cancer, the pathologic complete response (pCR) rate after preoperative treatment with four cycles of the combination in locally advanced breast cancer (LABC), and the effect of tipifarnib on primary tumor FTase enzyme activity in vivo. Patients and Methods Thirty-two patients with metastatic breast cancer (n = 11) or LABC (n = 21) received AC (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)) administered intravenously on day 1 plus tipifarnib (100, 200, or 300 mg bid for 6 to 14 days) without (n = 2) or with (n = 30) granulocyte colony-stimulating factor (G-CSF) for up to four cycles. Patients with LABC underwent surgery after up to four cycles of the combination. Results When combined with AC every 2 weeks plus G-CSF, the RPTD of tipifarnib was 200 mg bid administered on days 2 to 7. Seven (33%) of 21 patients (95% CI, 15% to 55%) with LABC treated with up to four cycles of the combination at the RPTD had a pCR in the breast at surgery. The five patients had serial biopsies that demonstrated at least 50% FTase enzyme inhibition in the primary tumor (median, 100%; range, 55% to 100%) after tipifarnib. Conclusion Tipifarnib may be safely combined with dose-dense AC using a dose and schedule that significantly inhibits FTase enzyme activity in human breast cancer in vivo and may enhance the pCR rate after four cycles of preoperative dose-dense AC. C1 Montefiore Med Ctr, Weiler Div, Dept Oncol, Albert Einstein Canc Ctr, Bronx, NY 10461 USA. Weill Cornell Med Ctr, New York, NY USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Breast Oncol Program, Tampa, FL 33612 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Weiler Div, Dept Oncol, Albert Einstein Canc Ctr, 2 S,Room 47-48,1825 Eastchester Rd, Bronx, NY 10461 USA. EM jsparano@montefiore.org FU NCI NIH HHS [N01 CM-17103, R01CA98473] NR 33 TC 35 Z9 37 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2006 VL 24 IS 19 BP 3013 EP 3018 DI 10.1200/JCO.2005.04.9114 PG 6 WC Oncology SC Oncology GA 063AC UT WOS:000238987200009 PM 16769985 ER PT J AU Huang, BJ Dawson, DA Stinson, FS Hasin, DS Ruan, WJ Saha, TD Smith, SM Goldstein, RB Grant, BF AF Huang, Boji Dawson, Deborah A. Stinson, Frederick S. Hasin, Deborah S. Ruan, W. June Saha, Tulshi D. Smith, Sharon M. Goldstein, Rise B. Grant, Bridget F. TI Prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders in the United States: Results of the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; DSM-IV ALCOHOL; PERSONALITY-DISORDERS; ILLICIT USE; ANXIETY DISORDERS; COLLEGE-STUDENTS; MENTAL-DISORDERS; CHRONIC PAIN AB Objective: To present national data on the prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders for sedatives, tranquilizers, opioids, and amphetamines. Method: Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a face-to-face nationally representative survey of 43,093 adults conducted during 2001 and 2002. Results: Lifetime prevalences of nonmedical use of sedatives, tranquilizers, opioids, and amphetamines were 4.1%, 3.4%, 4.7%, and 4.7%, respectively. Corresponding rates of abuse and/or dependence on these substances were 1.1%, 1.0%, 1.4%, and 2.0%. The odds of nonmedical prescription drug use and drug use disorders were generally greater among men, Native Americans, young and middle-aged, those who were widowed/separated/divorced or never married, and those residing in the West. Abuse/dependence liability was greatest for amphetamines, and nonmedical prescription drug use disorders were highly comorbid with other Axis I and II disorders. The majority of individuals with nonmedical prescription drug use disorders never received treatment. Conclusions: Nonmedical prescription drug use and disorders are pervasive in the U.S. population and highly comorbid with other psychiatric disorders. Native Americans had significantly greater rates of nonmedical prescription drug use and drug use disorders, highlighting the need for culturally-sensitive prevention and intervention programs. Unprecedented comorbidity between nonmedical prescription drug use disorders and between nonmedical prescription drug use disorders and illicit drug use disorders suggests that the typical individual abusing or dependent on these drugs obtained them illegally, rather than through a physician. Amphetamines had the greatest abuse/dependence liability, and recent increases in the potency of illegally manufactured amphetamines may portend an epidemic in the youngest NESARC cohort. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol & Psychiat, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Rm 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS; NIAAA NIH HHS [K05 AA 014223] NR 58 TC 173 Z9 173 U1 2 U2 18 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2006 VL 67 IS 7 BP 1062 EP 1073 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 070TU UT WOS:000239548300008 PM 16889449 ER PT J AU Emerson, SU Nguyen, H Torian, U Purcell, RH AF Emerson, S. U. Nguyen, H. Torian, U. Purcell, R. H. TI Analysis of hepatitis E virus mutants in a new cell culture system SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S9 EP S9 DI 10.1016/S1386-6532(06)80038-7 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300029 ER PT J AU Graff, J Torian, U Nguyen, H Emerson, S AF Graff, J. Torian, U. Nguyen, H. Emerson, S. TI Hepatitis E virus ORF2 and ORF3 proteins are encoded by a bicistronic subgenomic mRNA SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIAID, LID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S9 EP S10 DI 10.1016/S1386-6532(06)80039-9 PG 2 WC Virology SC Virology GA 064CR UT WOS:000239067300030 ER PT J AU Hoofnagle, JH AF Hoofnagle, J. H. TI Therapy of hepatitis B. Overview SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIH, Liver Dis Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S46 EP S47 DI 10.1016/S1386-6532(06)80144-7 PG 2 WC Virology SC Virology GA 064CR UT WOS:000239067300135 ER PT J AU Kato, T Liang, TJ AF Kato, T. Liang, T. J. TI Production of infectious hepatitis C virus of various genotypes in cell culture SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S53 EP S53 DI 10.1016/S1386-6532(06)80162-9 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300153 ER PT J AU Kirk, GD Kuniholm, MH Lesi, OA Mendy, M Akano, AC Goedert, JJ Whittle, H Hainaut, P Montesano, R AF Kirk, G. D. Kuniholm, M. H. Lesi, O. A. Mendy, M. Akano, A. C. Goedert, J. J. Whittle, H. Hainaut, P. Montesano, R. TI Risk of cirrhosis with exposure to aflatoxin and hepatitis B and C viruses SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. MRC Labs, Gambia Hepatitis Intervent Study, Banjul, Gambia. Natl Hosp, Dept Radiodiag, Abuja, Nigeria. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. IARC, Gambia Hepatitis Intervent Study, Lyon, France. RI Kirk, Gregory/A-8484-2009; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S37 EP S38 DI 10.1016/S1386-6532(06)80119-8 PG 2 WC Virology SC Virology GA 064CR UT WOS:000239067300110 ER PT J AU Purcell, RH Yu, C McDonald, S Emerson, SU AF Purcell, R. H. Yu, C. McDonald, S. Emerson, S. U. TI Comparative pathogenesis of viral hepatitis SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S194 EP S194 DI 10.1016/S1386-6532(06)80603-7 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300593 ER PT J AU Purcell, RH AF Purcell, R. H. TI Hepatitis E: light at the end of the tunnel? SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIAID, LID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S1 EP S1 DI 10.1016/S1386-6532(06)80013-2 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300004 ER PT J AU Rehermann, B AF Rehermann, B. TI Innate and adaptive immune responses to HCV SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S21 EP S22 DI 10.1016/S1386-6532(06)80074-0 PG 2 WC Virology SC Virology GA 064CR UT WOS:000239067300065 ER PT J AU Shata, MT Barrett, A Rouster, S Shire, NJ Blackard, JT Atiq, M Engle, R Purcell, R Emerson, S Strickland, GT Sherman, KE AF Shata, M. T. Barrett, A. Rouster, S. Shire, N. J. Blackard, J. T. Atiq, M. Engle, R. Purcell, R. Emerson, S. Strickland, G. T. Sherman, K. E. TI Isolation and characterization of hepatitis E virus (HEV)-specific T cell clones from an asymptomatic HEV-exposed subject SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 Univ Cincinnati, Div Digest Dis, Cincinnati, OH USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S158 EP S158 DI 10.1016/S1386-6532(06)80488-9 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300478 ER PT J AU Zhou, Y Emerson, SU AF Zhou, Y. Emerson, S. U. TI Heat shock cognate protein 70 may mediate the entry of hepatitis E virus into host cells SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S155 EP S155 DI 10.1016/S1386-6532(06)80480-4 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300470 ER PT J AU Cicerone, K Levin, H Malec, J Stuss, D Whyte, J AF Cicerone, Keith Levin, Harvey Malec, James Stuss, Donald Whyte, John TI Cognitive rehabilitation interventions for executive function: Moving from bench to bedside in patients with traumatic brain injury SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID CLOSED-HEAD-INJURY; FRONTAL-LOBE; WORKING-MEMORY; PREFRONTAL CORTEX; GOAL MANAGEMENT; AXONAL INJURY; DEFICITS; PERFORMANCE; DISTURBANCE; ATTENTION AB Executive function mediated by prefrontally driven distributed networks is frequently impaired by traumatic brain injury (TBI) as a result of diffuse axonal injury and focal lesions. In addition to executive cognitive functions such as planning and working memory, the effects of TBI impact social cognition and motivation processes. To encourage application of cognitive neuroscience methods to studying recovery from TBI, associated reorganization of function, and development of interventions, this article reviews the pathophysiology of TBI, critiques currently employed methods of assessing executive function, and evaluates promising interventions that reflect advances in cognitive neuroscience. Brain imaging to identify neural mechanisms mediating executive dysfunction and response to interventions following TBI is also discussed. C1 Baylor Coll Med, Houston, TX 77030 USA. Mayo Clin, Rochester, MN 55905 USA. Univ Toronto, Toronto, ON, Canada. Moss Rehabil Res Inst, Philadelphia, PA USA. RP Cicerone, K (reprint author), NINDS, 6001 Execut Blvd,Room 3305, Bethesda, MD 20892 USA. NR 63 TC 103 Z9 103 U1 3 U2 26 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 2006 VL 18 IS 7 BP 1212 EP 1222 DI 10.1162/jocn.2006.18.7.1212 PG 11 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 064MM UT WOS:000239093800014 PM 16839293 ER PT J AU Barrett, AM Buxbaum, LJ Coslett, HB Edwards, E Heilman, KM Hillis, AE Milberg, WP Robertson, IH AF Barrett, Anna M. Buxbaum, Laurel J. Coslett, H. Branch Edwards, Emmeline Heilman, Kenneth M. Hillis, Argye E. Milberg, William P. Robertson, Ian H. TI Cognitive rehabilitation interventions for neglect and related disorders: Moving from bench to bedside in stroke patients SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Review ID UNILATERAL SPATIAL NEGLECT; RIGHT-HEMISPHERE STROKE; MOTOR-INTENTIONAL NEGLECT; DOPAMINE AGONIST THERAPY; LEFT HEMISPATIAL NEGLECT; RIGHT BRAIN-DAMAGE; VISUAL NEGLECT; DIRECTIONAL HYPOKINESIA; VIRTUAL-REALITY; VISUOSPATIAL NEGLECT AB The spatial neglect syndrome. defined by asymmetric attention and action not attributed to primary motor or sensory dysfunction and accompanied by functional disability, is a major cause of post-stroke morbidity. In this review. We consider the challenges and obstacles Facing scientific researches Wishing to evaluate the mechanisms and effectiveness of rehabilitation interventions. Spatial neglect is a heterogeneous disorder, for which consensus research definitions are not currently available, and it is unclear which of the deficits associated with the syndrome causes subsequent disability. We review current opinion about methods of assessment, suggest a rational approach to selecting therapies which requires further study, and make systems-level and theoretical recommendations for building theory. We lastly review some creative questions for consideration in future research. C1 NINDS, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Moss Rehabil Res Inst, Philadelphia, PA 19104 USA. Kessler Med Rehabil Res & Educ Corp, W Orange, NJ USA. Univ Florida, Sch Med, Gainesville, FL USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Dublin Trinity Coll, Dublin 2, Ireland. RP Edwards, E (reprint author), NINDS, 6001 Execut Blvd,Room 3305, Bethesda, MD 20892 USA. EM ee48r@nih.gov OI Barrett, A.M./0000-0002-0789-2887; Robertson, Ian H/0000-0001-8637-561X FU NINDS NIH HHS [K02 NS047099, K08 NS002085, R01 NS047691] NR 127 TC 63 Z9 67 U1 3 U2 26 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 2006 VL 18 IS 7 BP 1223 EP 1236 DI 10.1162/jocn.2006.18.7.1223 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 064MM UT WOS:000239093800015 PM 16839294 ER PT J AU Bartel, DL Sullivan, SL Lavoie, EG Sevigny, J Finger, TE AF Bartel, DL Sullivan, SL Lavoie, EG Sevigny, J Finger, TE TI Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE gustatory; ecto-ATPase; NTPDase2; ear; ATP signaling; mouse; taste bud ID CIRCUMVALLATE PAPILLAE; ADENOSINE RECEPTORS; GENE-EXPRESSION; FINE STRUCTURE; RAT-BRAIN; MOUSE; LOCALIZATION; NTPDASE2; IMMUNOLOCALIZATION; THROMBOREGULATION AB The presence of one or more calcium-dependent ecto-ATPases (enzymes that hydrolyze extracellular 5'-triphosphates) in mammalian taste buds was first shown histochemically. Recent studies have established that dominant ecto-ATPases consist of enzymes now called nucleoside triphosphate diphosphohydrolases (NTPDases). Massively parallel signature sequencing (MPSS) from murine taste epithelium provided molecular evidence suggesting that NTPDase2 is the most likely member present in mouse taste papillae. Immunocytochemical and enzyme histochemical staining verified the presence of NTPDase2 associated with plasma membranes in a large number of cells within all mouse taste buds. To determine which of the three taste cell types expresses this enzyme, double-label assays were performed with antisera directed against the glial glutamate/aspartate transporter (GLAST), the transduction pathway proteins phospholipase C beta 2 (PLC beta 2) or the G-protein subunit a-gustducin, and serotonin (5HT) as markers of type I, II, and III taste cells, respectively. Analysis of the double-labeled sections indicates that NTPDase2 immunoreactivity is found on cell processes that often envelop other taste cells, reminiscent of type I cells. In agreement with this observation, NTPDase2 was located to the same membrane as GLAST, indicating that this enzyme is present in type I cells. The presence of ecto-ATPase in taste buds likely reflects the importance of ATP as an intercellular signaling molecule in this system. C1 UCDHSC, Dept Cell & Dev Biol, Rocky Mt Taste & Smell Ctr, Aurora, CO 80045 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Univ Laval, Ctr Rech Rhumatol & Immunol, Quebec City, PQ G1V 4G2, Canada. RP Finger, TE (reprint author), UCDHSC, Dept Cell & Dev Biol, Rocky Mt Taste & Smell Ctr, Mail Stop 8108,POB 6511, Aurora, CO 80045 USA. EM tom.finger@uchsc.edu RI Sevigny, Jean/E-8039-2012; OI Sevigny, Jean/0000-0003-2922-1600; Finger, Thomas/0000-0001-5923-5099 FU Canadian Institutes of Health Research [49460]; Intramural NIH HHS; NIDCD NIH HHS [P30 DC004657, DC006070, DC07495, P30 DC004657-029002, P30 DC04657, R01 DC006070, R01 DC006070-02, R01 DC007495, R01 DC007495-01A1] NR 54 TC 132 Z9 140 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 1 PY 2006 VL 497 IS 1 BP 1 EP 12 DI 10.1002/cne.20954 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 047YP UT WOS:000237914900001 PM 16680780 ER PT J AU Tuan, E Kirk, KL AF Tuan, Edward Kirk, Kenneth L. TI Fluorine reactivity in difluoromethylimidazoles SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE imidazoles; fluoride loss; base sensitivity ID INDOLES AB A difluoromethyl substituent attached directly to an imidazole ring is very reactive toward basic hydrolysis. A correlation of rate of fluoride loss with increasing pH is consistent with a mechanism that involves initial ionization of the imidazole NH, formation of an intermediate azafulvene by loss of HF, and reaction of the intermediate with solvent water. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov NR 20 TC 3 Z9 3 U1 2 U2 3 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD JUL PY 2006 VL 127 IS 7 BP 980 EP 982 DI 10.1016/j.jfluchem.2006.03.014 PG 3 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 061VO UT WOS:000238901300026 ER PT J AU Nguyen, KV Sharlef, FS Chan, SSL Copeland, WC Naviaux, RK AF Nguyen, Khue V. Sharlef, Farida S. Chan, Sherine S. L. Copeland, William C. Naviaux, Robert K. TI Molecular diagnosis of Alpers syndrome SO JOURNAL OF HEPATOLOGY LA English DT Article DE Alpers-Huttenlocher syndrome; POLG; mtDNA depletion; seizures; cirrhosis ID DNA-POLYMERASE-GAMMA; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; DEOXYGUANOSINE KINASE GENE; BASE EXCISION-REPAIR; MITOCHONDRIAL-DNA; POLG MUTATIONS; ACCESSORY SUBUNIT; NEURONAL DEGENERATION; DEPLETION; ATAXIA AB Background/Aims: Alpers syndrome is a developmental mitochondrial DNA depletion syndrome leading to fatal brain and liver disease in children and young adults. Mutations in the gene for the mitochondrial DNA polymerase (POLG) have recently been shown to cause this disorder. Methods: The POLG locus was sequenced in 15 sequential probands diagnosed with Alpers syndrome. In addition, the POLG mutations found to cause Alpers syndrome in the 20 cases published to date were analyzed. Results: POLG DNA testing accurately diagnosed 87% (13/15 = 87%: 95% confidence interval = 60-98%) of cases. Five new POLG amino acid substitutions (F749S, R852C, T914P, L966R, and L1173fsX) were found that were associated with Alpers syndrome in five unrelated kindreds, and 14 different allelic combinations of POLG mutations were found to cause Alpers syndrome in the 20 probands published to date. The most common Alpers-causing mutation was the A467T substitution, located in the linker region of the pol gamma protein, which accounted for about 40% of the alleles and was present in 65% of the patients. All patients with POLG mutations had either the A467T or the W748S substitution in the linker region. Conclusions: Screening for A467T and W748S substitutions in POLG now constitutes the most rapid and sensitive test available for confirming the clinical diagnosis of Alpers syndrome. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Univ Calif San Diego, San Diego Sch Med, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, San Diego Sch Med, Dept Pediat, San Diego, CA 92103 USA. Univ Calif San Diego, San Diego Sch Med, Mitochondrial & Metab Dis Ctr, San Diego, CA 92103 USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Naviaux, RK (reprint author), Univ Calif San Diego, San Diego Sch Med, Dept Med, Bldg CTF,Rm C-103,214 Dickinson St, San Diego, CA 92103 USA. EM naviaux@ucsd.edu NR 41 TC 75 Z9 75 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUL PY 2006 VL 45 IS 1 BP 108 EP 116 DI 10.1016/j.jhep.2005.12.026 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 060DK UT WOS:000238782200014 PM 16545482 ER PT J AU Liu, LP Graham, GJ Damodaran, A Hu, TF Lira, SA Sasse, M Canasto-Chibuque, C Cook, DN Ransohoff, RM AF Liu, LP Graham, GJ Damodaran, A Hu, TF Lira, SA Sasse, M Canasto-Chibuque, C Cook, DN Ransohoff, RM TI Cutting edge: The silent chemokine receptor D6 is required for generating T cell responses that mediate experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY CC CHEMOKINES; DECOY; MICE AB D6, a promiscuous nonsignaling chemokine binding molecule expressed on the lymphatic endothelium, internalizes and degrades CC chemokines, and D6(-/-) mice demonstrated increased cutaneous inflammation following topical phorbol ester or CFA injection. We report that D6(-/-) mice were unexpectedly resistant to the induction of experimental autoimmune encephalomyelitis due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) piptide 35-55 in CFA, D6(-/-) mice showed reduced spinal cord inflammation and demyelination with lower incidence and severity of experimental autoimmune encephalomyelitis attacks as compared with De(+/+) littermates. In adoptive transfer studies, MOG-primed De(+/-) T cells equally mediated disease in D6(+/+) or D6(-/-) mice, whereas cells from D6(-/-) mice transferred disease Poorly to D6(+/-) recipients. Lymph node cells from MOG-primed D6(-/-) mice showed weak proliferative responses and made reduced IFN-gamma but normal IL-5. CD11c(+) dendritic cells accumulated abnormally in cutaneous immunization sites of D6(-)/(-) mice. Surprisingly, D6, a "silent" chemokine receptor, supports immune response generation. C1 Cleveland Clin Fdn, Neuroinflammat Res Ctr, Dept Neurosci, Lerner Res Inst, Cleveland, OH 44195 USA. Univ Glasgow, Div Immunol Infect & Inflammat, Glasgow, Lanark, Scotland. Univ So Calif, Los Angeles, CA 90089 USA. Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Ransohoff, RM (reprint author), Cleveland Clin Fdn, Neuroinflammat Res Ctr, Dept Neurosci, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM ransohr@ccf.org RI Graham, Gerard/D-1240-2009 FU NINDS NIH HHS [3R01 NS 32151] NR 13 TC 46 Z9 50 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2006 VL 177 IS 1 BP 17 EP 21 PG 5 WC Immunology SC Immunology GA 055ST UT WOS:000238471400004 PM 16785491 ER PT J AU Liu, CH Fan, YT Dias, A Esper, L Corn, RA Bafica, A Machado, FS Aliberti, J AF Liu, CH Fan, YT Dias, A Esper, L Corn, RA Bafica, A Machado, FS Aliberti, J TI Cutting edge: Dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA-INTERFERON; T-CELLS; INTERLEUKIN-12; STIMULATION; PROVIDES AB A powerful IFN-gamma response is triggered upon infection with the protozoan parasite, Toxoplasma gondii. Several cell populations, including dendritic cells (DO), macrophages, and neutrophils, produce IL-12, a key cytokine for IFN-gamma induction. However, it is still unclear which of the above cell populations is its main source. Diphtheria toxin (D T) injection causes transient DC depletion in a transgenic mouse expressing Simian DT receptors under the control of the CD11c promoter, allowing us to investigate the role of DCs in IL-12 production. T. gondii-inoculated DT-treated and control groups were monitored for IL-12 levels and survival We show in this study that DC depletion abolished IL-12 production and led to mortality. Furthermore, replenishment with wild-type, hut not MyD88- or IL-12p35-deficient, DCs rescued IL-12 production, IFN-gamma-induction, and resistance to infection in DC-depleted mice. Taken together, the results presented in this study indicate that DCs constitute the major IL12-producing cell population in vivo during T. gondii infection. C1 Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. Childrens Hosp, Med Ctr, Div Mol Immunobiol, Cincinnati, OH 45229 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Fdn Oswaldo Cruz, Lab Imunobiol, Inst Goncalo Moniz, Salvador, BA, Brazil. RP Aliberti, J (reprint author), Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA. EM julio.aliberti@cchmc.org RI minor, radiah/B-6412-2012; Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 20 TC 112 Z9 119 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2006 VL 177 IS 1 BP 31 EP 35 PG 5 WC Immunology SC Immunology GA 055ST UT WOS:000238471400007 PM 16785494 ER PT J AU Qian, SB Reits, E Neefjes, J Deslich, JM Bennink, JR Yewdell, JW AF Qian, Shu-Bing Reits, Eric Neefjes, Jacques Deslich, Jeanne M. Bennink, Jack R. Yewdell, Jonathan W. TI Tight linkage between translation and MHC class I peptide ligand generation implies specialized antigen processing for defective ribosomal products SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEWLY SYNTHESIZED PROTEINS; ENDOPLASMIC-RETICULUM; PROTEASOMAL DEGRADATION; MAMMALIAN-CELLS; DENDRITIC CELLS; MOLECULES; LOCALIZATION; TYROSINASE; NUCLEAR; PATHWAY AB There is mounting evidence that MHC class I peptide ligands are predominantly generated from defective ribosomal products and other classes of polypeptides degraded rapidly (t(1/2) < 10 min) following their synthesis. The most direct eviden supporting this conclusion is the rapid inhibition of peptide ligand generation following cyclobeximide-mediated inhibition of protein synthesis. In this study, we show that this linkage is due to depleting the pool of rapidly degraded proteins, and not to interference with other protein synthesis-dependent processes. Our findings indicate that in the model systems used in this study, MHC class I peptides are preferentially generated from rapidly degraded polypeptides relative to slowly degraded proteins. This conclusion is supported by the properties of peptide presentation from slowly degraded (t(1/2) = 4 h) defective ribosomal products generated artificially by incorporation of the amino acid analog canavanine into a model viral Ag. We propose that specialized machinery exists to link protein synthesis with class I peptide ligand generation to enable the rapid detection of viral gene expression. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Netherlands Canc Inst, Div Tumor Biol, Amsterdam, Netherlands. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS NR 33 TC 49 Z9 49 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2006 VL 177 IS 1 BP 227 EP 233 PG 7 WC Immunology SC Immunology GA 055ST UT WOS:000238471400031 PM 16785518 ER PT J AU Rallabhandi, P Bell, J Boukhvalova, MS Medvedev, A Lorenz, E Arditi, M Hemming, VG Blanco, JCG Segal, DM Vogel, SN AF Rallabhandi, P Bell, J Boukhvalova, MS Medvedev, A Lorenz, E Arditi, M Hemming, VG Blanco, JCG Segal, DM Vogel, SN TI Analysis of TLR4 polymorphic variants: New insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-4; RESPIRATORY SYNCYTIAL VIRUS; INFLAMMATORY-BOWEL-DISEASE; LIGAND-BINDING DOMAIN; GENE-EXPRESSION; LIPOPOLYSACCHARIDE-BINDING; ASP299GLY POLYMORPHISM; RHEUMATOID-ARTHRITIS; MURINE MACROPHAGES; ULCERATIVE-COLITIS AB TLR4 is the signal-transducing receptor for structurally diverse microbial molecules such as bacterial LPS, respiratory syncytial virus fusion (F) protein, and chlamydial heat shock protein 60. Previous studies associated two polymorphic mutations in the extracellular domain of TLR4 (ASp(299)Gly and Thr(399)IIe) with decreased LPS responsiveness. To analyze the molecular basis for diminished responsiveness, site-specific mutations (singly or coexpressed) were introduced into untagged and epitope (Flag)-tagged wild-type (WT) TLR4 expression vectors to permit a direct comparison of WT and mutant signal transduction. Coexpression of WT TLR4, CD14, and MD-2 expression vectors in HEK293T cells was first optimized to achieve optimal LPS-induced NF-kappa B reporter gene expression. Surprisingly, transfection of cells with MD-2 at high input levels often used in the literature suppressed LPS-induced signaling, whereas supraoptimal CD14 levels did not. Under conditions where WT and polymorphic variants were comparably expressed, significant differences in NF-kappa B activation were observed in response to LPS and two structurally unrelated TLR4 agonists, chlamydial heat shock protein 60 and RSV F protein, with the double, cosegregating mutant TLR4 exhibiting the greatest deficiency. Overexpression of Flag-tagged WT and mutant vectors at input levels resulting in agonist-independent signaling led to equivalent NF-kappa B signaling, suggesting that these mutations in TLR4 affect appropriate interaction with agonist or coreceptor. These data provide new insights into the importance of stoichiometry among the components of the TLR4/MD2/CD14 complex. A structural model that accounts for the diminished responsiveness of mutant TLR4 polymorphisms to structurally unrelated TLR4 agonists is proposed. C1 Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20814 USA. Virion Syst, Rockville, MD 20850 USA. Univ N Carolina, Thurston Arthritis Res Ctr, Chapel Hill, NC 27599 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20814 USA. RP Vogel, SN (reprint author), Univ Maryland, Dept Microbiol & Immunol, 660 W Redwood St,Howard Hall Bldg,Room HH 324, Baltimore, MD 21201 USA. EM svogel@som.umaryland.edu RI Bell, Jessica/I-3893-2013 OI Bell, Jessica/0000-0003-1455-3274 FU Intramural NIH HHS; NIAID NIH HHS [AI 057575, AI 058128, AI 059524, AI 18797] NR 58 TC 142 Z9 152 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2006 VL 177 IS 1 BP 322 EP 332 PG 11 WC Immunology SC Immunology GA 055ST UT WOS:000238471400041 PM 16785528 ER PT J AU Asokan, R Hua, J Young, KA Gould, HJ Hannan, JP Kraus, DM Szakonyi, G Grundy, GJ Chen, XJS Crow, MK Holers, VM AF Asokan, R Hua, J Young, KA Gould, HJ Hannan, JP Kraus, DM Szakonyi, G Grundy, GJ Chen, XJS Crow, MK Holers, VM TI Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-alpha: A potential role in systemic lupus erythematosus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; CD21 LIGAND-BINDING; HUMAN B-LYMPHOCYTES; NF-KAPPA-B; C3D RECEPTOR; I INTERFERON; MONOCLONAL-ANTIBODY; NATURAL ANTIBODY; CELL ACTIVATION; MICE DEFICIENT AB Human complement receptor type 2 (CR2/CD21) is a B lymphocyte membrane glycoprotein that plays a central role in the immune responses to foreign Ags as well as the development of autoimmunity to nuclear Ags in systemic lupus erythematosus. In addition to these three well-characterized ligands, C3d/iC3b, EBV-gp350, and CD23, a previous study has identified CR2 as a potential receptor for IFN-alpha. IFN-alpha, a multifunctional cytokine important in the innate immune system, has recently been proposed to play a major pathogenic role in the development of systemic lupus erythematosus in humans and mice. In this study, we have shown using surface plasmon resonance and ELISA approaches that CR2 will bind IFN-a in the same affinity range as the other three well-characterized ligands studied in parallel. In addition, we show that IFN-a interacts with short consensus repeat domains 1 and 2 in a region that serves as the ligand binding site for Cd3/iC3b, EBV-gp350, and CD23. Finally, we show that treatment of purified human peripheral blood B cells with the inhibitory anti-CR2 mAb 171 diminishes the induction of IFN-alpha-responsive genes. Thus, IFN-alpha represents a fourth class of extracellular ligands for CR2 and interacts with the same domain as the other three ligands. Defining the role of CR2 as compared with, the well-characterized type 1 IFN-a receptor I and 2 in mediating innate immune and autoimmune roles of this cytokine should provide additional insights into the biologic roles of this interaction. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Rheumatol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Hosp Special Surg, Mary Kirkland Ctr Lupus Res Hosp, New York, NY 10021 USA. Univ London Kings Coll, Randall Ctr Mol Mech Cell Funct, London WC2R 2LS, England. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Holers, VM (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Div Rheumatol, Box B-115,4200 E 9th Ave, Denver, CO 80262 USA. EM Michael.Holers@UCHSC.edu FU Medical Research Council [G0200486]; NCI NIH HHS [R01 CA 53615]; NIAMS NIH HHS [R01 AR 050829] NR 69 TC 54 Z9 55 U1 1 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2006 VL 177 IS 1 BP 383 EP 394 PG 12 WC Immunology SC Immunology GA 055ST UT WOS:000238471400047 PM 16785534 ER PT J AU Card, JW Carey, MA Bradbury, JA DeGraff, LM Morgan, DL Moorman, MP Flake, GP Zeldin, DC AF Card, JW Carey, MA Bradbury, JA DeGraff, LM Morgan, DL Moorman, MP Flake, GP Zeldin, DC TI Gender differences in murine airway responsiveness and lipopolysaccharide-induced inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNTHASE-DEFICIENT MICE; ACUTE LUNG INJURY; INHALED LIPOPOLYSACCHARIDE; TESTOSTERONE; ASTHMA; RATS; ESTRADIOL; RESPONSES; ESTROGEN; HORMONES AB The roles of gender and sex hormones in lung function and disease are complex and not completely understood. The present study examined the influence. of gender on lung function and respiratory mechanics in naive mice and on acute airway inflammation and hyperresponsiveness induced by intratracheal LPS administration. Basal lung function characteristics did not differ between naive males and females, but males demonstrated significantly greater airway responsiveness than females following aerosolized methacholine challenge as evidenced by increased respiratory system resistance and elastance (p < 0.05). Following LPS administration, males developed more severe hypothermia and greater airway hyperresponsiveness than females (p < 0.05). Inflammatory indices including bronchoalveolar lavage fluid total cells, neutrophils, and TNF-alpha content were greater in males than in females 6 h following LPS administration (p < 0.05), whereas whole-lung TLR-4 protein levels did not differ among treatment groups, suggesting that differential expression of TLR-4 before or after LPS exposure did not underlie the observed inflammatory outcomes. Gonadectomy decreased airway inflammation in males but did not alter inflammation in females, whereas administration of exogenous testosterone to intact females increased their inflammatory responses to levels observed in intact males. LPS-induced airway hyperresponsiveness was also decreased in castrated males and was increased in females administered exogenous testosterone. Collectively, these data indicate that airway responsiveness in naive mice is influenced by gender, and that male mice have exaggerated airway inflammatory and functional responses to LPS compared with females. These gender differences are mediated, at least in part, by effects of androgens. C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101885-03] NR 26 TC 81 Z9 82 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 JUL 1 PY 2006 VL 177 IS 1 BP 621 EP 630 PG 10 WC Immunology SC Immunology GA 055ST UT WOS:000238471400073 PM 16785560 ER PT J AU Zhao, YB Zheng, ZL Khong, HT Rosenberg, SA Morgan, RA AF Zhao, YB Zheng, ZL Khong, HT Rosenberg, SA Morgan, RA TI Transduction of an HLA-DP4-restricted NY-ESO-1-specific TCR into primary human CD4(+) lymphocytes SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE NY-ESO-1; HLA-DP4; TCR; retroviral vector; gene transfer ID MHC CLASS-II; REGULATORY T-CELLS; TESTIS ANTIGEN NY-ESO-1; ERADICATION IN-VIVO; METASTATIC MELANOMA; TUMOR-IMMUNITY; DENDRITIC CELLS; CANCER-PATIENTS; ADOPTIVE IMMUNOTHERAPY; ESTABLISHED TUMORS AB cDNAs encoding functional T cell receptor (TCR) alpha and beta chains from a CD4(+) T cell line (SG6) generated by repeated stimulation of a melanoma patient's peripheral blood mononuclear cells with HLA-DP4-restricted, NY-ESO-1-specific peptide p161-180 were cloned using a 5'rapid amplification of cDNA end method. Three different TCR alpha chains and 7 TCR beta chains were found among the 84 alpha and 162 beta cDNA clones tested. By screening different combination of the alpha/beta chains using RNA electroporation, TRAV9-1 (V alpha 22.1) and TRBV20-1 (V beta 2) were found to be the functional pair in line SG6. Antibody blocking experiments confirmed that the specificity of TRAV9-1/TRBV20-1 mRNA-transfected T cells were CD4 dependent and HLA-DP4 restricted. A retroviral vector expressing both TRAV9-1 and TRBV20-1 was constructed and used for transduction of OKT3-stimulated peripheral blood lymphocytes from melanoma patients. TCR-transduced CD4 T cells were capable of recognizing peptide-pulsed antigen-presenting cells (Epstein-Barr virus transformed B-cells, dendritic cells, and peripheral blood mononuclear cells), and protein-pulsed dendritic cells. Transduced cells were also capable of proliferation upon peptide stimulation and recognized peptide concentrations that were recognized by the parental line (0.2 mu M). In contrast to SG6, which could not recognize human tumors, TCR-transduced CD4 T cells could specifically recognize NY-ESO-1/HLA-DP4-expressing melanoma cells. Major histocompatibility complex class II TCR-transduced CD4 T cells provides an alternative source of tumor antigen-specific T cells for adoptive immunotherapy of cancer patients. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), 10 Ctr Dr,Bldg 10,Rm 3-5940, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 SC003811-31] NR 54 TC 14 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2006 VL 29 IS 4 BP 398 EP 406 DI 10.1097/01.cji.0000203082.20365.7f PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 056EX UT WOS:000238505300006 PM 16799335 ER PT J AU Melenhorst, JJ Solomon, SR Shenoy, A Hensel, NF McCoy, JP Keyvanfar, K Barrett, AJ AF Melenhorst, JJ Solomon, SR Shenoy, A Hensel, NF McCoy, JP Keyvanfar, K Barrett, AJ TI Robust expansion of viral antigen-specific CD4(+) and CD8(+) T cells for adoptive T cell therapy using gene-modified activated T cells as antigen presenting cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cytomegalovirus; T cells; adoptive immunotherapy; antigen-presenting cells; gene transfer ID PREVENT CYTOMEGALOVIRUS DISEASE; LYMPHOCYTE CTL RESPONSE; MYELOID-LEUKEMIA; IN-VITRO; SELECTIVE DEPLETION; DONOR LYMPHOCYTES; HIGH-FREQUENCIES; DENDRITIC CELLS; CLINICAL-SCALE; CD8+T CELLS AB Cytomegalovirus (CMV) reactivation after stem cell transplantation can be treated with CMV-specific T cells, but current in vitro techniques using dendritic cells as antigen-presenting cells are time-consuming and expensive. To simplify the production of clinical grade CMV-specific T cells, we evaluated gene-modified activated T cells [antigen presenting T cells (T-APCs)] as a reliable and easily produced source of APCs to boost CD4(+) and CD8(+) T-cell responses against the immunodominant CMV antigen pp65. T-APCs expressing the full-length immunodominant CMV pp65 gene were used to stimulate the expansion of autologous T cells. After 10 to 14 days, the T cell lines were tested for antigen specificity by using the flow cytometric intracellular detection of interferon-gamma after stimulation for 6 hours with a pp65 peptide library of 15-mers, overlapping by 11 amino acids. Under optimal conditions, this technique induced a median 766-fold and a 652-fold expansion of pp65-specific CD4(+) and CD8(+) responder cells, respectively, in 15 T cell lines. In 13 of 15 T cell lines, over 10(6) antigen-specific CD4(+) plus CD8(+) T cells were generated starting with only 5 x 10(6) peripheral blood mononuclear cells, representing an over 3-log increase. These data indicate that T-APCs efficiently boost pp65-specific CD4(+) and CD8(+) T cell numbers to clinically useful levels. The approach has the advantage of using a single leukocyte collection from the donor to generate large numbers of CMV-specific T cells within a total 3-week culture period using only one stimulation of antigen. C1 NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Melenhorst, JJ (reprint author), NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bldg 10-CRC,Room 3-5320,10 Ctr Dr, Bethesda, MD 20892 USA. EM melenhoj@nhlbi.nih.gov NR 45 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2006 VL 29 IS 4 BP 436 EP 443 DI 10.1097/01.cji.0000211302.52503.93 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 056EX UT WOS:000238505300010 PM 16799339 ER PT J AU Maker, AV Yang, JC Sherry, RM Topalian, SL Kannula, US Royal, RE Hughes, M Yellin, MJ Haworth, LR Levy, C Allen, T Mavroukakis, SA Attia, P Rosenberg, SA AF Maker, AV Yang, JC Sherry, RM Topalian, SL Kannula, US Royal, RE Hughes, M Yellin, MJ Haworth, LR Levy, C Allen, T Mavroukakis, SA Attia, P Rosenberg, SA TI Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE autoimmunity; human; tunor immunity; cell activation; T-cells ID REGULATORY T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLONY-STIMULATING FACTOR; ANTIGEN 4 CTLA-4; CTLA-4-MEDIATED INHIBITION; COMBINATION IMMUNOTHERAPY; LYMPHOCYTE ANTIGEN-4; TUMOR-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; CANCER REGRESSION AB We previously reported our experience in treating 56 patients with metastatic melanoma using a human anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody. Durable tumor regressions were seen that correlated with the induction of autoimmune toxicities. In this study, we treated 46 additional patients using an intrapatient dose escalation schema to test whether higher doses of anti-CTLA-4 antibody would induce increased autoimmunity and concomitant tumor regression. Twenty-three patients started anti-CTLA-4 antibody administration at 3 mg/kg and 23 patients started treatment at 5 mg/kg, receiving doses every 3 weeks. Patients were dose-escalated every other. dose to a maximum of 9 mg/kg or until objective clinical responses or grade III/TV autoimmune toxicity were seen. Escalating doses of antibody resulted in proportionally higher plasma concentrations. Sixteen patients (35%) experienced a grade III/IV autoimmune toxicity. Five patients (11%) achieved an objective clinical response. Two of the responses are ongoing at 13 and 16 months, respectively. Flow cytometric analysis of peripheral blood revealed significant increases in both T-cell surface markers of activation and memory phenotype. Thus, higher serum levels and prolonged administration of anti-CTLA-4 antibody resulted in a trend toward a greater incidence of grade III/IV autoimmune toxicity than previously reported, but did not seem to increase objective response rates. C1 NCI, Surg Branch, NIH, CRC, Bethesda, MD 20814 USA. Medarex Inc, Princeton, NJ USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC, Rm 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20814 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 51 TC 136 Z9 139 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2006 VL 29 IS 4 BP 455 EP 463 DI 10.1097/01.cji.0000208259.73167.58 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 056EX UT WOS:000238505300012 PM 16799341 ER PT J AU Newman, DJ Hill, RT AF Newman, David J. Hill, Russell T. TI New drugs from marine microbes: the tide is turning SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Industrial-Microbiology CY AUG 21-25, 2005 CL Chicago, IL SP Soc Ind Microbiol DE marine actinomycetes; microbial; metagenomics; Prochloron; secondary metabolites ID ASCIDIAN LISSOCLINUM-PATELLA; NEW-ZEALAND SPONGE; NATURAL-PRODUCTS; SALINISPORA-TROPICA; CYCLIC-PEPTIDES; BIOSYNTHESIS; ACTINOMYCETE; INHIBITOR; METABOLITES; SALINOSPORA AB This is a mini-review demonstrating that investigation of the genomics of marine microbes from all three domains has the potential to revolutionize the search for secondary metabolites originally thought to be the product of marine invertebrates. The basis for the review was a symposium at the 2005 Annual Meeting of the SIM covering some aspects of the potential for marine microbes to be the primary producers of such metabolites. The work reported at that symposium has been intearated into a fuller discussion of current published literature on the subject with examples drawn from bacteria, cyanophytes and fungi. C1 NCI Frederick, Nat Prod Branch, Dev Therapeut Program, Ft Detrick, MD 21702 USA. Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. RP Newman, DJ (reprint author), NCI Frederick, Nat Prod Branch, Dev Therapeut Program, POB B, Ft Detrick, MD 21702 USA. EM dn22a@nih.gov; hillr@umbi.umd.edu RI Jansen, Nils/G-1835-2011 NR 38 TC 72 Z9 77 U1 4 U2 19 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD JUL PY 2006 VL 33 IS 7 BP 539 EP 544 DI 10.1007/s10295-006-0115-2 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 069KC UT WOS:000239443800010 PM 16598493 ER PT J AU Tada, Y Riedl, E Lowenthal, MS Liotta, LA Briner, DM Crouch, EC Udey, MC AF Tada, Yayoi Riedl, Elisabeth Lowenthal, Mark S. Liotta, Lance A. Briner, David M. Crouch, Erika C. Udey, Mark C. TI Identification and characterization of endogenous langerin ligands in murine extracellular matrix SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID C-TYPE LECTIN; REGULATORY DENDRITIC CELLS; DC-SIGN; BIRBECK GRANULES; MOUSE LANGERIN/CD207; IMMUNE-SYSTEM; HUMAN-SKIN; T-CELLS; RECEPTOR; EXPRESSION AB Langerin is a C-type lectin that is expressed by Langerhans cells (LC) and related immune cells, and believed to play an important role in antigen recognition and uptake. To determine if Langerin has endogenous ligands, we generated S protein binding, bacterial recombinant, mouse soluble Langerin, and utilized it as a probe. Recombinant soluble Langerin did not bind to lymph node or spleen cells, or keratinocytes as assessed via flow cytometry. However, Langerin did bind to surfaces of primary skin fibroblasts and NIH3T3 cells. "Ligand blotting'' of fibroblast membrane-enriched fractions with Langerin revealed reproducible binding to 140 and 240 kDa proteins resolved in reduced denaturing gels. Characterization of these proteins using mass spectrometry suggested types I and III procollagen and fibronectin as candidate ligands. Langerin bound to type I procollagen that was immunoprecipitated from fibroblast lysates, but did not bind to fibronectin that was immunoprecipitated from fibroblast-conditioned media or mouse plasma fibronectin. These results indicate that Langerin selectively interacts with at least one ligand in extracellular matrix (type I procollagen). Langerin may have an unanticipated role in cell-matrix interactions that modulate LC development, localization, or function. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MA USA. NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MA USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N238, Bethesda, MD 20892 USA. EM udey@helix.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL-29594, HL-44015] NR 48 TC 9 Z9 9 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 JUL PY 2006 VL 126 IS 7 BP 1549 EP 1558 DI 10.1038/sj.jid.5700283 PG 10 WC Dermatology SC Dermatology GA 062UC UT WOS:000238969100020 PM 16557233 ER PT J AU Kostka, SL Knop, J Konur, A Udey, MC von Stebut, E AF Kostka, Susanna Lopez Knop, Juergen Konur, Abdo Udey, Mark C. von Stebut, Esther TI Distinct roles for IL-1 receptor type I signaling in early versus established Leishmania major infections SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID T-CELL-ACTIVATION; DENDRITIC CELLS; IFN-GAMMA; CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSES; SUSCEPTIBLE MICE; INTERLEUKIN-1; RESISTANT; MODEL; VITRO AB IL-1 alpha/beta released by infected dendritic cells (DC) plays a critical role in the development of protective immunity against Leishmania major. Previous studies demonstrated that treatment of susceptible BALB/c mice with IL-alpha a during T-cell priming (days 1-3 post-infection) induced T helper (Th) 1-mediated protection. In contrast, we now demonstrate that prolonged treatment with IL-1 alpha (for 3 weeks) worsened disease outcome. To characterize the receptor involved, L. major infections in IL-1 receptor type I (IL-1RI) knockout mice were studied. In C57BL/6 IL-1RI(-/-) mice, the IL-1 alpha-mediated protective effect was abrogated. The course of high-dose infection (2 x 10(5) parasites) in IL-1RI(-/-) mice was not different from controls. Surprisingly, in low-dose infections (10(3) parasites), IL-1RI(-/-) mice developed similar to 50% smaller lesions compared to wild types, decreased parasite loads and increased IFN gamma/IL-4 ratios. Interestingly, naive Th0 and Th2, but not Th1, cells expressed IL-1RI ex vivo. We conclude that IL-1RI mediates the effect of IL-1 alpha in leishmaniasis in C57BL/6 mice. In addition, IL-1 appears to play distinct roles in Th education and maintenance. In early phases of physiologically relevant, low-dose L. major infections, IL-1 facilitates Th1 development from Th0 cells, whereas later on IL-1RI signaling promotes Th2 expansion and worsens disease outcome. Effects of IL-1 on disease outcome may be related to levels of IL-1RI on Th subpopulations. C1 Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany. Univ Mainz, Dept Internal Med 3, D-55131 Mainz, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP von Stebut, E (reprint author), Univ Mainz, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany. EM vonstebu@mail.uni-mainz.de FU Intramural NIH HHS NR 40 TC 26 Z9 26 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2006 VL 126 IS 7 BP 1582 EP 1589 DI 10.1038/sj.jid.5700309 PG 8 WC Dermatology SC Dermatology GA 062UC UT WOS:000238969100023 PM 16645594 ER PT J AU Wolf, R Voscopoulos, CJ FitzGerald, PC Goldsmith, P Cataisson, C Gunsior, M Walz, M Ruzicka, T Yuspa, SH AF Wolf, Ronald Voscopoulos, Christopher J. FitzGerald, Peter C. Goldsmith, Paul Cataisson, Christophe Gunsior, Michele Walz, Markus Ruzicka, Thomas Yuspa, Stuart H. TI The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID KINASE-C-ALPHA; MULTIPLE SEQUENCE ALIGNMENT; KERATINOCYTE DIFFERENTIATION; BINDING PROTEINS; CALCIUM; SKIN; PSORIASIN; MARKERS; CELLS; INFLAMMATION AB The calcium-binding proteins of the human S100A7/A15 (hS100A7/A15) subfamily are differentially expressed in normal and pathological epidermis. The hS100A7 (psoriasin) and S100A15 reside in a chromosomal cluster of highly similar paralogs. To exploit the power of mouse models for determining functions of gene products, the corresponding S100A7/A15 ortholog was cloned and examined in murine skin. The single mouse S100A15 (mS100A15) gene encodes a protein of 104 amino acids with a predicted molecular weight of 12,870 Da and two EF-hand calcium binding sites. Using gene-specific primers and specific antibodies, expression of mS100A15 in both skin and isolated keratinocytes is confined to differentiating granular and cornified epidermal cells. Immunoblotting of epidermal extracts revealed a series of high molecular weight bands that are also recognized by an antibody for transglutaminase-mediated protein crosslinks. mS100A15 expression is upregulated in cultured keratinocytes induced to differentiate by calcium or phorbol esters. Maximal induction occurs concordantly with expression of late differentiation markers. Induction is enhanced in keratinocytes overexpressing protein kinase C alpha and is dependent on activator protein-1 transcription factors. The regulation, expression pattern and crosslinking of mS100A15 are consistent with the characteristics of the human orthologs, providing a valid surrogate model to study changes in these proteins associated with cutaneous pathologies. C1 NCI, Lab Cellular Carcingenesis & Tumor Promot, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Dermatol, D-4000 Dusseldorf, Germany. RP Yuspa, SH (reprint author), NCI, Lab Cellular Carcingenesis & Tumor Promot, Ctr Canc Res, NIH, 37 Convent Dr,MSC-4255,Bldg 37,Room 4068A, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU Intramural NIH HHS NR 41 TC 22 Z9 24 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 JUL PY 2006 VL 126 IS 7 BP 1600 EP 1608 DI 10.1038/sj.jid.5700210 PG 9 WC Dermatology SC Dermatology GA 062UC UT WOS:000238969100025 PM 16528363 ER PT J AU Djalilian, A McGaughey, D Patel, S Seo, E Yang, C Cheng, J Tomic, M Sinha, S Ishida-Yamamoto, A Segre, J AF Djalilian, A. McGaughey, D. Patel, S. Seo, E. Yang, C. Cheng, J. Tomic, M. Sinha, S. Ishida-Yamamoto, A. Segre, J. TI Connexin 26 regulates epidermal barrier, wound remodeling and promotes psoriasiform response SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NHGRI, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2006 VL 126 IS 7 MA 12 BP 1677 EP 1677 PG 1 WC Dermatology SC Dermatology GA 062UC UT WOS:000238969100074 ER PT J AU Rosenberg, HF Guyre, P Weaver, L AF Rosenberg, Helene F. Guyre, Paul Weaver, Lehn TI Interview with Dr. Paul Guyre and Mr. Lehn Weaver regarding pivotal advance: Activation of cell surface toll-like receptors causes shedding of the hemoglobin scavenger receptor CD163 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID EXPRESSION 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 7 TC 0 Z9 0 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 JUL PY 2006 VL 80 IS 1 BP 24 EP 25 DI 10.1189/jlb.1306756 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MD UT WOS:000243015500003 ER PT J AU Ui, I Okajo, A Endo, K Utsumi, H Matsumoto, K AF Ui, I Okajo, A Endo, K Utsumi, H Matsumoto, K TI Importance of volume limitation for tissue redox status measurements using nitroxyl contrast agents: A comparison of X-band EPR bile flow monitoring (BFM) method and 300 MHz in vivo EPR measurement SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE nitroxyl radical; tissue redox status; contrast agent; electron paramagnetic resonance imaging; magnetic resonance imaging ID ELECTRON-PARAMAGNETIC-RESONANCE; RAT-LIVER; SPIN-RESONANCE; DEFICIENT RAT; WHOLE MICE; PHARMACOKINETIC ANALYSIS; SELENIUM-DEFICIENT; RADICAL REDUCTION; ESR SPECTROSCOPY; MURINE TUMOR AB Methods proposed for in vivo redox status estimation, X-band (9.4 GHz) electron paramagnetic resonance (EPR) bile flow monitoring (BFM) and 300 MHz in vivo EPR measurement, were compared. The spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) was utilized for both methods, due to its suitable lipophilicity. EPR signal decay of a nitroxyl spin probe in the bile flow and in the liver region (upper abdomen) of several rat groups with different selenium status were measured by both the BFM and the in vivo EPR method, respectively. The nitroxyl radical clearance measured with in vivo EPR method may be affected not only by the redox status in the liver but also by information from other tissues in the measured region of the rat. On the other hand, the time course of nitroxyl radical level in the bile flow of rats was found to be a reliable index of redox status. Measurement site and/or volume limitation, which was achieved by the BFM method in this paper, is quite important in estimating reasonable EPR signal decay information as an index of tissue/organ redox status. (c) 2006 Elsevier Inc. All rights reserved. C1 Showa Pharmaceut Univ, Dept Phys Chem, Machida, Tokyo 1948543, Japan. Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Biofunct Sci, Fukuoka 8128582, Japan. NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Endo, K (reprint author), Showa Pharmaceut Univ, Dept Phys Chem, Machida, Tokyo 1948543, Japan. EM kazutoyo@ac.shoyaku.ac.jp NR 35 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 2006 VL 181 IS 1 BP 107 EP 112 DI 10.1016/j.jmr.2006.03.018 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 056TM UT WOS:000238548000011 PM 16632393 ER PT J AU Varga, R Avenarius, MR Kelley, PM Keats, BJ Berlin, CI Hood, LJ Morlet, TG Brashears, SM Starr, A Cohn, ES Smith, RJH Kimberling, WJ AF Varga, R Avenarius, MR Kelley, PM Keats, BJ Berlin, CI Hood, LJ Morlet, TG Brashears, SM Starr, A Cohn, ES Smith, RJH Kimberling, WJ TI OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID COCHLEAR IMPLANTATION; OTOACOUSTIC EMISSIONS; RECESSIVE DEAFNESS; FER-1-LIKE PROTEIN; ENCODING OTOFERLIN; MEMBRANE REPAIR; DOMAIN; DFNB9; FORM; DYSFERLIN AB Introduction: The majority of hearing loss in children can be accounted for by genetic causes. Nonsyndromic hearing loss accounts for 80% of genetic hearing loss in children, with mutations in DFNB1/GJB2 being by far the most common cause. Among the second tier genetic causes of hearing loss in children are mutations in the DFNB9/OTOF gene. Methods: In total, 65 recessive non-syndromic hearing loss families were screened by genotyping for association with the DFNB9/OTOF gene. Families with genotypes consistent with linkage or uninformative for linkage to this gene region were further screened for mutations in the 48 known coding exons of otoferlin. Results: Eight OTOF pathological variants were discovered in six families. Of these, Q829X was found in two families. We also noted 23 other coding variant, believed to have no pathology. A previously published missense allele I515T was found in the heterozygous state in an individual who was observed to be temperature sensitive for the auditory neuropathy phenotype. Conclusions: Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy. C1 BTNRH, Ctr Hereditary Commun Disorders, Omaha, NE 68131 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Iowa Hosp & Clin, Dept Otolaryngol, Mol Otolaryngol Res Lab, Iowa City, IA 52242 USA. LSU, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. LSU, Hlth Sci Ctr, Dept Otorhinolaryngol, New Orleans, LA USA. Univ Calif Irvine, Dept Neurol, Irvine, CA USA. Vanderbilt Univ, Med Ctr, Vanderbilt Bill Wilkerson Ctr, Dept Speech & Hearing Sci, Nashville, TN USA. AI DuPont Hosp Children, Auditory Physiol & Psychoacoust Lab, Wilmington, DE USA. AI DuPont Hosp Children, Audiol Clin, Wilmington, DE USA. RP Kelley, PM (reprint author), BTNRH, Dept Genet, 555 N 30th St, Omaha, NE 68131 USA. EM kelley@boystown.org FU NIDCD NIH HHS [2P01DC0813-07, 5P60DC00982, R01 DC000813, R01-DC02618, R01-DC02842] NR 39 TC 66 Z9 75 U1 1 U2 3 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 JUL PY 2006 VL 43 IS 7 BP 576 EP 581 DI 10.1136/jmg.2005.038612 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 059DP UT WOS:000238713800006 PM 16371502 ER PT J AU Cho, EH Lockett, SJ AF Cho, E. H. Lockett, S. J. TI Calibration and standardization of the emission light path of confocal microscopes SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE calibration; light-emitting diode; microscope standardization; optical microscope; photon counting; signal-to-noise ratio ID RESONANCE ENERGY-TRANSFER; FLUORESCENCE MICROSCOPY; SYSTEM PERFORMANCE; SINGLE-MOLECULE; PROTEINS; CELLS; COLOCALIZATION; DYNAMICS; RECOVERY; IMAGES AB Recently, there has been a large expansion in the usage of optical microscopes for obtaining quantitative information from biological samples in order to determine fundamental biological information such as molecular kinetics and interaction, and heterogeneity within cell populations. Consequently, we built a highly stable, uniform, isotropically emitting and convenient-to-use light source, and designed image analysis procedures for calibrating the emission light path of optical microscopes. We used the source and procedures to analyse the quantitative imaging properties of a widely used model of laser scanning confocal microscope. Results showed that the overall performance was as high as could be expected given the inherent limitations of the optical components and photomultiplier tubes. We observed that the photon detection efficiency did not vary with photomultiplier tube gain and that the highest dynamic range was achieved with relatively low gain and 12-bit digitization. Practical applications of the light source for checking the transmission of optical components in the emission light path are presented. C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Image Anal Lab, Ft Detrick, MD 21702 USA. RP Cho, EH (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Image Anal Lab, POB B, Ft Detrick, MD 21702 USA. EM slockett@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 32 TC 10 Z9 10 U1 2 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD JUL PY 2006 VL 223 BP 15 EP 25 DI 10.1111/j.1365-2818.2006.01598.x PN 1 PG 11 WC Microscopy SC Microscopy GA 061RK UT WOS:000238889900003 PM 16872427 ER PT J AU Kaye, FJ AF Kaye, Frederic J. TI A unifying proposal for MECT1-MAML2 tumorigenesis SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Letter ID OF-THE-LITERATURE; MUCOEPIDERMOID CARCINOMA; GLAND TUMORS; GENE FUSION; CLASSIFICATION; SKIN C1 NCI, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD 20892 USA. RP Kaye, FJ (reprint author), NCI, Bethesda, MD 20892 USA. RI kaye, frederic/E-2437-2011 NR 17 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2006 VL 8 IS 3 BP 395 EP 396 PG 2 WC Pathology SC Pathology GA 064RM UT WOS:000239106800018 ER PT J AU Shen, J AF Shen J TI In vivo evidence for a correlation between increased GABA level and reduced glutamate-glutamine cycling rate SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 7th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY JUL 02-05, 2006 CL Singapore, SINGAPORE SP Asia Pacific Soc Neurochem C1 NIMH, Intramural Res Program, 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2006 VL 98 SU 1 BP 59 EP 59 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 066QQ UT WOS:000239245600131 ER PT J AU LopezJimenez, ND Cavenagh, MM Sainz, E Cruz-Ithier, MA Battey, JF Sullivan, SL AF LopezJimenez, ND Cavenagh, MM Sainz, E Cruz-Ithier, MA Battey, JF Sullivan, SL TI Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE chemosensory signal transduction; polycystic kidney disease; polycystin; salty taste; sour taste; TRP ion channel ID POLYCYSTIC KIDNEY-DISEASE; SOUR TASTE; CATION CHANNEL; UMAMI TASTE; SWEET TASTE; MAMMALIAN SWEET; GENE ENCODES; BITTER TASTE; PROTEIN; IDENTIFICATION AB Taste receptors cells are responsible for detecting a wide variety of chemical stimuli. Several molecules including both G protein coupled receptors and ion channels have been shown to be involved in the detection and transduction of tastants. We report on the expression of two members of the transient receptor potential (TRP) family of ion channels, PKD1L3 and PKD2L1, in taste receptor cells. Both of these channels belong to the larger polycystic kidney disease (PKD or TRPP) subfamily of TRP channels, members of which have been demonstrated to be non-selective cation channels and permeable to both Na+ and Ca2+. Pkd1l3 and Pkd2l1 are co-expressed in a select subset of taste receptor cells and therefore may, like other PKD channels, function as a heteromer. We found the taste receptor cells expressing Pkd1l3 and Pkd2l1 to be distinct from those that express components of sweet, bitter and umami signal transduction pathways. These results provide the first evidence for a role of TRPP channels in taste receptor cell function. C1 Natl Inst Deafness & Other Commun Disorder, Lab Mol Biol, NIH, Rockville, MD 20850 USA. RP Sullivan, SL (reprint author), Natl Inst Deafness & Other Commun Disorder, Lab Mol Biol, NIH, 5 Res Court, Rockville, MD 20850 USA. EM sullivas@nidcd.nih.gov FU Intramural NIH HHS NR 68 TC 93 Z9 100 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2006 VL 98 IS 1 BP 68 EP 77 DI 10.1111/j.1471-4159.2006.03842.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 052TD UT WOS:000238255900007 PM 16805797 ER PT J AU Ravni, A Bourgault, S Lebon, A Chan, P Galas, L Fournier, A Vaudry, H Gonzalez, B Eiden, LE Vaudry, D AF Ravni, A Bourgault, S Lebon, A Chan, P Galas, L Fournier, A Vaudry, H Gonzalez, B Eiden, LE Vaudry, D TI The neurotrophic effects of PACAP in PC12 cells: control by multiple transduction pathways SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE differentiation; microarray; nerve growth factor; pituitary adenylate cyclase-activating polypeptide; PC12 cells; transduction pathways ID NERVE GROWTH-FACTOR; CYCLASE-ACTIVATING POLYPEPTIDE; CEREBELLAR GRANULE CELLS; SIGNAL-REGULATED KINASE; VASOACTIVE-INTESTINAL-PEPTIDE; INDUCED NEURITE OUTGROWTH; IMMEDIATE-EARLY GENE; ADENYLATE-CYCLASE; MAP-KINASE; PHEOCHROMOCYTOMA CELLS AB Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are closely related members of the secretin superfamily of neuropeptides expressed in both the brain and peripheral nervous system, and they exhibit neurotrophic and neurodevelopmental effects in vivo. Like the index member of the Trk receptor ligand family, nerve growth factor (NGF), PACAP promotes the differentiation of PC12 cells, a well-established cell culture model, to investigate neuronal differentiation, survival and function. Stimulation of catecholamine secretion and enhanced neuropeptide biosynthesis are effects exerted by PACAP at the adrenomedullary synapse in vivo and on PC12 cells in vitro through stimulation of the specific PAC1 receptor. Induction of neuritogenesis, growth arrest, and promotion of cell survival are effects of PACAP that occur in developing cerebellar, hippocampal and cortical neurons, as well as in the more tractable PC12 cell model. Study of the mechanisms through which PACAP exerts its various effects on cell growth, morphology, gene expression and survival, i.e. its actions as a neurotrophin, in PC12 cells is the subject of this review. The study of neurotrophic signalling by PACAP in PC12 cells reveals that multiple independent pathways are coordinated in the PACAP response, some activated by classical and some by novel or combinatorial signalling mechanisms. C1 Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol, Mont St Aignan, France. Univ Quebec, Inst Natl Rech Sci, Inst Armand Frappier, Pointe Claire, PQ, Canada. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Vaudry, H (reprint author), Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol, Mont St Aignan, France. EM hubert.vaudry@Univ-rouen.fr RI galas, ludovic/A-2500-2014; Gonzalez, Bruno/E-6103-2016; OI Eiden, Lee/0000-0001-7524-944X; Vaudry, David/0000-0003-3567-7452 FU Intramural NIH HHS NR 102 TC 81 Z9 82 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2006 VL 98 IS 2 BP 321 EP 329 DI 10.1111/J.1471-4159.2006.03884.X PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 055YJ UT WOS:000238487000001 PM 16805827 ER PT J AU Solinas, M Justinova, Z Goldberg, SR Tanda, G AF Solinas, M Justinova, Z Goldberg, SR Tanda, G TI Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE anandamide; dopamine release; endogenous cannabinoids; FAAH enzyme; nucleus accumbens shell; reward ID RECEPTOR KNOCKOUT MICE; CANNABINOID RECEPTOR; VANILLOID RECEPTORS; BRAIN REWARD; PHARMACOLOGICAL-ACTIVITY; VENTRAL TEGMENTUM; SUBSTANTIA-NIGRA; MOUSE-BRAIN; SR 141716A; ANTAGONIST AB Although endogenous cannabinoid systems have been implicated in the modulation of the rewarding effects of abused drugs and food, little is known about the direct effects of endogenous ligands for cannabinoid receptors on brain reward processes. Here we show for the first time that the intravenous administration of anandamide, an endogenous ligand for cannabinoid receptors, and its longer-lasting synthetic analog methanandamide, increase the extracellular dopamine levels in the nucleus accumbens shell of awake, freely moving rats, an effect characteristic of most drugs abused by humans. Anandamide produced two distinctly different effects on dopamine levels: (1) a rapid, transient increase that was blocked by the cannabinoid CB1 receptor antagonist rimonabant, but not by the vanilloid VR1 receptor antagonist capsazepine, and was magnified and prolonged by the fatty acid amide hydrolase (FAAH) enzyme inhibitor, URB597; (2) a smaller delayed and long-lasting increase, not sensitive to CB1, VR1 or FAAH blockade. Both effects were blocked by infusing either tetrodotoxin (TTX, 1 mu m) or calcium-free Ringer's solution through the microdialysis probe, demonstrating that they were dependent on the physiologic activation of dopaminergic neurotransmission. Thus, these results indicate that anandamide, through the activation of the mesolimbic dopaminergic system, participates in the signaling of brain reward processes. C1 NIDA, Psychobiol Sect, Medicat Discovery Res Branch, IRP,NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, IRP,NIH,DHHS, Baltimore, MD 21224 USA. Univ Poitiers, CNRS 6187, Lab Biol & Physiol Cellulaire, Poitiers, France. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. RP Tanda, G (reprint author), NIDA, Psychobiol Sect, Medicat Discovery Res Branch, IRP,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gtanda@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011; Solinas, Marcello/M-3500-2016 OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484; Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS NR 69 TC 100 Z9 103 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2006 VL 98 IS 2 BP 408 EP 419 DI 10.1111/j.1471-4159.2006.03880.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 055YJ UT WOS:000238487000010 PM 16805835 ER PT J AU Kretschmannova, K Gonzalez-Iglesias, AE Tomic, M Stojilkovic, SS AF Kretschmannova, K Gonzalez-Iglesias, AE Tomic, M Stojilkovic, SS TI Dependence of hyperpolarisation-activated cyclic nucleotide-gated channel activity on basal cyclic adenosine monophosphate production in spontaneously firing GH(3) cells SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE GH(3) cells; pacemaking; l(h) current; prolactin; ZD7288 ID CURRENT I-H; ANTERIOR-PITUITARY-CELLS; CARDIAC-PACEMAKER CHANNELS; RABBIT SINOATRIAL NODE; CATION CURRENT; CALCIUM OSCILLATIONS; HORMONE-SECRETION; SODIUM CURRENT; FUNNY CURRENT; ION CHANNELS AB The hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels play a distinct role in the control of membrane excitability in spontaneously active cardiac and neuronal cells. Here, we studied the expression and role of HCN channels in pacemaking activity, Ca2+ signalling, and prolactin secretion in GH(3) immortalised pituitary cells. Reverse transcriptase-polymerase chain reaction analysis revealed the presence of mRNA transcripts for HCN2, HCN3 and HCN4 subunits in these cells. A hyperpolarisation of the membrane potential below - 60 mV elicited a slowly activating voltage-dependent inward current (I-h) in the majority of tested cells, with a half-maximal activation voltage of -89.9 +/- 4.2 mV and with a time constant of 1.4 +/- 0.2 s at -120 mV. The bath application of 1 mM Cs+, a commonly used inorganic blocker of I-h, and 100 mu M ZD7288, a specific organic blocker of I-h, inhibited I-h by 90 +/- 4.1% and 84.3 +/- 1.8%, respectively. Receptor- and nonreceptor-mediated activation of adenylyl and soluble guanylyl cyclase and the addition of a membrane permeable cyclic adenosine monophosphate (cAMP) analogue, 8-Br-cAMP, did not affect I-h. Inhibition of basal adenylyl cyclase activity, but not basal soluble guanylyl cyclase activity, led to a reduction in the peak amplitude and a leftward shift in the activation curve of I-h by 23.7 mV. The inhibition of the current was reversed by stimulation of adenylyl cyclase with forskolin and by the addition of 8-Br-cAMP, but not 8-Br-cGMP. Application of Cs+ had no significant effect on the resting membrane potential or electrical activity, whereas ZD7288 exhibited complex and I-h-independent effects on spontaneous electrical activity, Ca2+ signalling, and prolactin release. These results indicate that HCN channels in GH(3) cells are under tonic activation by basal level of cAMP and are not critical for spontaneous firing of action potentials. C1 NICHD, Sect Cellular Signalling, ERRB, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Cellular Signalling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Kretschmannova, K (reprint author), NICHD, Sect Cellular Signalling, ERRB, NIH, Bldg 49,Room 6C-20,49 Convent Dr, Bethesda, MD 20892 USA. EM kretschk@mail.nih.gov RI Tomic, Melanija/C-3371-2016 NR 53 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUL PY 2006 VL 18 IS 7 BP 484 EP 493 DI 10.1111/j.1365-2826.01438.x PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 050CL UT WOS:000238065000002 PM 16774497 ER PT J AU Cheng, YZ Gu, J Nash, HA AF Cheng, Yuzhong Gu, Joy Nash, Howard A. TI Interaction of the Drosophila trp channel with a peptide encoded by the inaF locus SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 NIMH, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PD JUL-DEC PY 2006 VL 20 IS 3-4 BP 101 EP 102 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 123QD UT WOS:000243309500045 ER PT J AU Lear, BC Allada, R Nash, HA Scott, RL AF Lear, Bridget C. Allada, Ravi Nash, Howard A. Scott, Robert L. TI A novel regulator of an unusual ion channel SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PD JUL-DEC PY 2006 VL 20 IS 3-4 BP 158 EP 159 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 123QD UT WOS:000243309500120 ER PT J AU Luan, HJ Wan, KH Peabody, NC White, BH AF Luan, Haojiang Wan, Kevin Ho Peabody, Nathan C. White, Benjamin H. TI Dissection of a neuronal network required for wing expansion using a novel split Gal4 system SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PD JUL-DEC PY 2006 VL 20 IS 3-4 BP 168 EP 169 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 123QD UT WOS:000243309500133 ER PT J AU Scott, RL Nash, HA Allada, R Lear, BC AF Scott, Robert L. Nash, Howard A. Allada, Ravi Lear, Bridget C. TI Functional anatomy of an unusual ion channel SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PD JUL-DEC PY 2006 VL 20 IS 3-4 BP 216 EP 217 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 123QD UT WOS:000243309500191 ER PT J AU Tanaka, N Ito, K Stopfer, M AF Tanaka, Nobuaki Ito, Kei Stopfer, Mark TI Intracellular recording from antennal lobe neurons SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD 20892 USA. Univ Tokyo, Int Mol & Celluar Biosci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PD JUL-DEC PY 2006 VL 20 IS 3-4 BP 235 EP 236 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 123QD UT WOS:000243309500215 ER PT J AU Vreede, AP Peabody, NC Zelensky, PK White, BH AF Vreede, Andrew P. Peabody, Nathan C. Zelensky, Paul K. White, Benjamin H. TI Acute enhancement of excitability in the CCAP neuronal network prior to eclosion using the TRPM8 channel blocks post-eclosion wing expansion SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PD JUL-DEC PY 2006 VL 20 IS 3-4 BP 251 EP 252 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 123QD UT WOS:000243309500235 ER PT J AU Wang, CH Chou, YK Rich, CM Link, JM Afentoulis, ME van Noort, JM Wawrousek, EF Offner, H Vandenbark, AA AF Wang, Chunhe Chou, Yuan K. Rich, Cathleen M. Link, Jason M. Afentoulis, Michael E. van Noort, Johannes M. Wawrousek, Eric F. Offner, Halina Vandenbark, Arthur A. TI alpha B-crystallin-reactive T cells from knockout mice are not encephalitogenic SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE tolerance; EAE/MS; T cells; knockout mice ID HEAT-SHOCK PROTEINS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; A-CRYSTALLIN; CANDIDATE AUTOANTIGEN; PROTECTIVE ACTIVITY; INDUCED APOPTOSIS; STRESS-PROTEINS; IN-VITRO; EXPRESSION AB Alpha B-crystallin (sigma B) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for sigma B protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained sigma B-knockout (sigma B-KO) mice in H-2(b) background that lack immune tolerance to sigma B protein, and thus are capable of developing sigma B-specific T cells that could be tested for encephalitogenic activity after transfer into sigma B-expressing wild type (WT) mice. We found that T cell lines from spleens of sigma B protein-immunized sigma B-KO mice proliferated strongly to sigma B protein itself, and the majority of T cells were CD4(+) and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such sigma B-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, sigma B-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of sigma B message in the CNS at the time of transfer. These results suggest that sigma B-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of sigma B. (c) 2006 Elsevier B.V. All rights reserved. C1 Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. TNO Prevent & Hlth, Div Immunol & Infect Dis, NL-2301 CE Leiden, Netherlands. NEI, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Wang, CH (reprint author), Vet Affairs Med Ctr, Portland, OR 97239 USA. EM wangch@ohsu.edu RI Wawrousek, Eric/A-4547-2008; OI Link, Jason/0000-0002-6892-0431; van Noort, Johannes/0000-0002-9060-5921 FU NIAID NIH HHS [AI43960]; NINDS NIH HHS [NS23444, NS41965, NS49210, NS47661, NS46877, NS45445] NR 37 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 2006 VL 176 IS 1-2 BP 51 EP 62 DI 10.1016/j.jneuroim.2006.04.010 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 081NC UT WOS:000240323300007 PM 16844233 ER PT J AU Johnson-Nauroth, JM Graber, J Yao, K Jacobson, S Calabresi, PA AF Johnson-Nauroth, Julie M. Graber, Jerome Yao, Karen Jacobson, Steve Calabresi, Peter A. TI Memory lineage relationships in HTLV-1-specific CD8+ cytotoxic T cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE cytotoxic T cells; memory; viral infection ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; KAPPA-B SITE; HTLV-I; NEUROLOGIC DISEASE; PROVIRAL LOAD; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; CHAIN EXPRESSION AB Cytotoxic memory T cells play a critical role in combating viral infections; however, in some diseases they may contribute to tissue damage. In HAM/TSP, HTLV-1 Tax 11-19+ cells proliferate spontaneously in vitro and can be tracked using the Tax 11-19 MHC Class I tetramer. Immediately ex vivo, these cells were a mix of CD45RA(-)/CCR7(-) T-EM and CD45RA(+)/CCR7(-) T-Diff memory CTL. The subsequent proliferating Tax 11-19 tetramer+ population expressed low levels of IL-7R alpha failed to respond to IL-7 and IL-15, and did not develop a T-CM phenotype. Thus, chronic exposure to viral antigen may result in a sustained pool of T-EM cells that home to the CNS and mediate the spinal cord pathology seen in this disease. (c) 2006 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Johns Hopkins Hosp, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. NINDS, NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Calabresi, PA (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Dept Neurol, Sch Med, 600 N Wolfe St,Pathol Bldg 627, Baltimore, MD 21287 USA. EM pcalabr1@jhmi.edu FU Intramural NIH HHS [Z01 NS002817-18, Z01 NS002817-19, Z01 NS003040-01]; NINDS NIH HHS [NS041435, R01 NS041435, R37 NS041435] NR 47 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 2006 VL 176 IS 1-2 BP 115 EP 124 DI 10.1016/j.jneuroim.2006.03.013 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 081NC UT WOS:000240323300013 PM 16740321 ER PT J AU Colucci, M Moleres, FJ Xie, ZL Ray-Chaudhury, A Gutti, S Butefisch, CM Cervenakova, L Wang, W Goldfarb, LG Kong, QZ Ghetti, B Chen, SG Gambetti, P AF Colucci, Monica Moleres, Francisco J. Xie, Zhi-Liang Ray-Chaudhury, Abhik Gutti, Sujata Butefisch, Cathrin M. Cervenakova, Larisa Wang, Wen Goldfarb, Lev G. Kong, Qingzhong Ghetti, Bernardino Chen, Shu G. Gambetti, Pierlulgi TI Gerstmann-Straussler-Scheinker: A new phenotype with 'curly' PrP deposits SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE amyloid; Gerstmann-Straussler-Scheinker; neurofibrillary tangles; prion ID CREUTZFELDT-JAKOB-DISEASE; FATAL FAMILIAL INSOMNIA; ABNORMAL PRION PROTEIN; PRNP H187R MUTATION; MONOCLONAL-ANTIBODY; DNA POLYMORPHISM; TRUNCATED FORMS; ENCEPHALOPATHY; IDENTIFICATION; FRAGMENTS AB Gerstmann-Straussler-Scheinker (GSS) is a hereditary prion disease typically associated with prion protein (PrP)-containing plaques. The protease-resistant, scrapie PrP (PrPSc) is represented by internal fragments, whereas the C-terminal fragments associated with the other prion diseases are generally underrepresented. Different histopathologic and PrPSc features associated with at least 13 PrP gene (PRNP) mutations have been described in GSS. We report the histopathology and PrP characteristics in a father and son carrying a mutation at PRNP codon 187 that substitutes histidine (H) with arginine (R) and is coupled with valine (V) at position 129 (H187R129V). The PrP plaques were present in both cases but with different structure and topography and minimal spongiform degeneration. A distinctive, "curly" PrP immunostaining was prominent in one case. The protease-resistant PrPSc differed in amount in the 2 cases, possibly depending on whether plaques or the curly immunostain was present. Two protease-resistant PrP fragments of 14 kDa and 7 kDa with, in at least one case, N-terminus between residues 90-99 and 82-90, respectively, codistributed with the plaques, whereas only very small amounts of the PK-resistant PrP were present in the curly staining regions. PK-resistant PrP recovered from the plaque and curly staining regions appeared to be full length. C1 Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Bloomington, IN 47405 USA. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Bloomington, IN 47405 USA. NINDS, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Neurol Therapy Ctr Dusseldorf, Dusseldorf, Germany. Pikeville Neurol Clin & Diag Ctr, Pikeville, KY USA. Ohio State Univ, Div Neuropathol, Dept Pathol, Columbus, OH 43210 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Univ Genoa, Dept Neurol Sci & Vis, I-16126 Genoa, Italy. RP Gambetti, P (reprint author), Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd,Room 419, Cleveland, OH 44106 USA. EM pxg13@case.edu RI Chen, Shu/O-4750-2014 OI Chen, Shu/0000-0001-7180-3001 FU NIA NIH HHS [AG08012, AG10133, AG14359]; PHS HHS [CCU 515004] NR 30 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 2006 VL 65 IS 7 BP 642 EP 651 DI 10.1097/01.jnen.0000228198.81797.4d PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 100TQ UT WOS:000241692200002 PM 16825951 ER PT J AU Zhu, PJ Lovinger, DM AF Zhu, PJ Lovinger, DM TI Ethanol potentiates GABAergic synaptic transmission in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GABA(A) RECEPTOR-ACTIVITY; RAT HIPPOCAMPUS; DEPENDENT RATS; PROTEIN-KINASE; IN-VITRO; NEURONS; FEAR; MODULATION; ALCOHOL; RESPONSES AB Interactions between ethanol and synaptic transmission mediated by gamma-amino-N-butyric acid (GABA) have been suggested to contribute to alcohol intoxication. Ethanol effects on postsynaptic GABA(A) receptors have been the major focus of this line of research. There is increasing evidence that ethanol potentiation of GABAergic transmission involves increased GABA release from presynaptic terminals. In the present study, a mechanically isolated neuron/bouton preparation from the basolateral amygdala was used to examine the effects of ethanol on spontaneous GABAergic synaptic currents elicited by GABA release from the presynaptic terminals. We found that ethanol application produced a rapid increase in the frequency of spontaneous GABAergic synaptic currents. An acute tolerance to ethanol was also observed, and this tolerance involved GABA(B) receptor activation. The ethanol-induced potentiation did not involve alterations in the function of postsynaptic GABA(A) receptors and was independent of presynaptic action potential firing. These findings indicate that ethanol potentiates GABA release, most likely via a direct action on presynaptic boutons. C1 NIAAA, NIH, Lab Integrat Neurosci, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, NIH, Lab Integrat Neurosci, 5625 Fisheries Ln Rm TS-28, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov FU Intramural NIH HHS NR 47 TC 45 Z9 47 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2006 VL 96 IS 1 BP 433 EP 441 DI 10.1152/jn.01380.2005 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 052VQ UT WOS:000238262400037 PM 16624993 ER PT J AU Israelsson, C Lewen, A Kylberg, A Usoskin, D Althini, S Lindeberg, J Deng, CX Fukuda, T Wang, Y Kaartinen, V Mishina, Y Hillered, L Ebendal, T AF Israelsson, Charlotte Lewen, Anders Kylberg, Annika Usoskin, Dmitry Althini, Susanna Lindeberg, Jonas Deng, Chu-Xia Fukuda, Tomokazu Wang, Yun Kaartinen, Vesa Mishina, Yuji Hillered, Lars Ebendal, Ted TI Genetically modified bone morphogenetic protein signalling alters traumatic brain injury-induced gene expression responses in the adult mouse SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE TBI; activin receptor-1; Smad4; CaMKII-Cre; glial fibrillary acidic protein ID CENTRAL-NERVOUS-SYSTEM; SERINE/THREONINE KINASE RECEPTORS; MICROTUBULE-ASSOCIATED PROTEIN-2; MESSENGER-RNA; TISSUE INHIBITOR; DENDRITIC GROWTH; MICE; BMP; HIPPOCAMPUS; ISCHEMIA AB Three genetic mouse models were examined to define effects of bone morphogenetic protein (BMP) signalling on gene expression in normal and injured adult brain. CaMKII-Cre eliminated the BMP receptor Acvr1 (Alk2) and the common TGF beta superfamily signal mediator Smad4 or activated a constitutively active Acvr1 in postnatal forebrain neurons. All mutants followed mendelian ratios, with no overt phenotypic changes. In situ hybridization demonstrated normal patterns of the dendritic marker MAP2 (Mtap2) throughout cortex despite neuron-specific losses of Acvr1 or Smad4. However, strong up-regulation of Mtap2 transcript in these mice was found by quantitative RT-PCR (qRT-PCR), indicating that Mtap2 is normally suppressed by BMR Traumatic brain injury (TBI) resulted in increases of histone-associated DNA fragments in both control and Smad4-deficient cortex. Several cell-type-specific transcripts known to be involved in injury-related responses were measured by qRT-PCR. Gfap mRNA was strongly upregulated in controls as well as in the loss-of-BMP-signalling mutants. Notably, activated Acvr1 signalling gave significantly lower TBI-induced up-regulations of Gfap and Phox2a mRNA levels, indicating reductions in astroglial and neuronal reactions to injury. Strong impairment in injury-induced Timp1 transcript up-regulation was also seen in these mice. In contrast, osteopontin (Spp1) transcript levels in activated microglia were not reduced by Acvr1 signalling. Altogether, the data suggest that BMP signalling is dispensable in adult cortical neurons but that augmented BMP signalling affects molecular changes associated with neuronal lesions. (c) 2006 Wiley-Liss, Inc. C1 Uppsala Univ, Dept Neurosci, Biomed Ctr, SE-75123 Uppsala, Sweden. Univ Uppsala Hosp, Uppsala, Sweden. NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIDA, NIH, Neurol Protect & Regenerat Sect, Baltimore, MD 21224 USA. Univ So Calif, Childrens Hosp, Dev Biol Program, Los Angeles, CA 90027 USA. RP Ebendal, T (reprint author), Uppsala Univ, Dept Neurosci, Biomed Ctr, Box 587, SE-75123 Uppsala, Sweden. EM ted.ebendal@neuro.uu.se RI Lewen, Anders/A-5156-2013; deng, chuxia/N-6713-2016; OI Lewen, Anders/0000-0003-4925-1348; Kaartinen, Vesa/0000-0002-9432-510X FU NHLBI NIH HHS [HL074862]; NIDCR NIH HHS [DE013085] NR 51 TC 16 Z9 16 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL PY 2006 VL 84 IS 1 BP 47 EP 57 DI 10.1002/jnr.20856 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 061UD UT WOS:000238897400005 PM 16583403 ER PT J AU Petzold, A Keir, G Kerr, M Kay, A Kitchen, N Smith, M Thompson, EJ AF Petzold, Axel Keir, Geoffrey Kerr, Mary Kay, Andrew Kitchen, Neil Smith, Martin Thompson, Edward J. TI Early identification of secondary brain damage in subarachnoid hemorrhage: A role for glial fibrillary acidic protein SO JOURNAL OF NEUROTRAUMA LA English DT Article DE astrocytosis; biomarker; cell culture; cerebrospinal fiuid; GFAP; neuro-critical care; subarachnoid hemorrhage ID GOOD NEUROLOGICAL RECOVERY; NEURON-SPECIFIC ENOLASE; CEREBROSPINAL-FLUID; S-100 PROTEIN; PSYCHOSOCIAL OUTCOMES; SERUM S100B; ISCHEMIA; MANAGEMENT; MARKERS; INJURY AB Secondary ischaemic deficit adversely affects outcome in patients with subarachnoid hemorrhage (SAH). Astrocytes are vulnerable to ischemia, releasing glial fibrillary acidic protein (GFAP) when challenged. In this study, we followed nine patients with SAH who underwent extra-ventricular drainage for the management of secondary hydrocephalus. Cerebrospinal fluid (CSF) was collected daily for up to 14 days. CSF GFAP was quantified using a standard ELISA. In the patients, we found that the CSF GFAP values were pathologically elevated in 83/89 (93%) of the CSF samples. The levels were highest on day 1 (median = 47.64 ng/mL) and decreased to 11.19 ng/mL on day 3, leveling out at approximately 1 ng/mL after 10 days. In non-survivors, a secondary rise of GFAP levels became significant during the high-risk period for vasospasm, with median levels of 21.76 ng/mL compared to 2.62 ng/mL in the survivors (p = 0.037) on day 6. This study suggests that CSF GFAP levels are of prognostic value in SAH. Additionally, the difference in the slope of GFAP levels between survivors (rapid wash-out) and non-survivors (secondary peaks) may allow differentiation between primary brain injury from secondary brain damage due to delayed cerebral ischaemia. C1 UCL, Inst Neurol, Dept Neuroimmunol, London, England. Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. NINR, NIH, Bethesda, MD 20892 USA. Univ Hosp Birmingham, Queen Elizabeth Med Ctr, Dept Neurosurg, Queen Elizabeth Neurosci Ctr, Birmingham, W Midlands, England. RP Petzold, A (reprint author), UCL, Inst Neurol, Dept Neuroimmunol, London, England. EM a.petzold@ion.ucl.ac.uk RI Petzold, Axel/C-1090-2009; Smith, Martin/B-2616-2009 OI Petzold, Axel/0000-0002-0344-9749; FU NINR NIH HHS [R01NR0433] NR 27 TC 16 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2006 VL 23 IS 7 BP 1179 EP 1184 DI 10.1089/neu.2006.23.1179 PG 6 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 069UG UT WOS:000239473200012 PM 16866629 ER PT J AU Sander, WE Metzger, ME Morizono, K Bonifacino, A Penzak, SR Xie, YM Chen, ISY Bacon, J Sestrich, SG Szajek, LP Donahue, RE AF Sander, William E. Metzger, Mark E. Morizono, Kouki Bonifacino, Aylin Penzak, Scott R. Xie, Yi-Ming Chen, Irvin S. Y. Bacon, Jeffrey Sestrich, Stephen G. Szajek, Lawrence P. Donahue, Robert E. TI Noninvasive molecular imaging to detect transgene expression of lentiviral vector in nonhuman primates SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Br-76-FBAU; gene therapy; PET; nonhuman primates; molecular imaging ID POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE-EXPRESSION; IN-VIVO; LIVING ANIMALS; PET; REPLICATION; ANTIBODIES; THERAPY; BR-76; CELLS AB Noninvasive imaging of a reporter gene is a new and promising technique to quantify transgene expression after gene therapy. This study was performed to demonstrate visualization of lentiviral-marked cells by PET. Methods: We transduced nonhuman primate CD34(+) hematopoietic cells with a lentiviral vector expressing a PET reporter gene, the mutant viral herpes simplex virus type 1-thymidine kinase (HSV1-sr39tk) gene. 1-(2-Fluoro2-deoxy-beta-D-arabinofuranosyl)-Br-76-5-bromouracil (Br-76-FBAU) was used as the substrate for the viral tk enzyme. Upon phosphorylation, Br-76-FBAU was retained by cells and imaged by PET. The long half-life of Br-76, 16.2 h, permitted us to perform extended pharmacokinetic and imaging studies. Results: Br-76-FBAU was retained in vascular tissues of the animals with transplanted tk lentiviral vector-transcluced CD34(+) cells. Elimination of Br-76-FBAU was through renal and hepatic excretion. Conclusion: Noninvasive molecular imaging using PET will help us, in the future, to define the contribution and distribution of cells and their progeny to tissue repair and development. C1 NHLBI, Hematol Branch, Rockville, MD 20850 USA. Univ Calif Los Angeles, Sch Med, AIDS Inst, Los Angeles, CA USA. NIH, Ctr Clin, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, PET Imaging Sect, Bethesda, MD 20892 USA. RP Donahue, RE (reprint author), NHLBI, Hematol Branch, 5 Res Ct, Rockville, MD 20850 USA. EM donahuer@nhlbi.nih.gov FU Intramural NIH HHS NR 24 TC 14 Z9 14 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 JUL PY 2006 VL 47 IS 7 BP 1212 EP 1219 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061NM UT WOS:000238879300026 PM 16818958 ER PT J AU Lanza, E Hartman, TJ Albert, PS Shields, R Slattery, M Caan, B Paskett, E Iber, F Kikendall, JW Lance, P Daston, C Schatzkin, A AF Lanza, E Hartman, TJ Albert, PS Shields, R Slattery, M Caan, B Paskett, E Iber, F Kikendall, JW Lance, P Daston, C Schatzkin, A TI High dry bean intake and reduced risk of advanced colorectal adenoma recurrence among participants in the polyp prevention trial SO JOURNAL OF NUTRITION LA English DT Article DE dry beans; fruits and vegetables; colorectal cancer; colorectal adenoma; advanced colorectal adenoma ID DIETARY GLYCEMIC LOAD; COLON-CANCER; RECTAL-CANCER; PLANT FOODS; CARCINOMA SEQUENCE; RANDOMIZED-TRIAL; WOMENS HEALTH; UNITED-STATES; HIGH-FIBER; LOW-FAT AB Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial-based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18-0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial-based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence. C1 NCI, Ctr Canc Res, Lab Canc Prevent, Bethesda, MD 20892 USA. Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. Univ Utah, Salt Lake City, UT USA. Kaiser Informat Management Serv, Oakland, CA USA. Ohio State Canc Ctr, Columbus, OH USA. Vet Affairs Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Daston Commun, Chapel Hill, NC USA. NCI, Div Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Lanza, E (reprint author), NCI, Ctr Canc Res, Lab Canc Prevent, Bethesda, MD 20892 USA. EM el33t@nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 CN000151-17] NR 61 TC 43 Z9 44 U1 3 U2 11 PU AMER SOCIETY 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 JUL PY 2006 VL 136 IS 7 BP 1896 EP 1903 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 057VV UT WOS:000238624200024 PM 16772456 ER PT J AU Shorr, RI De Rekeneire, N Resnick, HE Yaffe, K Somes, GW Kanaya, AM Simonsick, EM Newman, AB Harris, TB AF Shorr, R. I. De Rekeneire, N. Resnick, H. E. Yaffe, K. Somes, G. W. Kanaya, A. M. Simonsick, E. M. Newman, A. B. Harris, T. B. TI Glycemia and cognitive function in older adults using glucose-lowering drugs SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article ID MINI-MENTAL-STATE; DEPENDENT DIABETES-MELLITUS; WORKING-MEMORY; ELDERLY HUMANS; INSULIN; HYPERGLYCEMIA; HYPOGLYCEMIA; ENHANCEMENT; PERFORMANCE; DEMENTIA AB Objectives: In experimental studies, both high and low levels of plasma glucose are associated with cognitive impairment. In populations, less is known about the relationship between glycemia and cognitive function, especially in persons using glucose-lowering drugs. Design: A cross-sectional study of 378 high-functioning black and white men and women aged 70 to 79 participating in the Health, Aging, and Body Composition Study (Health ABC) who used glucose-lowering medications. Glycemic measures included fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c). Cognitive function was assessed using the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSS) at the same examination visit in which the glycemic measures were determined. Setting: Memphis, Tennessee and Pittsburgh, Pennsylvania. Results: We observed an "inverted-U" relationship (p =.0025 for 3MS, p=.0277 for DSS) between FPG (range 47 - 366 mg/dl) and performance on these two tests. The fasting plasma glucose levels associated with the highest score on the 3MS was 180 mg/dl and 135 mg/dl for the DSS. There was a monotonic inverse relationship between HbA1c and performance on 3MS and DSS without evidence of a threshold effect. Conclusion: Our findings suggest that older adults who are treated for diabetes may experience a small degree of cognitive impairment within the recommended fasting glucose levels, yet measures of long-term glycemic control support tight glycemic control. Given the high prevalence of diabetes and the common use of glucose-lowering drugs in older adults, further studies are needed to elucidate these relationships. C1 Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Knoxville, TN 37996 USA. NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. MedStar Res Inst, Hyattsville, MD USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Shorr, RI (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Knoxville, TN 37996 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 33 TC 24 Z9 25 U1 3 U2 4 PU SERDI EDITION PI PARIS PA 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD JUL-AUG PY 2006 VL 10 IS 4 BP 297 EP 301 PG 5 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 080NX UT WOS:000240255700011 PM 16886100 ER PT J AU Flynn, TR Shanti, RM Levi, MH Adamo, AK Kraut, RA Trieger, N AF Flynn, TR Shanti, RM Levi, MH Adamo, AK Kraut, RA Trieger, N TI Severe odontogenic infections, part 1: Prospective report SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DEEP NECK INFECTION; MAXILLOFACIAL INFECTIONS; OROFACIAL INFECTIONS; CLINDAMYCIN; BACTERIA; MANAGEMENT; PENICILLIN AB Purpose: The purpose of this study was to prospectively evaluate a series of patients with severe odontogenic infections (OI). Patients and Methods: In this study, 37 consecutive hospitalized patients with odontogenic infection were treated with intravenous penicillin (PCN) (unless allergic), and prompt incision and drainage. Standardized data collection included demographic, preadmission, time-related, preoperative, anatomic, treatment, microbiologic, and complications information. Appropriate descriptive statistics were computed. Results: The sample consisted of 37 subjects (38% female) with a mean age of 34.9 years. Three subjects (8%) had immunocompromising diseases. Caries was the most frequent dental disease (65%) and the lower third molar was the most frequently involved tooth (68%). Trismus and dysphagia were present on admission in over 70% of cases. The masticator, perimandibular (submandibular, submental, and/or sublingual), and peripharyngeal (lateral pharyngeal, retropharyngeal, and/or pretracheal) spaces were infected in 78%, 60%, and 43% of cases, respectively. Abscess was found in 76% of cases. PCN-resistant organisms were identified in 19% of all strains isolated and in 54% of patients with sensitivity data. PCN therapeutic failure occurred in 21% of cases and reoperation was required in 8%. Length of hospital stay was 5.1 +/- 3.0 days. No deaths occurred. Conclusions: This study indicated that PCN resistance, resulting in PCN therapeutic failure, was unacceptably high in this sample. Alternative antibiotics, such as clindamycin, should be considered in hospitalized patients with OI. Masticator space infection occurred much more frequently than previously reported. Trismus and dysphagia should be appreciated as significant indicators of severe OI. (C) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Dept Oral & Maxillofacial Surg, Bronx, NY 10467 USA. RP Flynn, TR (reprint author), Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. EM thomas_flynn@hsdm.harvard.edu NR 33 TC 61 Z9 70 U1 4 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2006 VL 64 IS 7 BP 1093 EP 1103 DI 10.1016/j.joms.2006.03.015 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 057OQ UT WOS:000238605500015 PM 16781343 ER PT J AU Flynn, TR Shanti, RM Hayes, C AF Flynn, TR Shanti, RM Hayes, C TI Severe odontogenic infections, part 2: Prospective outcomes study SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID LACTAMASE-PRODUCING BACTERIA; DEEP NECK INFECTION; MAXILLOFACIAL INFECTIONS; ABSCESSES; MODEL AB Purpose: The purpose of this study was to identify significant predictors of 4 outcomes in patients with severe odontogenic infections: abscess formation, penicillin therapeutic failure (PTF), length of hospital stay (LOS), and need for reoperation. Patients and Methods: We used a prospective case series study design and enrolled 37 consecutive patients admitted for severe odontogenic infection between March 1996 and June 1999. Treatment consisted of intravenous penicillin (PCN) or clindamycin in PCN-allergic patients, surgical incision and drainage, and extraction(s) as soon as possible. Study variables were categorized as demographic, preadmission, time-related, preoperative, anatomic, treatment, microbiologic, and complications. The primary outcome variables were abscess formation, PTF, LOS, and reoperation. Multivariate linear and logistic regression techniques were used to measure associations between study variables and the outcome variables. Results: The sample consisted of 37 subjects (23 male, 14 female) with a mean age of 34.9 +/- 15.8 years. Multivariate analyses, controlling for confounding variables, indicated that culture of Peptostreptococci was a negative predictor of abscess formation. LOS was predicted by the number of infected spaces and duration of operation. There was no significant predictor of PTF or reoperation on multivariate analysis, although PCN-resistant organisms were isolated in all cases of PTF. Conclusion: increased LOS in severe odontogenic infections is predicted by the anatomic extent and severity of the infection and the occurrence of complications such as PTF and the need for reoperation. PTF is significantly associated with later identification of PCN-resistant organisms. The role of Peptostreptococci in abscess formation warrants further investigation. (C) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Flynn, TR (reprint author), Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. EM thomas_flynn@hsdm.harvard.edu NR 26 TC 35 Z9 43 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2006 VL 64 IS 7 BP 1104 EP 1113 DI 10.1016/j.joms.2006.03.031 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 057OQ UT WOS:000238605500016 PM 16781344 ER PT J AU Todd, KH Green, C Bonham, VL Haywood, C Ivy, E AF Todd, Knox H. Green, Carmen Bonham, Vence L., Jr. Haywood, Carlton, Jr. Ivy, Evera TI Sickle cell disease related pain: Crisis and conflict SO JOURNAL OF PAIN LA English DT Article ID INTERNAL MORALITY; RACE; CARE; MANAGEMENT; HEALTH; DISPARITIES; DECISIONS; ETHNICITY; MEDICINE; CHILDREN C1 Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Canc Pain Program, Chicago, IL 60611 USA. Albert Einstein Coll Med, Beth Israel Med Ctr, Dept Emergency Med, Pain & Emergency Med Inst, New York, NY USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Baltimore, MD USA. Sickle Cell Dis Assoc Illinois, Chicago, IL USA. RP Todd, KH (reprint author), Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Canc Pain Program, Chicago, IL 60611 USA. OI Haywood Jr., Carlton/0000-0002-3574-7871 NR 33 TC 39 Z9 40 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUL PY 2006 VL 7 IS 7 BP 453 EP 458 DI 10.1016/j.jpain.2006.05.004 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 065SW UT WOS:000239180600001 PM 16814684 ER PT J AU Chong, CH Carnes, DL Moritz, AJ Oates, T Ryu, OH Simmer, J Cochran, DL AF Chong, Chol H. Carnes, David L. Moritz, Alan J. Oates, Thomas Ryu, Ok Hee Simmer, James Cochran, David L. TI Human periodontal fibroblast response to enamel matrix derivative, amelogenin, and platelet-derived growth factor-BB SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE amelogenin; EMDOGAIN; PDGF-BB ID CORONALLY ADVANCED FLAPS; DRIED BONE ALLOGRAFT; LIGAMENT CELLS; IN-VITRO; GINGIVAL FIBROBLASTS; INTRABONY DEFECTS; CONNECTIVE-TISSUE; RHPDGF-BB; REGENERATION; PROTEINS AB Background: The ideal goal of clinical therapy in periodontal defects is regeneration of all lost structures. For regeneration to occur, cell proliferation, migration, and extracellular matrix synthesis are prerequisites. Attempts at regeneration of periodontal defects by guided tissue regeneration using bone grafts and membranes have not always yielded predictable results. Recently, attempts at engineering the defects using various materials have shown promising results. Two such approaches have been used to regenerate periodontal defects, one using extracellular matrix such as enamel matrix proteins and the other using growth factors. However, to our knowledge, no study has looked at combining these two approaches to achieve potentially even greater regeneration. Methods: Primary human periodontal ligament (PDL) fibroblasts were explanted, and alkaline phosphatase (ALK PHOS) activity was determined. Phenotypically different cell lines were incubated for 1, 3, 6, and 10 days in 0.2% fetal bovine serum (FBS) media containing different concentrations of either enamel matrix derivative (EMD), amelogenin, platelet-derived growth factor-BB (PDGF-BB), EMD + PDGF-BB, or amelogenin + PDGF-BB. A culture of 0.2% FBS alone served as a negative control, and a culture of 10% FBS served as a positive control. Cell proliferation was measured using a Coulter counter to determine the cell number. The effects on a wound-fill model were evaluated by scraping a 3-mm wide cell-free zone in PDL monolayers across the diameter of the tissue-culture plate and determining PDL cell migration into the cell-free zone using computer assisted histomorphometry. Results: Compared to the control, only EMD + PDGF-BB significantly increased PDL cell proliferation in an ALK PHOS (-) cell line (P < 0.001), and EMD alone, EMD + PDGF-BB, and amelogenin + PDGF-BB significantly increased PDL cell proliferation in an ALK PHOS (+) cell line (P < 0.001) with EMD + PDGF-BB showing a trend for greater proliferation than either PDGF or EMD alone. Individually, EMD and amelogenin had no significant effect on PDL cell proliferation. In the wound-fill experiment, all factors and their combinations except amelogenin significantly enhanced cell migration compared to the control (P < 0.05) at the wound edge. In addition, EMD + PDGF-BB had additive effects on the ALK PHOS (-) cell line at the wound edge. At the center of the wound, neither EMD nor amelogenin had a significant wound-fill effect. However, the combination of EMD + PDGF-BB additively increased wound fill for both ALK PHOS (+) and ALK PHOS (-) cells. Conclusions: The combination of EMD and PDGF-BB produces greater proliferative and wound-fill effects on PDL cells than each by themselves. If these combined effects can be translated clinically, one may see greater regeneration in periodontal defects with this combination. However, amelogenin does not have significant effects on PDL cell proliferation or migration by itself. This may suggest that either another enamel matrix component in EMD may be responsible for some of its clinical effects, or that amelogenin alone may not trigger the regenerative potential of periodontal tissues and that it requires a combined interaction with other enamel matrix components of EMD to direct the regenerative process. C1 Wilford Hall USAF Med Ctr, Dept Periodont, Lackland AFB, TX 78236 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78285 USA. Natl Inst Dent & Craniofacial Res, NIH, Human Craniofacial Genet Sect, Bethesda, MD USA. Univ Michigan, Sch Dent, Dept Pediat, Ann Arbor, MI 48109 USA. RP Chong, CH (reprint author), Wilford Hall USAF Med Ctr, Dept Periodont, 1615 Truemper St, Lackland AFB, TX 78236 USA. EM chol.chong@lackland.af.mil NR 50 TC 31 Z9 35 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUL PY 2006 VL 77 IS 7 BP 1242 EP 1252 DI 10.1902/jop.2006.050147 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 103IP UT WOS:000241879200020 PM 16805689 ER PT J AU Husain, FT Horwitz, B AF Husain, Fatima T. Horwitz, Barry TI Experimental-neuromodeling framework for understanding auditory object processing: Integrating data across multiple scales SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article DE functional magnetic resonance imaging; fMRI; auditory; speech; hearing; large-scale; neurobiologically realistic ID DORSOLATERAL PREFRONTAL CORTEX; MATCH-TO-SAMPLE; WORKING-MEMORY; FMRI; CATEGORIZATION; CONTINUITY; NEURONS; MACAQUE; ORGANIZATION; SELECTIVITY AB In this article, we review a combined experimental-neuromodeling framework for understanding brain function with a specific application to auditory object processing. Within this framework, a model is constructed using the best available experimental data and is used to make predictions. The predictions are verified by conducting specific or directed experiments and the resulting data are matched with the simulated data. The model is refined or tested on new data and generates new predictions. The predictions in turn lead to better-focused experiments. The auditory object processing model was constructed using available neurophysiological and neuroanatomical data from mammalian studies of auditory object processing in the cortex. Auditory objects are brief sounds such as syllables, words, melodic fragments, etc. The model can simultaneously simulate neuronal activity at a columnar level and neuroimaging activity at a systems level while processing frequency-modulated tones in a delayed-match-to-sample task. The simulated neuroimaging activity was quantitatively matched with neuroimaging data obtained from experiments; both the simulations and the experiments used similar tasks, sounds, and other experimental parameters. We then used the model to investigate the neural bases of the auditory continuity illusion, a type of perceptual grouping phenomenon, without changing any of its parameters. Perceptual grouping enables the auditory system to integrate brief, disparate sounds into cohesive perceptual units. The neural mechanisms underlying auditory continuity illusion have not been studied extensively with conventional neuroimaging or electrophysiological techniques. Our modeling results agree with behavioral studies in humans and an electrophysiological study in cats. The results predict a particular set of bottom-up cortical processing mechanisms that implement perceptual grouping, and also attest to the robustness of our model. Published by Elsevier Ltd. C1 NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Husain, FT (reprint author), NIDCD, Brain Imaging & Modeling Sect, NIH, Bldg 10,Rm 8S235-D,9000 Rockville Pike, Bethesda, MD 20892 USA. EM husainf@mail.nih.gov; horwitzb@mail.nih.gov FU Intramural NIH HHS [Z01 DC000057-08] NR 49 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0928-4257 J9 J PHYSIOLOGY-PARIS JI J. Physiol.-Paris PD JUL-SEP PY 2006 VL 100 IS 1-3 BP 133 EP 141 DI 10.1016/j.jphysparis.2006.09.006 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 123TW UT WOS:000243319900011 PM 17079121 ER PT J AU Desai, TA Sen, PK AF Desai, TA Sen, PK TI Information attainable in some randomly incomplete data models SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE maximum likelihood estimator; asymptotic normality; Fisher information; missing data; EM algorithm; Newton-Raphson method; logistic regression AB The Fisher information is intricately linked to the asymptotic (first-order) optimality of maximum likelihood estimators for parametric complete-data models. When data are missing completely at random in a multivariate setup, it is shown that information in a single observation is well-defined and it plays the same role as in the complete-data model in characterizing the first-order asymptotic optimality properties of associated maximum likelihood estimators; computational aspects are also thoroughly appraised. As an illustration, the logistic regression model with incomplete binary responses and an incomplete categorical covariate is worked out. (c) 2005 Elsevier B.V. All rights reserved. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biostat & Stat & Operat Res, Chapel Hill, NC 27599 USA. RP Desai, TA (reprint author), Indian Inst Management, Ahmedabad 380015, Gujarat, India. EM tdesai@iimahd.ernet.in NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 1 PY 2006 VL 136 IS 7 BP 2309 EP 2326 DI 10.1016/J.JSPI.2005.08.022 PG 18 WC Statistics & Probability SC Mathematics GA 029LP UT WOS:000236564400022 ER PT J AU Kim, Y Sun, YG Chow, C Pommier, YG Simons, SS AF Kim, Yuh Sun, Yunguang Chow, Carson Pommier, Yves G. Simons, S. Stoney, Jr. TI Effects of acetylation, polymerase phosphorylation, and DNA unwinding in glucocorticoid receptor transactivation SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE glucocorticoid receptors; modulation of dose-response curve; partial agonist activity; protein acetylation; RNA polymerase II phosphorylation; DNA unwinding ID UBIQUITIN-CONJUGATING ENZYME; PARTIAL AGONIST ACTIVITY; TUMOR VIRUS PROMOTER; DOSE-RESPONSE CURVE; BREAST-CANCER-CELLS; INDUCTION PROPERTIES; TRANSCRIPTION FACTOR; HISTONE DEACETYLASE; TOPOISOMERASE-I; GENE-EXPRESSION AB Varying the concentration of selected factors alters the induction properties of steroid receptors by changing the position of the dose-response curve (or the value for half-maximal induction = EC50) and the amount of partial agonist activity of antisteroids. We now describe a rudimentary mathematical model that predicts a simple Michaelis-Menten curve for the multi-step process of steroid-regulated gene induction. This model suggests that steps far downstream from receptor binding to steroid can influence the EC50 of agonist-complexes and partial agonist activity of antagonist-complexes. We therefore asked whether inhibitors of three possible downstream steps can reverse the effects of increased concentrations of two factors: glucocorticoid receptors (GRs) and Ubc9. The downstream steps (with inhibitors in parentheses) are protein deacetylation (TSA and VPA), DNA unwinding (CPT), and CTD phosphorylation of RNA polymerase II (DRB and H8). None of the inhibitors mimic or prevent the effects of added GRs. However, inhibitors of DNA unwinding and CTD phosphorylation do reverse the effects of Ubc9 with high GR concentrations. These results support our earlier conclusion that different rate-limiting steps operate at low and high GR concentrations versus high GR with Ubc9. The present data also suggest that downstream steps can modulate the EC50 of GR-mediated induction, thus both supporting the utility of our mathematical model and widening the field of biochemical processes that can modify the EC50. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIDDK, CEB, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biol Modelling, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, CEB, Steroid Hormones Sect, NIH, Bldg 10,Room 8N-307B, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov RI Chow, Carson/A-7970-2009 NR 86 TC 21 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUL PY 2006 VL 100 IS 1-3 BP 3 EP 17 DI 10.1016/j.jsbmb.2006.03.003 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 079FT UT WOS:000240161600002 PM 16723222 ER PT J AU Heymann, JAW Hayles, M Gestmann, I Giannuzzi, LA Lich, B Subramaniam, S AF Heymann, Jurgen A. W. Hayles, Mike Gestmann, Ingo Giannuzzi, Lucille A. Lich, Ben Subramaniam, Sriram TI Site-specific 3D imaging of cells and tissues with a dual beam microscope SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE 3D cellular imaging; cryo-electron microscopy; dual beam imaging; focused ion beam; yeast; tumor tissue ID ELECTRON TOMOGRAPHY; VISUALIZATION; CEREVISIAE; RESOLUTION; SPECIMENS; COMPLEX; YEAST AB Current approaches to 3D imaging at subcellular resolution using confocal microscopy and electron tomography, while powerful, are limited to relatively thin and transparent specimens. Here we report on the use of a new generation of dual beam electron microscopes capable of site-specific imaging of the interior of cellular and tissue specimens at spatial resolutions about an order of magnitude better than those currently achieved with optical microscopy. The principle of imaging is based on using a focused ion beam to create a cut at a designated site in the specimen, followed by viewing the newly generated surface with a scanning electron beam. Iteration of these two steps several times thus results in the generation of a series of surface maps of the specimen at regularly spaced intervals, which can be converted into a three-dimensional map of the specimen. We have explored the potential of this sequential "slice-and-view" strategy for site-specific 3D imaging of frozen yeast cells and tumor tissue, and establish that this approach can identify the locations of intracellular features such as the 100 nm-wide yeast nuclear pore complex. We also show that 200 nm thick sections can be generated in situ by "milling" of resin-embedded specimens using the ion beam, providing a valuable alternative to manual sectioning of cells and tissues using an ultramicrotome. Our results demonstrate that dual beam imaging is a powerful new tool for cellular and subcellular imaging in 3D for both basic biomedical and clinical applications. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. FEI Co, Eindhoven, Netherlands. FEI Co, Hillsboro, OR USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM ssl@nih.gov FU Intramural NIH HHS NR 26 TC 156 Z9 158 U1 5 U2 36 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 JUL PY 2006 VL 155 IS 1 BP 63 EP 73 DI 10.1016/j.jsb.2006.03.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 058AS UT WOS:000238637100009 PM 16713294 ER PT J AU Hilton, TF AF Hilton, Thomas F. TI Staff members are human subjects, too SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE human subjects protection; clinical staff; NIH policy; ethics; undue influence; surveys AB Top management, clinical supervisors, secretaries, government administrators, counselors, and patients are all examples of informants and agents used by health services researchers as they strive to learn how organizational and managerial factors affect the effectiveness, efficiency., quality, and the cost of substance abuse treatment and prevention services. Patients are clearly a vulnerable population, and researchers in clinical settings, as a rule, strive to protect patient safety and rights to privacy. However, as researchers begin to expand the scope of their study to the organizational contexts in which services are delivered, those responsible for providing services (staff members) are frequently enlisted to serve both as informants on policies and practices, and as participants acting as agents of the researchers in innovating therapeutic and business practices. Researchers need to be mindful that staff members, when acting as informants or as agents, are human subjects, too; and, as such, research procedures should be designed in a manner that minimizes their risk and conforms to sound ethical guidelines. In the interest of stimulating dialogue on ways to protect staff members from unintended harm, this essay overviews human subjects protection policy, describes examples of risks, and offers suggestions for preventing harm when designing studies. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Hilton, TF (reprint author), Natl Inst Drug Abuse, Bethesda, MD 20892 USA. EM tom.hilton@nih.gov NR 25 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL PY 2006 VL 31 IS 1 BP 9 EP 15 DI 10.1016/j.jsat.2006.03.001 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 064ZJ UT WOS:000239128900003 PM 16814006 ER PT J AU Ohrui, H Hayakawa, H Kohgo, S Matsuoka, M Kodama, E Mitsuya, H AF Ohrui, Hiroshi Hayakawa, Hiroyuki Kohgo, Satoru Matsuoka, Masao Kodama, Eiichi Mitsuya, Hiroaki TI Creation of low toxic reverse-transcriptase inhibitory nucleosides that prevent the emergence of drug-resistant HIV variants SO JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN LA Japanese DT Article DE AIDS; HIV; anti-HIV-1 drug free from emergence of resistant HIV-1 variant; RT-inhibitory nucleoside; drug-resistant HIV; prevention of the emergence of drug-resistant HIV; highly active anti-retroviral therapy (HAART); 4 '-C-substituted-2 '-deoxynucleoside ID 4'-SUBSTITUTED NUCLEOSIDES; BIOLOGICAL EVALUATION; POTENT INHIBITORS; ANALOGS; NUCLEOTIDES; PYRIMIDINES; AGENT AB Although the Highly Active Anti-Retroviral Therapy (HAART) has dramatically improved the quality of life and the prognosis of patients infected with HIV, development of more active and less toxic drugs that prevent the emergence of drug-resistant HIV variants is strongly required, due to the emergence of new drug-resistant HIV variants, need of taking a large quantity of drugs, and side effects of the drugs. The principal author has proposed a concept to prevent the emergence of the HIV variants resistant to reverse-transcriptase (RT) inhibitory nucleosides. Based on the concept, 4'-C-substituted-2'-deoxynucleoside (4'Sd-N)*(1) was designed as the anti-HIV nucleoside that could prevent the emergence of resistant HIV variants. Various kinds of 4'Sd-N were synthesized and evaluated for biological activity. 2'-Deoxy-4'-C-ethynyl-2-fluoroadenosine (4'Ed-2FA) which is stable to adenosine deaminase turned out to be highly active against all HIV-1 including multi-drug resistant variants and very lowly toxic, and so far no HIV-1 variants resistant to it emerged. These results suggest that once-daily-dosing schedule of 4'Ed-2FA is possible presumably with few side effects and warrant that 4'Ed-2FA be further developed as a potential therapeutic for HIV-1 infection. C1 Yokohama Pharmaceut Coll, Totsuka Ku, Yokohama, Kanagawa 2450066, Japan. Kyoto Univ, Inst Virus Res, Kyoto, Japan. Kumamoto Univ, Sch Med, Kumamoto 860, Japan. NCI, NIH, Bethesda, MD 20892 USA. RP Ohrui, H (reprint author), Yokohama Pharmaceut Coll, Totsuka Ku, 601 Matano Cho, Yokohama, Kanagawa 2450066, Japan. EM h.ohrui@hamayaku.ac.jp RI Kodama, Eiichi /C-4032-2009; OI Kodama, Eiichi /0000-0002-6622-2752; Matsuoka, Masao/0000-0002-0473-754X NR 21 TC 4 Z9 4 U1 0 U2 1 PU SOC SYNTHETIC ORGANIC CHEM JPN PI TOKYO PA CHEMISTRY HALL, 1-5 KANDA-SURUGADAI, CHIYODA-KU, TOKYO, 101, JAPAN SN 0037-9980 J9 J SYN ORG CHEM JPN JI J. Synth. Org. Chem. Jpn. PD JUL PY 2006 VL 64 IS 7 BP 716 EP 723 PG 8 WC Chemistry, Organic SC Chemistry GA 064RZ UT WOS:000239108100002 ER PT J AU Lowell, SY Story, BH AF Lowell, Soren Y. Story, Brad H. TI Simulated effects of cricothyroid and thyroarytenoid muscle activation on adult-male vocal fold vibration SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ABDUCTOR SPASMODIC DYSPHONIA; INTRINSIC LARYNGEAL MUSCLES; GLOTTAL AIR-FLOW; FUNDAMENTAL FREQUENCY; VOICE PRODUCTION; OBJECTIVE MEASURES; PRESSURE CHANGES; SPEECH; PHONATION; INTENSITY AB Adjustments to cricothyroid and thyroarytenoid muscle activation are critical to the control of fundamental frequency and aerodynamic aspects of vocal fold vibration in, humans. The. aerodynamic and physical effects of these muscles are not well understood and are difficult to study in vivo. Knowledge of the contributions of these two muscles is essential to understanding both normal and disordered voice physiology. In this study, a three-mass model for voice simulation in adult males was used to produce systematic changes to cricothyroid and thyroarytenoid muscle activation levels. Predicted effects on fundamental frequency, aerodynamic quantities, and physical quantities of vocal fold vibration were assessed. Certain combinations of these muscle activations resulted in aerodynamic and physical characteristics of vibration that might increase the mechanical stress placed on the vocal fold tissue. (c) 2006 Acoustical Society of America. C1 Univ Arizona, Dept Speech Language & Hearing Sci, Tucson, AZ 85721 USA. RP Lowell, SY (reprint author), NINDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [R01 DC004789] NR 56 TC 13 Z9 13 U1 0 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2006 VL 120 IS 1 BP 386 EP 397 DI 10.1121/1.2204442 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 061TV UT WOS:000238896500035 PM 16875234 ER PT J AU Briggs-Gowan, MJ Carter, AS Bosson-Heenan, J Guyer, AE Horwitz, SM AF Briggs-Gowan, MJ Carter, AS Bosson-Heenan, J Guyer, AE Horwitz, SM TI Are infant-toddler social-emotional and behavioral problems transient? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE infant-toddler; persistence; social-emotional; behavioral problems ID PSYCHIATRIC-DISORDERS; EXTERNALIZING PROBLEMS; ASSESSMENT ITSEA; TEMPERAMENT; PREDICTORS; CHILDHOOD; SEVERITY; CHILDREN; ANXIETY; SAMPLE AB Objective: To examine the persistence of parent-reported social-emotional and behavioral problems in infants and toddlers. Method: The sample comprised 1,082 children ascertained from birth records. Children were 12 to 40 months old in year 1 (1998-1999) and 23 to 48 months old in year 2 (1999-2000). Eighty percent participated in year 1 and 91% were retained in year 2. Social-emotional and behavioral problems were measured by high scores (>= 90th percentile) on the Internalizing, Externalizing, and/or Dysregulation domains of the Infant-Toddler Social and Emotional Assessment (ITSEA). Parents reported on sociodemographic factors, family life impairment, parenting stress, and family functioning. Results: Among children with any high ITSEA domain score in year 1, 49.9% had persistent psychopathology, as indicated by the continued presence of a high score in year 2. In multivariate analyses, persistence was significantly more likely when parents reported co-occurring problems (i.e., problems in multiple ITSEA domains), high family life disruption, and high parenting distress in year 1. Homotypic persistence rates (i.e., same domain persistence) ranged from 38% to 50%. Only for dysregulation was homotypic persistence greater when co-occurring problems were present than for dysregulation alone. Persistence patterns were similar for boys and girls. Conclusion: Findings indicate that infant-toddler social-emotional/behavioral problems are not transient and highlight the need for early identification, multidomain and family assessment, and effective early intervention. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. NIMH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Briggs-Gowan, MJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, 263 Farmington Ave, Farmington, CT 06030 USA. EM Briggsgowan@psychiatry.uchc.edu FU NIMH NIH HHS [R01MH55278] NR 34 TC 111 Z9 112 U1 5 U2 20 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 JUL PY 2006 VL 45 IS 7 BP 849 EP 858 DI 10.1097/01.chi.0000220849.48650.59 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 058CC UT WOS:000238640900015 PM 16832322 ER PT J AU Hickman, D King-Herbert, A Murphy, SJ AF Hickman, Debra King-Herbert, Angela Murphy, Stephanie J. TI The Laboratory Animal Boards Study Group: A multifaceted tool for preparation for the American College of Laboratory Animal Medicine board examination SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article AB Preparation for the specialty board examination for the American College of Laboratory Animal Medicine (ACLAM) is an intensive process that is facilitated by geographic regions where many people studying for the exam are located in close proximity. However, many people work at institutions that are distant from these 'study centers.' Approximately 10 y ago, the Laboratory Animal Boards Study Group (LABSG) online journal club was established to provide a forum for journal review for examination preparation. Over the years, the mission of this group has expanded to include practice examinations and practicals, questions from common resources, and summaries and questions from common laboratory animal science journals. These study aids are beneficial for those preparing for the ACLAM certification examination. They are also beneficial for those preparing for the technician and manager certification examinations offered by the American Association for Laboratory Animal Science (AALAS). This article is intended to be an introduction to the variety of study aids available through the LABSG online journal review club and the LABSG web page (www.labsg.org). It also provides details on the demographics of participants and an exploration of how this resource enhances examination preparation. C1 Portland VA Med Ctr, Portland, OR USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. RP Hickman, D (reprint author), Portland VA Med Ctr, Portland, OR USA. EM Debra.Hickman@med.va.gov RI Hickman, Debra/D-3289-2009 NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2006 VL 45 IS 4 BP 33 EP 39 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 068DL UT WOS:000239352300007 PM 16884177 ER PT J AU Dionne, RA AF Dionne, Raymond A. TI Oral sedation - Response SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID TRIAZOLAM C1 NINR, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), NINR, NIH, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 2006 VL 137 IS 7 BP 946 EP 946 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 063QO UT WOS:000239034800003 ER PT J AU Robey, PG Bianco, P AF Robey, Pamela Gehron Bianco, Paolo TI The use of adult stem cells in rebuilding the human face SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE adult stem cells; skeletal stem cells; bone regeneration; tissue engineering; biomaterials ID MARROW STROMAL CELLS; VIVO BONE-FORMATION; IN-VIVO; TISSUE; DEFECTS; REPAIR; TEETH; SIZE; TRANSPLANTATION; RECONSTRUCTION AB Background. Stern cells have been isolated from a variety of embonic and postnatal (adult tissues including bone marrow. Bone marrow stromal cells (BMSCs), which are non-blood-forming cells in marrow, contain a subset of skeletal stein cells (SSCS) that are able to regenerate all types of skeletal tissue; bone I cartilage, blood-supportive stromal cells and marrow fat cells. Methods. Bone marrow suspensions are placed into culture for analysis,of their biological character and for expansion of their number., The resulting populations of cells are used in a variety of assays to established the existence of an adult SSC, and the ability of BMSC populations, to regenerate hard tissues in the craniofacial region, in conjunction with appropriate scaffolds. Results. Single-cell analysis established the existence of a true adult SSC in bone marrow. Populations of ex vivo expanded BMSCs (a subset, of which are SSCs) are able to regenerate a bone/marrow organ. In conjunction with appropriate. scaffolds, these cells can be used to regenerate bone in a variety of applications. Conclusions. BMSCs have the potential to re-create tissues of the craniofacial region to restore normal structure and function in reconstructing the hard tissues of a face. Ex-vivo expanded BMSCs with scaffolds have been used in a limited number of patients to date, but likely will be used more extensively-in the near future. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Parco Sci Biomed San Raffaele, Inst Cell Biol & Tissue Engn, Rome, Italy. RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM probey@dir.nidcr.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS; NIDCR NIH HHS [1 Z01 DE000380, 1 Z01 DE000649]; Telethon [GGP04263] NR 59 TC 48 Z9 54 U1 0 U2 9 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 2006 VL 137 IS 7 BP 961 EP 972 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 063QO UT WOS:000239034800017 PM 16803822 ER PT J AU Steel, K Williams, TF AF Steel, Knight Williams, T. Franklin TI It's time to march SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 Hackensack Univ, Med Ctr, Dept Med, Div Geriatr,New Jersey Med Sch,Div Gen Med & Geri, Hackensack, NJ 07601 USA. WHO, Hlth Elderley Program, CH-1211 Geneva, Switzerland. Inst Incentives Hlth Care, Guttenberg, NJ USA. Univ Rochester, Dept Med, Sch Med & Dent, Div Geriatr, Rochester, NY 14642 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Steel, K (reprint author), Hackensack Univ, Med Ctr, Dept Med, Div Geriatr,New Jersey Med Sch,Div Gen Med & Geri, 30 Prospect Ave, Hackensack, NJ 07601 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2006 VL 54 IS 7 BP 1142 EP 1143 DI 10.1111/j.1532-5415.2006.00792.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 062XB UT WOS:000238978900018 PM 16866689 ER PT J AU Deshpande, N Novak, A Patla, AE AF Deshpande, Nandini Novak, Alison Patla, Aftab E. TI Determining functional mobility using the modified timed up and go test: Effects of sensory manipulations SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID OLDER-ADULTS C1 NIA, Baltimore Longitudinal Study Aging, NIH, Baltimore, MD 21224 USA. Queens Univ, Sch Rehabil Sci, Ctr Neurosci Studies, Kingston, ON, Canada. Univ Waterloo, Dept Kinesiol, Gait & Posture Lab, Waterloo, ON N2L 3G1, Canada. RP Deshpande, N (reprint author), NIA, Baltimore Longitudinal Study Aging, NIH, Baltimore, MD 21224 USA. NR 8 TC 2 Z9 3 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2006 VL 54 IS 7 BP 1157 EP 1158 DI 10.1111/j.1532-5415.2006.00782.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 062XB UT WOS:000238978900031 PM 16866703 ER PT J AU Domanski, MJ Nanda, N AF Domanski, Michael J. Nanda, Navin TI Echocardiographic determination of left ventricular function SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID MAGNETIC-RESONANCE; EJECTION FRACTION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; VOLUMES C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Domanski, MJ (reprint author), NHLBI, Clin Trials Grp, 2 Rockledge Ctr,Room 8146,6701 Rockledge Dr,MSC 7, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUL PY 2006 VL 19 IS 7 BP 941 EP 942 DI 10.1016/j.echo.2006.03.010 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 064HC UT WOS:000239078800017 PM 16825013 ER PT J AU Schnaper, HW Kopp, JB AF Schnaper, HW Kopp, JB TI Why kidneys fail: Report from an American Society of Nephrology Advances in Research Conference SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article AB A recent American Society of Nephrology Conference, entitled "Why Kidneys Fail: Translating Basic Mechanisms of Disease Pathogenesis into Novel Therapies," explored basic mechanisms and their potential translational implications. In this article, the conference organizers summarize the conference presentations. C1 Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schnaper, HW (reprint author), Pediat W-140,303 E Chicago Ave, Chicago, IL 60611 USA. EM schnaper@northwestern.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU NIDDK NIH HHS [R13 DK074301, R13 DK974301] NR 0 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2006 VL 17 IS 7 BP 1777 EP 1781 DI 10.1681/ASN.2006030267 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 059NG UT WOS:000238738900008 PM 16775028 ER PT J AU Cantor, D AF Cantor, D TI Cancer, quackery and the vernacular meanings of hope in 1950s America SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Patients and Pathways Cancer Therapies in Historical and Sociological Perspective CY OCT 06-08, 2005 CL Univ Manchester, Ctr Hist Sci, Technol & Med, Manchester, ENGLAND HO Univ Manchester, Ctr Hist Sci, Technol & Med DE hope; cancer; quackery; Harry M. Hoxsey; food and drug; administration ID TIME AB Hope was central to cancer control in twentieth-century America. Physicians placed great store in its power to persuade people to seek medical help as early as possible in the development of the disease, when it was most amenable to treatment; to maintain patients' loyalty through what could be a long, painful and uncertain course of therapy; and to encourage doubts about alternative healers. Some also argued that hope could have beneficial therapeutic and psychological effects for patients. However, we know very little about its meanings for the public. Focusing on a large collection of letters written to the Food and Drug Administration in the 1950S concerning an anti-quackery campaign, this article explores how men and women responded to the competing messages of hope promoted by orthodox cancer organizations and by alternative healers. It asks: What did hope mean to such men and women? How did they construct this meaning? How did they decide which treatments were hopeful and which were not? And, how did they use hope to imagine the social world of cancer? In short, this article explores the vernacular meanings, epistemologies, and imaginative uses of hope among Americans in the rmid-twentieth century. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), NCI, Div Canc Prevent, Execut Pl N,Suite 2025, Bethesda, MD 20892 USA. EM cantord@mail.nih.gov FU PHS HHS [P0: 263-MQ-216827] NR 115 TC 10 Z9 10 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JUL PY 2006 VL 61 IS 3 BP 324 EP 368 DI 10.1093/jhmas/jrj048 PG 45 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 055CG UT WOS:000238427000003 PM 16565262 ER PT J AU Geer, RC Rein, DC AF Geer, Renata C. Rein, Diane C. TI Building the role of medical libraries in bioinformatics SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. Purdue Univ, Life Sci Lib, W Lafayette, IN USA. RP Geer, RC (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. EM renata@ncbi.nlm.nih.gov; drein@purdue.edu NR 10 TC 2 Z9 2 U1 0 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2006 VL 94 IS 3 BP 284 EP 285 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 069TF UT WOS:000239470400008 ER PT J AU Geer, RC AF Geer, Renata C. TI Broad issues to consider for library involvement in bioinformatics SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID INFORMATION; DATABASE; GENOME; PHARMACOGENOMICS; EDUCATION; PROTEINS; SERVICES; REFSEQ AB Background: The information landscape in biological and medical research has grown far beyond literature to include a wide variety of databases generated by research fields such as molecular biology and genomics. The traditional role of libraries to collect, organize, and provide access to information can expand naturally to encompass these new data domains. Methods: This paper discusses the current and potential role of libraries in bioinformatics, using empirical evidence and experience from eleven years of work in user services at the National Center for Biotechnology Information. Findings: Medical and science libraries over the last decade have begun to establish educational and support programs to address the challenges users face in the effective and efficient use of a plethora of molecular biology databases and retrieval and analysis tools. As more libraries begin to establish a role in this area, the issues they face include assessment of user needs and skills, identification of existing services, development of plans for new services, recruitment and training of specialized staff, and establishment of collaborations with bioinformatics centers at their institutions. Conclusions: Increasing library involvement in bioinformatics can help address information needs of a broad range of students, researchers, and clinicians and ultimately help realize the power of bioinformatics resources in making new biological discoveries. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. RP Geer, RC (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. EM renata@ncbi.nlm.nih.gov NR 61 TC 8 Z9 9 U1 1 U2 4 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2006 VL 94 IS 3 BP 286 EP 298 PG 13 WC Information Science & Library Science SC Information Science & Library Science GA 069TF UT WOS:000239470400009 PM 16888662 ER PT J AU Messersmith, DJ Benson, DA Geer, RC AF Messersmith, Donna J. Benson, Dennis A. Geer, Renata C. TI A Web-based assessment of bioinformatics end-user support services at US universities SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID RESOURCES AB Objectives: This study was conducted to gauge the availability of bioinformatics end-user support services at US universities and to identify the providers of those services. The study primarily focused on the availability of short-term workshops that introduce users to molecular biology databases and analysis software. Methods: Websites of selected US universities were reviewed to determine if bioinformatics educational workshops were offered, and, if so, what organizational units in the universities provided them. Results: Of 239 reviewed universities, 72 (30%) offered bioinformatics educational workshops. These workshops were located at libraries (N = 15), bioinformatics centers (N = 38), or other facilities (N = 35). No such training was noted on the sites of 167 universities (70%). Of the 115 bioinformatics centers identified, two-thirds did not offer workshops. Conclusions: This analysis of university Websites indicates that a gap may exist in the availability of workshops and related training to assist researchers in the use of bioinformatics resources, representing a potential opportunity for libraries and other facilities to provide training and assistance for this growing user group. C1 Labs Now, Garrett Pk, MD 20896 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Geer, RC (reprint author), Labs Now, POB 386, Garrett Pk, MD 20896 USA. EM dmessersmith@labs-now.com; dab@ncbi.nlm.nih.gov; renata@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 16 TC 5 Z9 5 U1 0 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2006 VL 94 IS 3 BP 299 EP 305 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 069TF UT WOS:000239470400010 PM 16888663 ER PT J AU Linehan, WM AF Linehan, WM TI Collecting duct (Bellini duct) renal cell carcinoma: A nationwide survey in Japan - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material ID KIDNEY; CANCER C1 NCI, Urol Canc Branch, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Canc Branch, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2006 VL 176 IS 1 BP 43 EP 43 DI 10.1016/j.juro.2006.02.023 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 053IE UT WOS:000238298000010 ER PT J AU Nickel, JC Shoskes, D Wang, YL Alexander, RB Fowler, JE Zeitlin, S O'Leary, MP Pontari, MA Schaeffer, AJ Landis, JR Nyberg, L Kusek, JW Propert, KJ AF Nickel, JC Shoskes, D Wang, YL Alexander, RB Fowler, JE Zeitlin, S O'Leary, MP Pontari, MA Schaeffer, AJ Landis, JR Nyberg, L Kusek, JW Propert, KJ CA Chronic Prostatitis Collaborative TI How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome? SO JOURNAL OF UROLOGY LA English DT Article DE prostatitis; pelvic pain; infection; urinary tract infections ID LOCALIZATION; CLASSIFICATION; BACTERIA; URINE AB Purpose: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. Materials and Methods: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Starney results were calculated from 2 X 2 contingency tables. Results: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p < 0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or V133 confirms a positive 4-glass Meares-Starney localization test. The sensitivity and specificity of a V133 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. Conclusions: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained. C1 Queens Univ, Kingston, ON K7L 2V7, Canada. Cleveland Clin Florida, Weston, FL USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Temple Univ, Philadelphia, PA 19122 USA. Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIDDKD, Bethesda, MD 20892 USA. Univ Mississippi, Hlth Sci Ctr, Jackson, MS 39216 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Nickel, JC (reprint author), Queens Univ, Kingston Gen Hosp, Dept Urol, Kingston, ON K7L 2V7, Canada. EM jcn@post.queensu.ca RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK 53738, U01 DK 53572, U01 DK 53730, U01 DK 53732, U01 DK 53734, U01 DK 53736, U01 DK 53746] NR 19 TC 59 Z9 62 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2006 VL 176 IS 1 BP 119 EP 124 DI 10.1016/S0022-5347(06)00498-8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 053IE UT WOS:000238298000032 PM 16753385 ER PT J AU Dromi, S Wood, BJ Oberoi, J Neeman, Z AF Dromi, Sergio Wood, Bradford J. Oberoi, Jay Neeman, Ziv TI Heavy metal pad shielding during fluoroscopic interventions SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RADIATION-EXPOSURE; RADIOLOGY; PERSONNEL AB Significant direct and scatter radiation doses to patient and physician may result from routine interventional radiology practice. A lead-free disposable tungsten antimony shielding pad was tested in phantom patients during simulated diagnostic angiography procedures. Although the exact risk of low doses of ionizing radiation is unknown, dramatic dose reductions can be seen with routine use of this simple, sterile pad made from lightweight tungsten antimony material. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Dromi, S (reprint author), NIH, Dept Diagnost Radiol, Bldg 10,Room 1C662,10 Ctr Dr, Bethesda, MD 20892 USA. EM dromis@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 18 TC 16 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL PY 2006 VL 17 IS 7 BP 1201 EP 1206 DI 10.1097/01.RVI.0000228372.62738.36 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 070TZ UT WOS:000239548900020 PM 16868175 ER PT J AU Tscharke, DC Woo, WP Sakala, IG Sidney, J Sette, A Moss, DJ Bennink, JR Karupiah, G Yewdell, JW AF Tscharke, DC Woo, WP Sakala, IG Sidney, J Sette, A Moss, DJ Bennink, JR Karupiah, G Yewdell, JW TI Poxvirus CD8(+) T-cell determinants and cross-reactivity in BALB/c mice SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA VIRUS; SMALLPOX VACCINE; ECTROMELIA; INFECTION; PROFILES; RECEPTOR; IDENTIFICATION; GLYCOPROTEIN; ANTIGEN; BINDING AB Mouse models of orthopoxvirus disease provide great promise for probing basic questions regarding host responses to this group of pathogens, which includes the causative agents of monkeypox and smallpox. However, some essential tools for their study that are taken for granted with other mouse models are not available for these viruses. Here we map and characterize the initial CD8(+) T-cell determinants for poxviruses in H-2(d)-haplotype mice. CD8+ T cells recognizing these three determinants make up around 40% of the total responses to vaccinia virus during and after resolution of infection. We then use these determinants to test if predicted conservation across orthopoxvirus species matches experimental observation and find an unexpectedly cross-reactive variant peptide encoded by ectromelia (mousepox) virus. C1 Australian Natl Univ, Sch Biochem & Mol Biol, Canberra, ACT 0200, Australia. Natl Inst Allergy & Infect Dis, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. Queensland Inst Med Res, Div Immunol & Infect Dis, Herston, Qld 4006, Australia. Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Canberra, ACT 2601, Australia. La Jolla Inst Allergy & Immunol, Div Translat Immunol & Biodefense, San Diego, CA 92121 USA. RP Tscharke, DC (reprint author), Australian Natl Univ, Sch Biochem & Mol Biol, Canberra, ACT 0200, Australia. EM david.tscharke@anu.edu.au; jyewdell@niaid.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Karupiah, Gunasegaran/J-4707-2013; Tscharke, David/C-9133-2009 OI Tscharke, David/0000-0001-6825-9172 FU Intramural NIH HHS; NIAID NIH HHS [N01 AI 40023, N01AI40023, R01 AI 56268, R01 AI056268] NR 32 TC 70 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 13 BP 6318 EP 6323 DI 10.1128/JVI.00427-06 PG 6 WC Virology SC Virology GA 054MJ UT WOS:000238380700013 PM 16775319 ER PT J AU Bailey, JR Sedaghat, AR Kieffer, T Brennan, T Lee, PK Wind-Rotolo, M Haggerty, CM Kamireddi, AR Liu, Y Lee, J Persaud, D Gallant, JE Cofrancesco, J Quinn, TC Wilke, CO Ray, SC Siliciano, JD Nettles, RE Siliciano, RF AF Bailey, JR Sedaghat, AR Kieffer, T Brennan, T Lee, PK Wind-Rotolo, M Haggerty, CM Kamireddi, AR Liu, Y Lee, J Persaud, D Gallant, JE Cofrancesco, J Quinn, TC Wilke, CO Ray, SC Siliciano, JD Nettles, RE Siliciano, RF TI Residual human immunodeficiency virus type 1 viremia in some patients on Antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4(+) T cells SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 DRUG-RESISTANCE; IN-VIVO; LATENT RESERVOIR; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; INFECTED INDIVIDUALS; LIFELONG PERSISTENCE; PLASMA VIREMIA; VIRAL LOAD; REPLICATION AB Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1 persists in resting CD4(+) T cells, and low residual levels of free virus are found in the plasma. Limited characterization of this residual viremia has been done because of the low number of virions per sample. Using intensive sampling, we analyzed residual viremia and compared these viruses to latent proviruses in resting CD4(+) T cells in peripheral blood. For each patient, we found some viruses in the plasma that were identical to viruses in resting CD4+ T cells by pol gene sequencing. However, in a majority of patients, the most common viruses in the plasma were rarely found in resting CD4+ T cells even when the resting cell compartment was analyzed with assays that detect replication-competent viruses. Despite the large diversity of pol sequences in resting CD4+ T cells, the residual viremia was dominated by a homogeneous population of viruses with identical pol sequences. In the most extensively studied case, a predominant plasma sequence was also found in analysis of the env gene, and linkage by long-distance reverse transcriptase PCR established that these predominant plasma sequences represented a single predominant plasma virus clone. The predominant plasma clones were released for months to years without evident sequence change. Thus, in some patients on antiretroviral therapy, the major mechanism for residual viremia involves prolonged production of a small number of viral clones without evident evolution, possibly by cells other than circulating CD4(+) T cells. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Texas, Sect Integrat Biol, Austin, TX 78713 USA. Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Siliciano, RF (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. EM rsiliciano@jhmi.edu RI Ray, Stuart/B-7527-2008; Wilke, Claus/B-4643-2008; OI Ray, Stuart/0000-0002-1051-7260; Wilke, Claus/0000-0002-7470-9261; Liu-Chittenden, Yi/0000-0001-6357-5360 FU NCRR NIH HHS [M01 RR 00052, M01 RR000052]; NIAID NIH HHS [R01 AI043222, AI 065960, AI 43222, AI 51178, K08 AI 060367, K08 AI060367, R01 AI051178, R01 AI065960, R37 AI051178] NR 59 TC 246 Z9 250 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 13 BP 6441 EP 6457 DI 10.1128/JVI.00591-06 PG 17 WC Virology SC Virology GA 054MJ UT WOS:000238380700026 PM 16775332 ER PT J AU Weaver, EA Lu, ZJ Camacho, ZT Moukdar, F Liao, HX Ma, BJ Muldoon, M Theiler, J Nabel, GJ Letvin, NL Korber, BT Hahn, BH Haynes, BF Gao, F AF Weaver, EA Lu, ZJ Camacho, ZT Moukdar, F Liao, HX Ma, BJ Muldoon, M Theiler, J Nabel, GJ Letvin, NL Korber, BT Hahn, BH Haynes, BF Gao, F TI Cross-subtype T-cell immune responses induced by a human immunodeficiency virus type 1 group M consensus env immunogen SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; HIV TYPE-1; LYMPHOCYTE EPITOPES; VACCINE DESIGN; RHESUS-MONKEYS; DNA VACCINES; AIDS; ANTIBODY; ELICITS; VIREMIA AB The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from heterologous subtype A, B, and C viruses. The CON6-derived vaccine was immunogenic and induced a greater number of T-cell epitope responses than any single wild-type subtype A, B, and C env immunogen and similar T-cell responses to a polyvalent vaccine. The responses were comparable to within-clade responses but significantly more than between-clade responses. The magnitude of the T-cell responses induced by CON6 (measured by individual epitope peptides) was also greater than the magnitude of responses induced by individual wild-type env immunogens. Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, these results suggest that synthetic centralized env immunogens represent a promising approach for HIV-1 vaccine design that merits further characterization. C1 Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. Univ Manchester, Sch Math, Manchester, Lancs, England. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Gao, F (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, 112 RP3,Res Dr,Box 3347, Durham, NC 27710 USA. EM fgao@duke.edu RI Muldoon, Mark/C-7505-2009; OI Muldoon, Mark/0000-0002-5004-7195; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [T32 AI007392, R21 AI055386, P30 AI051445, P01 AI061734, P01 AI035351, N01AI85338, AI52816, 5T32 AI07392, AI35351, AI51445, AI54497, AI61734, AI85338, P01 AI052816, P01 AI52816, U01 AI035351] NR 40 TC 53 Z9 54 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 14 BP 6745 EP 6756 DI 10.1128/JVI.02484-05 PG 12 WC Virology SC Virology GA 059ZF UT WOS:000238770000003 PM 16809280 ER PT J AU Bashirova, AA Bleiber, G Qi, Y Hutcheson, H Yamashita, T Johnson, RC Cheng, J Alter, G Goedert, JJ Buchbinder, S Hoots, K Vlahov, D May, M Maldarelli, F Jacobson, L O'Brien, SJ Telenti, A Carrington, M AF Bashirova, AA Bleiber, G Qi, Y Hutcheson, H Yamashita, T Johnson, RC Cheng, J Alter, G Goedert, JJ Buchbinder, S Hoots, K Vlahov, D May, M Maldarelli, F Jacobson, L O'Brien, SJ Telenti, A Carrington, M TI Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CYCLE ARREST; ESCRT-I; ENDOSOMAL TRAFFICKING; SORTING COMPLEX; LATE DOMAIN; PROTEIN; UBIQUITIN; INTERACTS; HOMOLOG; E2 AB Tumor susceptibility gene 101 (TSG101) encodes a host cellular protein that is appropriated by human immunodeficiency virus type 1 (HIV-1) in the budding process of viral particles from infected cells. Variation in the coding or noncoding regions of the gene could potentially affect the degree of TSG101-mediated release of viral particles. While the coding regions of the gene were found to lack nonsynonymous variants, two polymorphic sites in the TSGI01 5' area were identified that were associated with the rate of AIDS progression among Caucasians. These single-nucleotide polymorphisms (SNPs), located at positions -183 and +181 relative to the translation start, specify three haplotypes termed A, B, and C, which occur at frequencies of 67%, 21%, and 12%, respectively. Haplotype C is associated with relatively rapid AIDS progression, while haplotype B is associated with slower disease progression. Both effects were dominant over the intermediate haplotype A. The haplotypes also demonstrated parallel effects on the rate of CD4 T-cell depletion and viral load increase over time, as well as a possible influence on HIV-1 infection. The data raise the hypothesis that noncoding variation in TSG101 affects the efficiency of TSG101-mediated release of viral particles from infected cells, thereby altering levels of plasma viral load and subsequent disease progression. C1 NCI, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland. Univ Lausanne Hosp, Div Infect Dis, Lausanne, Switzerland. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX USA. Univ Bristol, Dept Social Med, Bristol, Avon, England. NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA. RP Carrington, M (reprint author), NCI, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. EM carringt@mail.ncifcrf.gov RI May, Margaret/E-8099-2013; SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; Johnson, Randall/B-1517-2014 OI May, Margaret/0000-0002-9733-1003; Johnson, Randall/0000-0001-7754-0847 FU NCI NIH HHS [N01CO12400] NR 39 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 14 BP 6757 EP 6763 DI 10.1128/JVI.00094-06 PG 7 WC Virology SC Virology GA 059ZF UT WOS:000238770000004 PM 16809281 ER PT J AU Brenchley, JM Ruff, LE Casazza, JP Koup, RA Price, DA Douek, DC AF Brenchley, JM Ruff, LE Casazza, JP Koup, RA Price, DA Douek, DC TI Preferential infection shortens the life span of human immunodeficiency virus-specific CD4(+) T cells in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; DISEASE PROGRESSION; HETEROLOGOUS IMMUNITY; RESPONSES; CD8(+); VIREMIA; INDIVIDUALS; PROLIFERATION; DECLINE AB CD4(+) T-cell help is essential for effective immune responses to viruses. In human immunodeficiency virus (HIV) infection, CD4(+) T cells specific for HIV are infected by the virus at higher frequencies than other memory CD4(+) T cells. Here, we demonstrate that HIV-specific CD4(+) T cells are barely detectable in most infected individuals and that the corresponding CD4(+) T cells exhibit an immature phenotype compared to both cytomegalovirus (CMV)-specific CD4(+) T cells and other memory CD4(+) T cells. However, in two individuals, we observed a rare and diametrically opposed pattern in which HIV-specific CD4(+) T-cell populations of large magnitude exhibited a terminally differentiated immunophenotype; these cells were not preferentially infected in vivo. Clonotypic analysis revealed that the HIV-specific CD4(+) T cells from these individuals were cross-reactive with CMV. Thus, preferential infection can be circumvented in the presence of cross-reactive CD4(+) T cells driven to maturity by coinfecting viral antigens, and this physical proximity rather than activation status per se is an important determinant of preferential infection based on antigen specificity. These data demonstrate that preferential infection reduces the life span of HIV-specific CD4(+) T cells in vivo and thereby compromises the generation of effective immune responses to the virus itself; further, this central feature in the pathophysiology of HIV infection can be influenced by the cross-reactivity of responding CD4(+) T cells. C1 NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bldg 40,Rm 3509,40 Convent Dr, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G108/441] NR 45 TC 55 Z9 55 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 14 BP 6801 EP 6809 DI 10.1128/JVI.00070-06 PG 9 WC Virology SC Virology GA 059ZF UT WOS:000238770000009 PM 16809286 ER PT J AU Haque, M Wang, V Davis, DA Zheng, ZM Yarchoan, R AF Haque, M Wang, V Davis, DA Zheng, ZM Yarchoan, R TI Genetic organization and hypoxic activation of the Kaposi's sarcoma-associated herpesvirus ORF34-37 gene cluster SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; UBIQUITIN-PROTEASOME PATHWAY; TUMOR-SUPPRESSOR PROTEIN; INDUCIBLE FACTOR 1-ALPHA; RIBOSOME ENTRY SITE; LYMPHOMA CELL-LINE; TRANSCRIPTIONAL ACTIVATION; RESPONSE ELEMENTS; DNA-REPLICATION; LYTIC REPLICATION AB Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We previously reported that hypoxia activates KSHV lytic replication and that the promoter for open reading frame 34 (ORF34) contains a functional hypoxia-responsive element (HRE). ORF34 is part of a cluster of lytic genes (ORF34-37) that includes ORF36, a phosphotransferase, and ORF37, a shutoff exonuclease. Rapid amplification of cDNA ends analysis revealed that they share a common polyadenylation signal but have two start sites. Two transcripts were identified, one 3.4 kb encoding ORF35-37, and the other 4.2 kb encoding ORF34 and also having coding potential for ORF35-37. Exposure of PEL cell lines to hypoxia induced messages of lengths consistent with those of these transcripts. Reporter assays with Hep3B cells showed activation of both transcripts by hypoxia. The ORF34-37 promoter region has six consensus HREs. Sequential deletion, site-directed mutagenesis experiments, and Northern blot analysis of RNA produced by constructs indicated that the second HRE (HRE-2) plays a critical role in the hypoxic activation of both RNA transcripts. The ORF35-37 transcript was upregulated by cotransfected hypoxia-inducible factor (HIF). Electrophoretic mobility shift assays demonstrated that HRE-2 and ancillary sequences bind and compete for HIF with hypoxic Hep3B nuclear extract. The activation of this gene cluster by hypoxia may have implications for the pathogenesis of PEL and KS. Moreover, the activation of ORF36 by hypoxia might be exploited to develop targeted therapy for PEL, which arises in a hypoxic environment (pleural effusions). C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Rm 10S255,MSC 1868, Bethesda, MD 20892 USA. EM ry1n@nih.gov FU Intramural NIH HHS NR 73 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 14 BP 7037 EP 7051 DI 10.1128/JVI.00553-06 PG 15 WC Virology SC Virology GA 059ZF UT WOS:000238770000032 PM 16809309 ER PT J AU Siu, YT Chin, KT Siu, KL Choy, EYW Jeang, KT Jin, DY AF Siu, YT Chin, KT Siu, KL Choy, EYW Jeang, KT Jin, DY TI TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTIONAL ACTIVITY; GENE-EXPRESSION; DEPENDENT TRANSCRIPTION; TRANSACTIVATOR TAX; BINDING-ACTIVITY; MAMMALIAN-CELLS; ONCOPROTEIN TAX; PROTEIN; CREB AB Human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription from the long terminal repeats (LTR). Mechanisms through which Tax activates LTR have been established, but coactivators of this process remain to be identified and characterized. Here we show that all three members of the TORC family of transcriptional regulators are coactivators of Tax for LTR-driven expression. TORC coactivation requires CREB, but not ATF4 or other bZIP factors. Tax physically interacts with TORC1, TORC2, and TORC3 (TORC1/2/3), and the depletion of TORC1/2/3 inhibited Tax activity. TORC coactivation can be further enhanced by transcriptional coactivator p300. In addition, coactivators in the p300 family are required for full activity of Tax independently of TORC1/2/3. Thus, both TORC and p300 families of coactivators are essential for optimal activation of HTLV-1 transcription by Tax. C1 Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. NIAID, Mol Neurobiol Lab, Bethesda, MD 20892 USA. RP Jin, DY (reprint author), Univ Hong Kong, Dept Biochem, 3-F Lab Block,Fac Med Bldg,21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. EM dyjin@hkucc.hku.hk RI Jeang, Kuan-Teh/A-2424-2008 NR 42 TC 45 Z9 51 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 JUL PY 2006 VL 80 IS 14 BP 7052 EP 7059 DI 10.1128/JVI.00103-06 PG 8 WC Virology SC Virology GA 059ZF UT WOS:000238770000033 PM 16809310 ER PT J AU Mohamadzadeh, M Coberley, SS Olinger, GG Kalina, WV Ruthel, G Fuller, CL Swenson, DL Pratt, WD Kuhns, DB Schmaljohn, AL AF Mohamadzadeh, M Coberley, SS Olinger, GG Kalina, WV Ruthel, G Fuller, CL Swenson, DL Pratt, WD Kuhns, DB Schmaljohn, AL TI Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by Marburg and Ebola viruses SO JOURNAL OF VIROLOGY LA English DT Article ID EQUINE ENCEPHALITIS-VIRUS; PROTECT GUINEA-PIGS; HEMORRHAGIC-FEVER; DENDRITIC CELLS; INFLAMMATORY RESPONSES; NONHUMAN-PRIMATES; INFECTED PATIENTS; IMMUNITY; TREM-1; PATHOGENESIS AB Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections. C1 USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. Natl Canc Inst, Frederick, MD USA. RP Mohamadzadeh, M (reprint author), USAMRIID, 1425 Porter St, Frederick, MD 21702 USA. EM Mansour.Mohamadzadeh@amedd.army.mil OI Olinger, Gene/0000-0001-7338-0292 FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NIAID NIH HHS [AI 59590-01, R21 AI059590] NR 44 TC 48 Z9 51 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2006 VL 80 IS 14 BP 7235 EP 7244 DI 10.1128/JVI.00543-06 PG 10 WC Virology SC Virology GA 059ZF UT WOS:000238770000052 PM 16809329 ER PT J AU Pinn, VW AF Pinn, Vivian W. TI Women's Health 2nd NIH Interdisciplinary Research Symposium - October 20, 2005 - Introduction SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, Bldg 1,Room 201, Bethesda, MD 20892 USA. EM ORWH-Research@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL PY 2006 VL 15 IS 6 BP 669 EP 670 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 079LG UT WOS:000240177200001 ER PT J AU Acuna-Castillo, C Leiva-Salcedo, E Gomez, CR Perez, V Li, M Torres, C Walter, R Murasko, DM Sierra, F AF Acuna-Castillo, Claudio Leiva-Salcedo, Elias Gomez, Christian R. Perez, Viviana Li, Min Torres, Claudio Walter, Robin Murasko, Donna M. Sierra, Felipe TI T-kininogen: A biomarker of aging in fisher 344 rats with possible implications for the immune response SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SIGNAL-TRANSDUCTION; CELL PROLIFERATION; GENE-EXPRESSION; AGE; LYMPHOCYTES; LIFE; RESPONSIVENESS; MODULATION; MECHANISMS; SENESCENCE AB T-kininogen (T-KG) is a reliable biomarker of aging in male Sprague-Dawley rats. Here we confirm, in a longitudinal study, a similar behavior in Fisher 344 rats of both sexes. In males, the increase in serum levels of T-KG follows an exponential curve, whereas in females the increase is best fitted by a linear curve. In both genders, dietary restriction delays the increase in T-KG. We have previously shown that T-KG inhibits T lymphocyte proliferation. Here we show that serum T-KG levels correlate negatively with the ability of splenocytes (most likely B cells) to proliferate in response to lipopolysaccharide. A similar correlation was not observed with other markers of inflammation, including alpha 1-acid glycoprotein (AGP), haptoglobin, or interleukin-10. We conclude that the increase in serum T-KG represents a useful biomarker of aging in Fisher 344, and it correlates with decreased lymphocyte proliferation with age, although a cause-effect relationship has not been established. C1 Univ Chile, Fac Med, Inst Ciencias Biol, Programa Biol Celular & Mol, Santiago 7, Chile. Univ Chile, Fac Med, Ctr FONDAP Estudios Mol Celula, Santiago 7, Chile. Lankenau Inst Med Res, Wynnewood, PA USA. Drexel Univ, Dept Biosci & Biotechnol, Philadelphia, PA 19104 USA. RP Sierra, F (reprint author), NIA, 7201 Wisconsin Ave,Suite 2C231, Bethesda, MD 20892 USA. EM sierraf@nia.nih.gov FU NIA NIH HHS [R01 AG 7719, R01 AG 13902] NR 45 TC 6 Z9 6 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2006 VL 61 IS 7 BP 641 EP 649 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 071ZO UT WOS:000239642600003 PM 16870624 ER PT J AU Ershler, WB Longo, DL AF Ershler, William B. Longo, Dan L. TI A report card for geriatric oncology: Borderline pass, improvement needed SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID TUMOR SUPPRESSION; CANCER; SCIENCE C1 NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Ershler, WB (reprint author), Harbor Hosp, Clin Res Branch, NM 526,3100 S Hanover St, Baltimore, MD 21225 USA. EM wershler@iasia.org NR 10 TC 2 Z9 2 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2006 VL 61 IS 7 BP 688 EP 688 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 071ZO UT WOS:000239642600008 PM 16870629 ER PT J AU Guralnik, JM Butterworth, S Wadsworth, MEJ Kuh, D AF Guralnik, Jack M. Butterworth, Suzanne Wadsworth, Michael E. J. Kuh, Diana TI Childhood socioeconomic status predicts physical functioning a half century later SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MUSCLE STRENGTH; BIRTH COHORT; LONGITUDINAL CHANGES; GRIP STRENGTH; ADULT HEALTH; MORTALITY; LIFE; AGE; DISABILITY; WOMEN AB Background. Socioeconomic status (SES) affects health outcomes at all stages of life. Relating childhood socioeconomic environment to midlife functional status provides a life course perspective on childhood factors associated with poor and good health status later in life. Methods. The British 1946 birth cohort was prospectively evaluated with periodic examinations from birth through age 53 years, when physical performance tests assessing strength, balance, and rising from a chair were administered. Early childhood socioeconomic factors were examined as predictors of low, middle, or high function at midlife. We tested the hypothesis that adulthood behavioral risk factors would explain the childhood SES-midlife physical function associations. Results. Multiple measures of childhood deprivation were associated with midlife function but in multivariate analyses only father's occupation was associated with low function (relative risk [RR] for manual occupation = 1.6; 95% confidence interval [Cl], 1.1-2.3), and only mother's education was associated with high function (RR for lower mother's education = 0.49; 95% Cl, 0.34-0.72). Early adulthood behavioral risk factors and middle-age SES and disease status only modestly attenuated the relationship between father's occupation and low function and had no impact on the relationship of mother's education with high function. Conclusions. The social environment in which a child grows up has a strong association with midlife, objectively measured functional status, which is a reflection of the aging process and chronic diseases accumulated over the life course. Of particular interest is the role of higher maternal education in promoting high midlife functioning. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. UCL Royal Free & Univ Coll Med Sch, MRC, Natl Survey Hlth & Dev, London, England. RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. EM jg48s@nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U120063239] NR 32 TC 74 Z9 75 U1 1 U2 10 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2006 VL 61 IS 7 BP 694 EP 701 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 071ZO UT WOS:000239642600010 PM 16870631 ER PT J AU Manini, TM Cook, SB VanArnam, T Marko, M Ploutz-Snyder, L AF Manini, Todd M. Cook, Summer B. VanArnam, Tom Marko, Moshe Ploutz-Snyder, Lori TI Evaluating task modification as an objective measure of functional limitation: Repeatability and comparability SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OLDER-ADULTS; PRECLINICAL DISABILITY; PERFORMANCE; WOMEN; RELIABILITY; EXERCISE; HEALTHY; RISE AB Background. Modification of everyday tasks in older adults is associated with risk of deleterious health outcomes. The purpose of this study was to develop a task modification scale to examine its reliability and comparability to timed performance and common measures of physical function and impairment. Methods. Eighty-two (21 men, 61 women) older adults (74.4 +/- 8.2 years) were observed performing a chair rise (sitting heights: 43 cm, 38 cm, and 30 cm), stair ascent/descent, and kneel and supine rise tasks. Six hierarchically ranked categories (0-5) of modification were created for each task and then summed across tasks (summary modification [MOD] score: range 0-35). Comparisons were made with timed performance, knee extension strength, single-leg balance, self-reported function, five chair stands, and gait speed. Results. Inter-rater reliability (intra-class correlation = 0.98) and participant repeatability (intra-class correlation = 0.92) of the MOD score were excellent. Ninety-six percent of participants modified at least one task (MOD score: 10.5 +/- 7.51, range 0-27). After adjusting for task modification, timed performance showed a lower association with gait speed (time vs MOD score, semipartial r(2) = 0.31 vs 0.68), strength (semipartial r(2) = 0.14 vs 0.65), and single-leg balance (semipartial r(2) = 0.10 vs 0.40) than did the MOD score. The MOD score showed higher correlations with muscle strength and balance impairment than did other measures of functional limitation such as gait speed, time to complete five chair stands, and self-reported physical function. Conclusion. Documentation of task modification is reliable across raters and repeatable within participants; in addition, it compares well with other measures of physical function and impairment. Task modification reveals important and intuitive information regarding physical limitation, and deserves greater attention. C1 Syracuse Univ, Dept Exercise Sci, Syracuse, NY 13244 USA. SUNY Syracuse, Dept Phys Therapy, Syracuse, NY 13210 USA. SUNY Syracuse, Dept Phys Med & Rehabil, Syracuse, NY 13210 USA. RP Manini, TM (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM maninit@mail.nih.gov NR 23 TC 13 Z9 13 U1 4 U2 9 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2006 VL 61 IS 7 BP 718 EP 725 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 071ZO UT WOS:000239642600014 PM 16870635 ER PT J AU Fried, LF Shlipak, MG Stehman-Breen, C Mittalhenkle, A Seliger, S Samak, M Robbins, J Siscovick, D Harris, TB Newman, AB Cauley, JA AF Fried, Linda F. Shlipak, Michael G. Stehman-Breen, Catherine Mittalhenkle, Anuja Seliger, Stephen Samak, Mark Robbins, John Siscovick, David Harris, Tamara B. Newman, Anne B. Cauley, Jane A. TI Kidney function predicts the rate of bone loss in older individuals: The cardiovascular health study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID SERUM CYSTATIN-C; GLOMERULAR-FILTRATION-RATE; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; RENAL-INSUFFICIENCY; HIP FRACTURE; ELDERLY-MEN; OSTEOPOROSIS; RISK; ALENDRONATE AB Background. Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals >= 65 years old. Methods. Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women. Results. In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women. Conclusion. Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Amgen Inc, Thousand Oaks, CA USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Univ Maryland, Dept Med, College Pk, MD 20742 USA. Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM linda.fried@med.va.gov RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015 OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408 FU NHLBI NIH HHS [N01-HC-35129, N01 HC-15103, N01-HC-85079, N01-HC-85086] NR 31 TC 27 Z9 27 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2006 VL 61 IS 7 BP 743 EP 748 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 071ZO UT WOS:000239642600017 PM 16870638 ER PT J AU Hong, SB Furihata, M Baba, M Zbar, B Schmidt, LS AF Hong, SB Furihata, M Baba, M Zbar, B Schmidt, LS TI Vascular defects and liver damage by the acute inactivation of the VHL gene during mouse embryogenesis SO LABORATORY INVESTIGATION LA English DT Article DE Cre/lox; embryogenesis; HIF; mouse model of human cancer; VHL ID HIPPEL-LINDAU-DISEASE; ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR; TARGETED INACTIVATION; EMBRYONIC LETHALITY; PROTEIN; EXPRESSION; MICE; PVHL; VASCULOGENESIS AB Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene leads to the development of central nervous system hemangioblastomas, pheochromocytomas and renal cell carcinomas. The biological role of the VHL gene during development is poorly understood because of early lethality of VHL-null embryos. To overcome early embryo lethality observed in the conventional knockout mouse, we introduced a tamoxifen-inducible Cre (CreER (TM)) transgene for the stage specific inactivation of the VHL gene. Acute tamoxifen-induced inactivation of the VHL gene at E10.5 resulted in embryonic lethality between E14.5 and E15.0 with extensive hemorrhage and necrosis, while littermate controls showed normal development. Examination of the VHL-inactivated embryos between E10.5 and E14.5 revealed dilated blood vessels, hemorrhage and necrotizing liver damage. Concomitant with severe hemorrhage and abnormal vasculature at E15.0, blood circulation in the yolk sac was impaired in the VHL-inactivated embryos, which may be the cause of embryo death. Placental development looked normal before embryo death (E14.5); however, at E16.5 following embryo death, we observed reduced growth of the placental labyrinthine layer. Inactivation of the VHL gene resulted in hypoxia-inducible factor (HIF)-1 alpha stabilization and induction of its target genes, VEGF and CAIX, in mouse embryonic fibroblasts (MEFs). In addition, we observed lactate overproduction and acidification of culture media by the inactivation of the VHL gene. Thus, by using a novel conditional VHL knockout mouse model, we could show that the VHL gene plays an important role in the developing vasculature and liver during embryogenesis through regulation of HIF-1 alpha and its target genes. This mouse model will be useful for the screening of anti-HIF or anti-VEGF drugs in vivo. Additionally, this acute VHL inactivation system may provide a useful tool for the in vivo study of genes that cause early embryonic lethality. C1 NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Immunobiol Lab, Frederick, MD 21702 USA. Kochi Med Sch, Dept Tumor Pathol, Kochi, Japan. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schmidt, LS (reprint author), NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Immunobiol Lab, Bldg 560,Rm 12-69, Frederick, MD 21702 USA. EM schmidtl@mail.ncifcrf.gov RI Baba, Masaya/L-7490-2013 OI Baba, Masaya/0000-0002-5308-6683 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 29 TC 18 Z9 22 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 2006 VL 86 IS 7 BP 664 EP 675 DI 10.1038/labinvest.3700431 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 053NO UT WOS:000238312000005 PM 16652107 ER PT J AU Jha, A Zhao, J Cameron, TS De Clercq, E Balzarini, J Manavathu, EK Stables, JP AF Jha, Amitabh Zhao, Jin Cameron, T. Stanley De Clercq, Erik Balzarini, Jain Manavathu, Elias K. Stables, James P. TI Design, synthesis and biological evaluation of novel curcumin analogues as anti-neoplastic agents SO LETTERS IN DRUG DESIGN & DISCOVERY LA English DT Article ID CHEMOPREVENTIVE AGENT; CYTOCHROME-C; CANCER; DIFERULOYLMETHANE; INHIBITION; APOPTOSIS; ANGIOGENESIS; DEGRADATION; SYNTHETASE; ANTICANCER AB A series of novel curcumin analogues were synthesized and bioevaluated for anti-neoplastic activity. These compounds are 2-tetralone-based unsymmetrical alpha, beta-unsaturated ketones with extended conjugation. The majority of the analogues were found to show moderate anti-cancer activity in in-vitro test systems against representative murine and human cancer cell lines. Evidence was obtained that these compounds display cytostatic activity against certain malignant cells and were well tolerated in mice. This study has also revealed various directions whereby the project may be augmented in the future with a view to finding compounds with increased cytotoxicity to neoplastic cells. C1 Acadia Univ, Dept Chem, Wolfville, NS B4P 2R6, Canada. Dalhousie Univ, Dept Chem, Halifax, NS, Canada. Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Jha, A (reprint author), Acadia Univ, Dept Chem, Wolfville, NS B4P 2R6, Canada. EM amitabh.jha@acadiau.ca RI Jha, Amitabh/B-5452-2010 OI Jha, Amitabh/0000-0002-6305-0721 NR 36 TC 17 Z9 17 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1808 EI 1875-628X J9 LETT DRUG DES DISCOV JI Lett. Drug Des. Discov. PD JUL PY 2006 VL 3 IS 5 BP 304 EP 310 DI 10.2174/157018006777574131 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 060BQ UT WOS:000238776700005 ER PT J AU Snyder, KM Mackall, CL Fry, TJ AF Snyder, Kristen M. Mackall, Crystal L. Fry, Terry J. TI IL-7 in allogeneic transplant: Clinical promise and potential pitfalls SO LEUKEMIA & LYMPHOMA LA English DT Review DE cytokines; stem cell transplant; immunotherapy; immune reconstitution ID BONE-MARROW-TRANSPLANTATION; CD8(+) T-CELLS; VERSUS-HOST-DISEASE; RHEUMATOID-ARTHRITIS; IN-VIVO; INTERLEUKIN-7 PRODUCTION; IMMUNE RECONSTITUTION; THYMIC EMIGRANTS; DEFICIENT MICE; GRAFT AB Much progress has been made in the field of allogeneic stem cell transplantation. However, one major barrier is the delay in immune recovery that can persist for months post-transplant and results in increased susceptibility to infection and relapse of malignancy. Strategies to improve immune recovery must be balanced with the potential for those therapies to exacerbate graft vs host disease. Interleukin 7 is a member of the gamma c cytokine family that is required for T-cell development and maintenance of naive T- cell populations. In addition, IL-7 plays a major role in the expansion of mature T-cells that occurs during lymphopenia and therapeutic IL-7 can enhance both quantitative and functional immune recovery following T-cell depletion. Thus, this agent holds much promise as an immunorestorative agent and as an adjuvant to vaccines or adoptive immunotherapy. Clinic trials with IL-7 are underway. Murine studies with IL-7 in the allogeneic transplant have demonstrated that the potent immune effects of this agent can also be achieved in this setting. However, these studies have indicated that the potential for IL-7 to worsen GVHD exists and that this effect may abrogate the immune benefits. Thus, careful consideration of how best to incorporate IL-7 into allogeneic trials will be needed if the full potential of this agent is to be realized. C1 NCI, Immunol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Fry, TJ (reprint author), Bldg 10,Room 1-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM fryt@mail.nih.gov NR 44 TC 18 Z9 19 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUL PY 2006 VL 47 IS 7 BP 1222 EP 1228 DI 10.1080/10428190600555876 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 075YD UT WOS:000239922600007 PM 16923550 ER PT J AU Cantor, D AF Cantor, David TI The frustrations of families: Henry Lynch, heredity, and cancer control, 1962-1975 SO MEDICAL HISTORY LA English DT Article; Proceedings Paper CT History of Medicine Division Brown Bag Seminar CY DEC 15, 2004 CL Natl Lib Med, Bethesda, MD HO Natl Lib Med ID NONPOLYPOSIS COLORECTAL-CANCER; MEDICAL GENETICS; LYNCH-SYNDROME; PSYCHODYNAMICS; CARCINOMA; HISTORY; BREAST C1 NCI, Div Ctr Prevent, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), NCI, Div Ctr Prevent, Execut Plaza N,Suite 2025, Bethesda, MD 20892 USA. EM cantord@mail.nih.gov NR 118 TC 10 Z9 10 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0025-7273 J9 MED HIST JI Med. Hist. PD JUL PY 2006 VL 50 IS 3 BP 279 EP 302 PG 24 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 068CT UT WOS:000239350300001 PM 16902702 ER PT J AU McKenzie, TL Catellier, DJ Conway, T Lytle, LA Grieser, M Webber, LA Pratt, CA Elder, JP AF McKenzie, Thomas L. Catellier, Diane J. Conway, Terry Lytle, Leslie A. Grieser, Mira Webber, Larry A. Pratt, Charlotte A. Elder, John P. TI Girls' activity levels and lesson contexts in middle school PE: TAAG baseline SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE children; exercise; females; intervention; physical; sports ID PHYSICAL-EDUCATION; INTERVENTION; ELEMENTARY; HEALTH; YOUTH; AGE AB Purpose: To assess girls' physical activity (PA) in middle school physical education (PE) as it relates to field site, lesson context and location, teacher gender, and class composition. Methods: We observed girls' PA levels, lesson contexts, and activity promotion by teachers in 431 lessons in 36 schools from six field sites participating in the Trial of Activity for Adolescent Girls. Interobserver reliabilities exceeded 90% for all three categories. Data were analyzed using mixed-model ANOVA with controls for clustering effects by field site and school. Results: Mean lesson length was 37.3 (+/- 9.4) min. Time (13.9 +/- 7.0 min) and proportion of lessons (37.9 +/- 18.5%) spent in moderate to vigorous PA (MVPA), and time (4.8 +/- 4.2 min) and proportion of lessons (13.1 +/- 11.7%) in vigorous PA (VPA) differed by field site (P < 0.004). Lesson time for instructional contexts differed by field site, with overall proportions as follows: game play (27.3%), management (26.1%), fitness activities (19.7%), skill drills (12.1%), knowledge (10.6%), and free play (4.4%). Coed classes were 7.9 min longer than girls-only classes (P = 0.03). Although 27 s shorter, outdoor lessons were more intense (MVPA% = 45.7 vs 33.7% of lesson, P < 0.001) and provided 4.0 more MVPA minutes (P < 0.001). MVPA, VPA, and lesson contexts did not differ by teacher gender. There was little direct promotion of PA by teachers during lessons. Conclusions: Substantial variation in the conduct of PE exists. Proportion of lesson time girls spent accruing MVPA (i.e., 37.9%) fell short of the Healthy People 2010 objective of 50%. Numerous possibilities exist for improving girls' PA in PE. C1 San Diego State Univ, Dept Exercise & Nutr Sci, San Diego, CA 92182 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Minneapolis, MN USA. Univ Maryland, College Pk, MD 20742 USA. Tulane Univ, New Orleans, LA 70118 USA. NHLBI, Bethesda, MD 20892 USA. RP McKenzie, TL (reprint author), San Diego State Univ, Dept Exercise & Nutr Sci, San Diego, CA 92182 USA. EM tmckenzie@sdsu.edu FU NHLBI NIH HHS [U01 HL066845, UO1HL066852, UO1HL066845, UO1HL066857, U01 HL066857, UO1HL066853, U01 HL066853, U01 HL066845-01, UO1HL066858, U01 HL066856, U01 HL066858, UO1HL066855, U01 HL066852, UO1HL066856, U01 HL066855] NR 27 TC 54 Z9 54 U1 0 U2 12 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 JUL PY 2006 VL 38 IS 7 BP 1229 EP 1235 DI 10.1249/01.mss.0000227307.34149.f3 PG 7 WC Sport Sciences SC Sport Sciences GA 062UU UT WOS:000238971100006 PM 16826019 ER PT J AU Bornstein, MH Gini, M Suwalsky, JTD Putnick, DL Haynes, OM AF Bornstein, Marc H. Gini, Motti Suwalsky, Joan T. D. Putnick, Diane L. Haynes, O. Maurice TI Emotional availability in mother-child dyads: Short-term stability and continuity from variable-centered and person-centered perspectives SO MERRILL-PALMER QUARTERLY-JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID INFANTS AB Emotional availability (EA) is a prominent index of socioemotional adaptation in the parent-child dyad. Can basic psychometric properties of EA be looked at from both variable (scale) and person (cluster) points of view in individuals and in dyads? Is EA stable and continuous over a short period of time? This methodological study shows significant short-term stability and continuity in EA as measured with individual and dyadic Emotional Availability Scales and in clusters of individuals and dyads on EA scores in 52 mothers and their 5-month-olds observed twice at home. This work documents psychometric properties of the emotional availability construct from both variable and person orientations. C1 NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Dept Hlth & Human Serv, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov RI Putnick, Diane/B-1707-2009; OI Putnick, Diane/0000-0002-6323-749X NR 50 TC 27 Z9 27 U1 3 U2 3 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0272-930X J9 MERRILL PALMER QUART JI Merrill-Palmer Q.-J. Dev. Psychol. PD JUL PY 2006 VL 52 IS 3 BP 547 EP 571 DI 10.1353/mpq.2006.0024 PG 25 WC Psychology, Developmental SC Psychology GA 099YI UT WOS:000241633300007 ER PT J AU Sood, R English, MA Jones, MP Mullikin, J Wang, DM Anderson, M Wu, DY Chandrasekharappa, SC Yu, J Zhang, JH Liu, PP AF Sood, Raman English, Milton A. Jones, MaryPat Mullikin, James Wang, Duen-Mei Anderson, Maria Wu, Dongying Chandrasekharappa, Settara C. Yu, Jun Zhang, Jinghui Liu, P. Paul TI Methods for reverse genetic screening in zebrafish by resequencing and TILLING SO METHODS LA English DT Article DE resequencing; TILLING; SNPdetector; zebrafish; ENU mutagenesis; testes cryopreservation ID INDUCED POINT MUTATIONS; CRYOPRESERVATION; TOOL; INACTIVATION; SPERMATOZOA; DISCOVERY AB Animal models provide an in vivo system to study gene function by transgenic and knockout approaches. Targeted knockout approaches have been very successful in mice, but are currently not feasible in zebrafish due to the inability to grow embryonic stem cells. As an alternative, a reverse genetic approach that utilizes screening by resequencing and/or TILLING (Targeting Induced Local Lesions IN Genomes) of mutagenized genomes has recently gained popularity in the zebrafish field. Spermatogonia of healthy males are mutagenized using ENU (N-ethyl-N-nitrosourea) and F1 progeny is collected by breeding treated males with healthy wild type females. Sperm and DNA banks are generated from F1 males. DNA is screened for ENU-induced mutations by sequencing or TILLING. These mutations can then be studied by in vitro fertilization (IVF) from the cryopreserved sperm of the corresponding F1 male followed by breeding to homozygosity. A high-throughput method of screening for rare heterozygotes and efficient recovery of mutant lines are important in identification of a large number of mutations using this approach. This article provides optimized protocols for resequencing and TILLING based on our experiences. We performed a pilot screen on 1235 F1 males by resequencing 54 exons from 17 genes and analyzed the sequencing data using multiple programs to maximize the mutation detection with minimal false positive detection. As an alternative to sequencing, we developed the protocols for TILLING by capillary electrophoresis using an ABI Genetic analyzer 3100 platform followed by fragment analysis using GeneScan and Genotyper softwares. PCR products generated by fluorescently labeled universal primers and tailed exon-specific primers were pooled 4-fold prior to heteroduplex formation. Overall, our pilot screen shows that a combination of TILLING and sequencing is optimal for achieving cost-effective, high-throughput screening of a large number of samples. Amplicons with fewer common SNPs are ideal for TILLING whereas amplicons with multiple SNPs and in/del polymorphisms are best suited for sequencing followed by analysis with SNPdetector. (c) 2006 Elsevier Inc. All rights reserved. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Chinese Acad Sci, Beijing Genom Inst, Beijing, Peoples R China. NCI, NIH, Bethesda, MD USA. RP Sood, R (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM rsood@mail.nih.gov RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU Intramural NIH HHS NR 28 TC 64 Z9 70 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 1046-2023 J9 METHODS JI Methods PD JUL PY 2006 VL 39 IS 3 BP 220 EP 227 DI 10.1016/j.ymeth.2006.04.012 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084AN UT WOS:000240504000007 PM 16828311 ER PT J AU Hooks, JJ Chin, MS Kumar, S Momma, Y Hooper, LC Nagineni, CN Chan, CC Detrick, B AF Hooks, John J. Chin, Marian S. Srinivasan, Kumar Momma, Yuko Hooper, Laura C. Nagineni, Chandrasekhararn N. Chan, Chi-Chao Detrick, Barbara TI Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway SO MICROBES AND INFECTION LA English DT Article DE cytomegalovirus (CMV); retinal pigment epithelial cells (RPE); COX-2; PGE ID GENE-EXPRESSION; INDUCTION; INFECTION; BETA; FIBROBLASTS; INVOLVEMENT; INHIBITION; ACTIVATION; VIRUS; E-2 AB Cytomegalovirus (CMV) retinitis is characterized by alterations in retinal cell function and host responses to virus replication. The goal of this study was to evaluate the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PGE) in CMV infected human retinal pigment epithelial (RPE) cells and to determine their effect on virus replication. CMV immediate early (IE) protein and COX-2 proteins were identified in RPE cells in retinal tissue sections from patients with CMV retinitis. COX-2 mRNA and protein were induced after CMV infection of human RPE cell cultures. CMV infection of RPE cells induced translocation of NF-kappa B from the cytoplasm to the nucleus. PGE(1) and PGE(2) were significantly (p < 0.001) increased in human RPE cell cultures infected with CMV. Inhibition of CMV IE gene by antisense oligonucleotides abrogated induction of mRNA for COX-2 and protein synthesis of COX-2 and PGE(2). PGE enhanced CMV plaque formation and real time PCR analysis revealed that PGE treatment significantly increased CMV DNA copy numbers. These studies demonstrate that when CMV replicates within human RPE cells, COX-2 induction augments virus replication via the PGE pathway. The induction of COX-2 and PGE during retinal CMV infection may augment virus replication and alter a variety of retinal physiological responses. Published by Elsevier SAS. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA. RP Hooks, JJ (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N248, Bethesda, MD 20892 USA. EM hooksj@nei.nih.gov FU Intramural NIH HHS NR 30 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2006 VL 8 IS 8 BP 2236 EP 2244 DI 10.1016/j.micinf.2006.04.010 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 092RN UT WOS:000241115100031 PM 16782382 ER PT J AU Giussani, P Maceyka, M Le Stunff, H Mikami, A Lepine, S Wang, E Kelly, S Merrill, AH Milstien, S Spiegel, S AF Giussani, P Maceyka, M Le Stunff, H Mikami, A Lepine, S Wang, E Kelly, S Merrill, AH Milstien, S Spiegel, S TI Sphingosine-1-phosphate phosphohydrolase regulates endoplasmic reticulurn-to-Golgi trafficking of ceramide SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SPHINGOSINE 1-PHOSPHATE; SPHINGOLIPID METABOLISM; SECRETORY PATHWAY; CELL-SURFACE; SACCHAROMYCES-CEREVISIAE; SPHINGOMYELIN SYNTHESIS; FAMILY-MEMBERS; ANIMAL-CELLS; RAT-LIVER; TRANSPORT AB Previous studies demonstrated that sphingosine-I-phosphate (SIP) phosphohydrolase I (SPP-1), which is located mainly in the endoplasmic reticulum (ER), regulates sphingolipid metabolism and apoptosis (H. Le Stunff et al., J. Cell Biol. 158:1039-1049, 2002). We show here that the treatment of SPP-1-overexpressing cells with SIP, but not with dihydro-SIP, increased all ceramide species, particularly the long-chain ceramides. This was not due to inhibition of ceramide metabolism to sphingomyelin or monohexosylceramides but rather to the inhibition of ER-to-Golgi trafficking, determined with the fluorescent ceramide analog N-(4,4-difluoro-5,7dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-D-erythro-sphingosine (DMB-Cer). Fumonisin III, an inhibitor of ceramide synthase, prevented S1P-induced elevation of all ceramide species and corrected the defect in ER transport of DMB-Cer, readily allowing its detection in the Golgi. In contrast, ceramide accumulation had no effect on either the trafficking or the metabolism of 6-([N-(7-nitrobenzo-2-oxa- 1,3-diazol-4-yl) amino] hexanoyl)-sphingosine, which rapidly labels the Golgi even at 4 degrees C. Protein trafficking from the ER to the Golgi, determined with vesicular stomatitis virus ts045 G protein fused to green fluorescent protein, was also inhibited in SPP-1-overexpressing cells in the presence of SIP but not in the presence of dihydro-S1P. Our results suggest that SPP-1 regulates ceramide levels in the ER and thus influences the anterograde membrane transport of both ceramide and proteins from the ER to the Golgi apparatus. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Massey Canc Ctr, Richmond, VA 23298 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. NIMH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, 1101 E Marshall St,Room 2-011 Sanger Hall, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Maceyka, Michael/B-9277-2008 FU NIGMS NIH HHS [GM069338, GM43880, R01 GM043880, R37 GM043880, U54 GM069338] NR 60 TC 31 Z9 31 U1 0 U2 4 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 JUL PY 2006 VL 26 IS 13 BP 5055 EP 5069 DI 10.1128/MCB.02107-05 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 056FT UT WOS:000238507800026 PM 16782891 ER PT J AU Stavreva, DA Kawasaki, M Dundr, M Koberna, K Muller, WG Tsujimura-Takahashi, T Komatsu, W Hayano, T Isobe, T Raska, I Misteli, T Takahashi, N McNally, JG AF Stavreva, DA Kawasaki, M Dundr, M Koberna, K Muller, WG Tsujimura-Takahashi, T Komatsu, W Hayano, T Isobe, T Raska, I Misteli, T Takahashi, N McNally, JG TI Potential roles for ubiquitin and the proteasome during ribosome biogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ARF TUMOR-SUPPRESSOR; RIBONUCLEOPROTEIN COMPLEXES; PROTEIN-DEGRADATION; NUCLEAR EXPORT; IN-VIVO; C-MYC; NUCLEOLUS; RNA; TRANSCRIPTION; CELLS AB We have investigated the possible involvement of the ubiquitin-proteasome system (UPS) in ribosome biogenesis. We find by immunofluorescence that ubiquitin is present within nucleoli and also demonstrate by immunoprecipitation that complexes associated with pre-rRNA processing factors are ubiquitinated. Using short proteasome inhibition treatments, we show by fluorescence microscopy that nucleolar morphology is disrupted for some but not all factors involved in ribosome biogenesis. Interference with proteasome degradation also induces the accumulation of 90S preribosomes, alters the dynamic properties of a number of processing factors, slows the release of mature rRNA from the nucleolus, and leads to the depletion of 18S and 28S rRNAs. Together, these results suggest that the UPS is probably involved at many steps during ribosome biogenesis, including the maturation of the 90S preribosome. C1 NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, Bethesda, MD 20892 USA. Charles Univ, Fac Med 1, Inst Cellular Biol & Pathol, Prague 12800 2, Czech Republic. Acad Sci Czech Republ, Inst Physiol, CR-12800 Prague, Czech Republic. Tokyo Univ Agr & Technol, Dept Appl Biol Sci, United Grad Sch Agr, Tokyo 1838509, Japan. Tokyo Univ Agr & Technol, Dept Biotechnol, United Grad Sch Agr, Tokyo 1838509, Japan. Integrated Proteom Syst Project, Pioneer Res Genome Frontier, Minist Educ Culture Sports Sci & Technol Japan, Tokyo 1838509, Japan. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, 41 Lib Dr, Bethesda, MD 20892 USA. EM ntakahas@cc.tuat.ac.jp; mcnallyj@exchange.nih.gov RI TAKAHASHI, Nobuhiro/G-1129-2013 FU Intramural NIH HHS NR 61 TC 69 Z9 71 U1 0 U2 4 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 JUL PY 2006 VL 26 IS 13 BP 5131 EP 5145 DI 10.1128/MCB.02227-05 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 056FT UT WOS:000238507800032 PM 16782897 ER PT J AU Coppola, V Barrick, CA Bobisse, S Rodriguez-Galan, MC Pivetta, M Reynolds, D Howard, OMZ Palko, ME Esteban, PF Young, HA Rosato, A Tessarollo, L AF Coppola, Vincenzo Barrick, Colleen A. Bobisse, Sara Rodriguez-Galan, Maria Cecilia Pivetta, Michela Reynolds, Della Howard, O. M. Zack Palko, Many Ellen Esteban, Pedro F. Young, Howard A. Rosato, Antonio Tessarollo, Lino TI The scaffold protein Cybr is required for cytokine-modulated trafficking of leukocytes in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTORS; LYMPHOCYTE; CYTOHESIN-1; ACTIVATION; MIGRATION; COMPLEX; LFA-1; MICE; CHEMOKINES; REGULATOR AB Trafficking and cell adhesion are key properties of cells of the immune system. However, the molecular pathways that control these cellular behaviors are still poorly understood. Cybr is a scaffold protein highly expressed in the hematopoietic/immune system whose physiological role is still unknown. In vitro studies have shown it regulates LFA-1, a crucial molecule in lymphocyte attachment and migration. Cybr also binds cytohesin-1, a guanine nucleotide exchange factor for the ARF GTPases, which affects actin cytoskeleton remodeling during cell migration. Here we show that expression of Cybr in vivo is differentially modulated by type 1 cytokines during lymphocyte maturation. In mice. Cybr deficiency negatively affects leukocytes circulating in blood and lymphocytes present in the lymph nodes. Moreover, in a Th1-polarized mouse model, lymphocyte trafficking is impaired by loss of Cybr, and Cybr-deficient mice with aseptic peritonitis have fewer cells than controls present in the peritoneal cavity, as well as fewer leukocytes leaving the bloodstream. Mutant mice injected with Moloney murine sarcoma/leukemia virus develop significantly larger tumors than wild-type mice and have reduced lymph node enlargement, suggesting reduced cytotoxic T-lymphocyte migration. Taken together, these data support a role for Cybr in leukocyte trafficking, especially in response to proinflammatory cytokines in stress conditions. C1 NCI, Mouse Canc Genet Program, Neural Dev Grp, Frederick, MD USA. NCI, Expt Immunol Lab, Frederick, MD USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD USA. Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. Ist Oncol Veneto, Padua, Italy. RP Tessarollo, L (reprint author), NCI, Mouse Canc Genet Program, Neural Dev Grp, Frederick, MD USA. EM tessarol@ncifcrf.gov RI Coppola, Vincenzo/E-2917-2011; Howard, O M Zack/B-6117-2012; Rosato, Antonio/E-8626-2010; OI Coppola, Vincenzo/0000-0001-6163-1779; Howard, O M Zack/0000-0002-0505-7052; Rosato, Antonio/0000-0002-5263-8386 FU Intramural NIH HHS NR 31 TC 13 Z9 14 U1 0 U2 1 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 JUL PY 2006 VL 26 IS 14 BP 5249 EP 5258 DI 10.1128/MCB.02473-05 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 062AZ UT WOS:000238918000005 PM 16809763 ER PT J AU Lee, RJ AF Lee, Robert J. TI Liposomal delivery as a mechanism to enhance synergism between anticancer drugs SO MOLECULAR CANCER THERAPEUTICS LA English DT Editorial Material ID DOXORUBICIN; TUMORS C1 Ohio State Univ, Coll Pharm, Div Pharmaceut, Natl Sci Fdn,Nanoscale Sci & Engn Ctr, Columbus, OH 43210 USA. Ohio State Univ, NCI, Inst Comprehens Canc Ctr, Columbus, OH 43210 USA. RP Lee, RJ (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, Natl Sci Fdn,Nanoscale Sci & Engn Ctr, 500 W 12th Ave, Columbus, OH 43210 USA. EM lee.1339@osu.edu NR 11 TC 16 Z9 17 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2006 VL 5 IS 7 BP 1639 EP 1640 DI 10.1158/1535-7163.MCT-06-CO2 PG 2 WC Oncology SC Oncology GA 072OO UT WOS:000239682900001 PM 16891448 ER PT J AU Zhang, Q Yang, XMJ Kundu, SD Pins, M Javonovic, B Meyer, R Kim, SJ Greenberg, NM Kuzel, T Meagher, R Guo, YL Lee, C AF Zhang, Qiang Yang, Ximing J. Kundu, Shilajit D. Pins, Michael Javonovic, Borko Meyer, Robert Kim, Seong-Jin Greenberg, Norman M. Kuzel, Timothy Meagher, Richard Guo, Yinglu Lee, Chung TI Blockade of transforming growth factor-beta signaling in tumor-reactive CD8(+) T cells activates the antitumor immune response cycle SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROSTATE-CANCER CELLS; GENE-THERAPY; INFLAMMATORY DISEASE; ADOPTIVE TRANSFER; INTERFERON-BETA; BCL-2 FAMILY; MICE CAUSES; SUPPRESSION; METASTASIS; ANGIOGENESIS AB Transforming growth factor-beta (TGF-beta) is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells leads to evasion of host immune surveillance and tumor progression. Results of our early studies showed that adoptive transfer of tumor-reactive, TGF-beta-insensitive CD8(+) T cells into immunocompetent mice was able to eradicate lung metastasis of mouse prostate cancer. The present study was conducted with three objectives. (a) We tested if this technology could be applied to the treatment of solid xenograft tumors in allogeneic immunodeficient hosts. (b) We determined relevant variables in the tumor microenvironment with the treatment. (c) We tested if immune cells other than CD8(+) T cells were required for the antitumor effect. Mouse prostate cancer cells, TRAMP-C2 of the C57BL/6 strain, grown in immunodeficient allogeneic hosts of BALB/c strain, were used as a xenograft model. Tumor-reactive CD8+ T cells from C57BL/6 mice were isolated, expanded ex vivo, and rendered insensitive to TGF-beta by introducing a dominant-negative TGF-beta type 11 receptor vector. Seven days following s.c. injection of TRAMP-C2 cells (5 x 10(5)) into the flank of male BALB/c-Rag1(-/-) mice, tumor-reactive, TGF-beta-insensitive CD8(+) T cells (1.5 x 10(7)) were transferred with and without the cotransfer of an equal number of CD8-depleted splenocytes from C57BL/6 donors. Naive CD8(+) T cells or green fluorescent protein-empty vectortransfected tumor-reactive CD8(+) T cells were transferred as controls. Forty days following the transfer, the average tumor weight in animals that received cotransfer of tumor-reactive, TGF-beta-insensitive CD8(+) T cells and CDEI-depleted splenocytes was at least 50% less than that in animals of all other groups (P < 0.05). Tumors in animals of the former group showed a massive infiltration of CD8+ T cells. This was associated with secretion of relevant cytokines, decreased tumor proliferation, reduced angiogenesis, and increased tumor apoptosis. Based on these results, we postulated a concept of antitumor immune response cycle in tumor immunology. C1 Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Peking Univ, Inst Urol, Hosp 1, Beijing 100871, Peoples R China. RP Lee, C (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 303 E Chicago Ave,Tarry 16-733, Chicago, IL 60611 USA. EM c-lee7@northwestern.edu FU NCI NIH HHS [CA107186] NR 42 TC 25 Z9 28 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2006 VL 5 IS 7 BP 1733 EP 1743 DI 10.1158/1535-7163.MCT-06-0109 PG 11 WC Oncology SC Oncology GA 072OO UT WOS:000239682900012 PM 16891459 ER PT J AU Jin, YS Iwata, KK Belldegrun, A Figlin, R Pantuck, A Zhang, ZF Lieberman, R Rao, JY AF Jin, Yusheng Iwata, Kenneth K. Belldegrun, Arie Figlin, Robert Pantuck, Allan Zhang, Zuo-Feng Lieberman, Ronald Rao, Jianyu TI Effect of an epidermal growth factor receptor tyrosine kinase inhibitor on actin remodeling in an in vitro bladder cancer carcinogenesis model SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; MESENCHYMAL TRANSITION; TUMOR PROGRESSION; BINDING PROTEINS; CDC42 GTPASES; LUNG-CANCER; TRANSFORMATION; CYTOSKELETAL; BIOMARKER; RAC AB Alteration of actin remodeling is a marker of malignant-associated field defect and a potential surrogate biomarker for chernoprevention trials. We tested erlotinib, a specific tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), on actin remodeling in a bladder carcinogenic model consisting of untransformed HUC-PC cells and transformed MC-T11 cells, both derived from the same normal human urothelial clone immortalized by SV40. Erlotinib had a selective growth inhibitory and actin remodeling effect on MC-T11 cells over HUC-PC cells, as examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide assay and immunofluorescence labeling with laser scan cytometer analysis, respectively. The IC50 of untransformed HUC-PC cells was significantly higher than that of transformed MC-T11 cells (P < 0.05, t test). The actin remodeling effect was more prominent at lower dosage levels (1/8-1/4 of IC50), which was accompanied by an increased cell adhesion and decreased motility. At higher dosage levels (1/2 of IC50), erlotinib induced a decreased adhesion and anoikis (detachment-associated apoptosis). The transformed MC-T11, but not HUC-PC, showed a weak constitutive EGFR phosphorylation activity, which was inhibited by erlotinib in a closeresponse manner. However, on epidermal growth factor stimulation, both cell lines showed a similar dose-response inhibitory effect on phosphorylated EGFR and mitogen-activated protein kinase (MAPK; P44/P42) activities, and MAPK inhibitor PD98059 showed no specific effect on erlotinib-induced actin remodeling, suggesting that pathways other than MAPK (P44/P42) may be responsible for erlotinib-induced actin remodeling. The findings provide evidence to support erlotinib-based bladder cancer chemo-prevention and using actin remodeling as a marker for erlotinib-based intervention trials. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA 90095 USA. OSI Pharmaceut Inc, New York, NY USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Rao, JY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Box 951732, Los Angeles, CA 90095 USA. EM jrao@mednet.ucla.edu FU NCI NIH HHS [U01CA96116] NR 44 TC 9 Z9 9 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 JUL PY 2006 VL 5 IS 7 BP 1754 EP 1763 DI 10.1158/1535-7163.MCT-06-0043 PG 10 WC Oncology SC Oncology GA 072OO UT WOS:000239682900014 PM 16891461 ER PT J AU Schmitt, M Walker, MP Richards, RG Bocchinfuso, WP Fukuda, T Medina, D Kittrel, FS Korach, KS DiAugustine, RP AF Schmitt, M. Walker, M. P. Richards, R. G. Bocchinfuso, W. P. Fukuda, T. Medina, D. Kittrel, F. S. Korach, K. S. DiAugustine, R. P. TI Expression of heregulin by mouse mammary tumor cells: Role in activation of ErbB receptors SO MOLECULAR CARCINOGENESIS LA English DT Article DE tyrosine phosphorylation; proteolytic cleavage; proliferation ID EPIDERMAL-GROWTH-FACTOR; NEU-DIFFERENTIATION FACTOR; BREAST-CANCER CELLS; TRANSGENIC MICE; EPITHELIAL-CELLS; TYROSINE KINASE; DRUG-RESISTANCE; CARCINOMA CELLS; MESSENGER-RNA; IN-VIVO AB The inappropriate activation of one or more members of the ErbB family of receptor tyrosine kinases [ErbB-1 (EGFR), ErbB-2, ErbB-3, ErbB-4] has been linked with oncogenesis. ErbB-2 is frequently coexpressed with ErbB-3 in breast cancer. cells and in the presence of the ligand heregulin (HRG) the ErbB-2/ErbB-3 receptors form a signaling heterodimer that can affect cell proliferation and apoptosis. The major goal of the present study was to determine whether endogenous HRG causes autocrine/paracrine activation of ErbB-2/ErbB-3 and contributes to the proliferation of mammary epithelial tumor cells. Tyrosine-phosphorylated (activated) ErbB-2 and ErbB-3 receptors were detected in the majority of extracts from tumors that had formed spontaneously or as a result of oncogene expression. HRG-1 transcripts and protein were found in the epithelial cells of most of these mouse mammary tumors. Various mouse mammary cell lines also contained activated ErbB-2/ErbB-3 and HRG transcripts. A similar to 50 kDa C-terminal fragment of pro-HRG was detected, which indicates that the HRG-1 precursor is readily processed by these cells. It is likely that the secreted mature HRG activated the ErbB-2/3 receptors. Addition of an antiserum against HRG to the mammary epithelial tumor cell line TM-6 reduced ErbB-3 Tyr-phosphorylation. Treatment with HRG-1 siRNA oligonucleoticles or infection with a retroviral construct to stably express HRG siRNA effectively reduced HRG protein levels, ErbB-2/ErbB-3 activation, and the rate of proliferation, which could be reversed by the addition of HRG. The cumulative findings from these experiments show that coexpression of the HRG ligand contributes to activation of ErbB-2/Erb-3 in mouse mammary tumor cells in an autocrine or paracrine fashion. Published 2006 Wiley-Liss, Inc. C1 NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP DiAugustine, RP (reprint author), NIEHS, NIH, Mol Carcinogenesis Lab, Mail Drop D4-04,POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 59 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 2006 VL 45 IS 7 BP 490 EP 505 DI 10.1002/mc.20180 PG 16 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 060MW UT WOS:000238807300003 PM 16482517 ER PT J AU Benavides, F Gomez, G Venables-Griffith, A Lambertz, I Flores, M Angel, JM Fuchs-Young, R Richie, ER Conti, CJ AF Benavides, Fernando Gomez, Gregorio Venables-Griffith, Ann Lambertz, Isabel Flores, Monica Angel, Joe M. Fuchs-Young, Robin Richie, Ellen R. Conti, Claudio J. TI Differential susceptibility to chemically induced thymic lymphomas in SENCARB and SSIN inbred mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE SENCARB/Pt; SSIN/Sprd; MNU; DMBA; thymic lymphoma ID METHYL-N-NITROSOUREA; COLON-CANCER SUSCEPTIBILITY; MURINE LEUKEMIA PROVIRUSES; SQUAMOUS-CELL CARCINOMAS; SKIN TUMOR PROGRESSION; MOUSE SKIN; AKR/J MICE; STRAINS; LOCUS; CARCINOGENESIS AB In the past 20 yr, several inbred strains have been derived from SENCAR outbred mice. These strains display different susceptibility to the induction of papillomas and progression to squamous cell carcinomas (SCC) in the skin after chemical carcinogenesis. In the present study, we showed that one of these strains SENCARB/Pt was highly susceptible to the development of N-methyl-N-nitrosourea (MNU)- and 7,12-dimethylbenz[a]anthracene (DMBA)-induced lymphomas. In contrast, the SSIN/Sprd inbred strain is completely resistant to T-cell lymphomagenesis by both carcinogens. Within 175 d after a single injection of 75 mg/kilogram body weight (kbw) of MNU, SENCARB/Pt mice exhibited a 91.6% incidence of lymphoma. In addition, during an independent tumorigenesis study with repeated doses of intragastric DMBA, SENCARB/Pt mice showed an incidence of 75% lymphoma development 300 d after the last treatment. Histopathological and flow cytometric parameters indicated that the lymphomas were of the T-cell lineage. In order to study the genetics of MNU-induced tumorigenesis, we generated F1 hybrid mice between SSIN/Sprd and SENCARB/Pt mice. Tumor incidence in MNU-injected F1 mice suggested that the high tumor incidence is a dominant trait. Loss of heterozygosity (LOH) analysis in these tumor samples revealed allelic imbalances on chromosomes 15 and 19. Given that these inbred strains are closely related, it is likely that a relatively small number of loci are responsible for the observed differences in susceptibility. Therefore, these SENCAR inbred strains constitute important new tools to study the genetic basis of resistance and susceptibility to chemically induced thymic lymphoma formation. (c) 2006 Wiley-Liss, Inc. C1 Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, Smithville, TX 78957 USA. NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Benavides, F (reprint author), Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, 1808 Pk Rd 1C,POB 389, Smithville, TX 78957 USA. RI Benavides, Fernando/E-7872-2011; Griffith, Ann/N-5624-2016 OI Griffith, Ann/0000-0001-5345-0222 FU NCI NIH HHS [CA16672, CA90922]; NIEHS NIH HHS [ES007784] NR 37 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 2006 VL 45 IS 7 BP 543 EP 548 DI 10.1002/mc.20182 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 060MW UT WOS:000238807300008 PM 16479612 ER PT J AU Zhang, ZP Chen, K Shih, JC Teng, CT AF Zhang, ZP Chen, K Shih, JC Teng, CT TI Estrogen-related receptors-stimulated monoamine oxidase B promoter activity is down-regulated by estrogen receptors SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ALPHA ERR-ALPHA; PROLIFERATOR-ACTIVATED RECEPTOR; INDEPENDENT TRANSCRIPTIONAL ACTIVATION; ELEMENT-DEPENDENT REGULATION; HORMONE RESPONSE ELEMENT; ORPHAN NUCLEAR RECEPTORS; HUMAN LACTOFERRIN GENE; GAMMA; EXPRESSION; COACTIVATOR AB Although there are studies published about the neuroprotective effect of estrogen, little is known about the mechanisms and cellular targets of the hormone. Recent reports demonstrate that estrogen down-regulates the expression of monoamine oxidase A and B (MAO-A and MAO-B) in the hypothalamus of the Macaques monkey, both of which are key isoenzymes in the neurotransmitter degradation pathway. Additionally, estrogen-related receptor alpha(ERR alpha) up-regulates MAO-B gene expression in breast cancer cells. ERR alpha recognizes a variety of estrogen response elements and shares many target genes and coactivators with estrogen receptor alpha (ER alpha). In this study, we investigate the interplay of ERs and ERRs in the regulation of MAO-B promoter activity. We demonstrate that ERR alpha and ERR alpha up-regulate MAO-B gene activity, whereas ER alpha and ER beta decrease stimulation in both a ligand-dependent and -independent manner. Ectopically expressed ERR alpha and ERR beta stimulate the expression of MAO- B mRNA and protein as well as increase the MAO-B enzymatic activity in ER-negative HeLa cells. The ability of ERRs to stimulate MAO-B promoter activity was reduced in ER-positive MCF-7 and T47D cells. Several AGGTCA motifs of the MAO- B promoter are responsible for up-regulation by ERRs. Interestingly, ER alpha or ER beta alone have no effect on MAO-B promoter activity but can down-regulate the activation function of ERRs, whereas glucocorticoid receptor does not. By using chromatin immunoprecipitation assay, we demonstrate that ERs compete with ERRs for binding to the MAO-B promoter at selective AGGTCA motifs, thereby changing the chromatin status and cofactor recruitment to a repressed state. These studies provide new insight into the relationship between ER alpha, ER beta, ERR gamma, and ERR gamma in modulation of MAO-B gene activity. C1 NIEHS, Head Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. RP Teng, CT (reprint author), NIEHS, Head Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233,MD E2-01, Res Triangle Pk, NC 27709 USA. EM teng1@niehs.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [R01 MH67968, R37 MH39085] NR 78 TC 33 Z9 34 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 JUL PY 2006 VL 20 IS 7 BP 1547 EP 1561 DI 10.1210/me.2005-0252 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 057CQ UT WOS:000238573300007 PM 16484337 ER PT J AU Parle-McDermott, A Mills, JL Molloy, AM Carroll, N Kirke, PN Cox, C Conley, MR Pangilinan, FJ Brody, LC Scott, JM AF Parle-McDermott, Anne Mills, James L. Molloy, Anne M. Carroll, Nicola Kirke, Peadar N. Cox, Christopher Conley, Mary R. Pangilinan, Faith J. Brody, Lawrence C. Scott, John M. TI The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE MTHFR; folate; nutrition; genetics; cancer; polymorphism; RCF; homocysteine; vitamin B-12 ID NEURAL-TUBE DEFECTS; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; RISK-FACTOR; LINKAGE DISEQUILIBRIUM; COLORECTAL NEOPLASIA; PLASMA HOMOCYSTEINE; COMMON MUTATION; SPINA-BIFIDA; COLON-CANCER; POLYMORPHISMS AB Individuals homozygous for the thermolabile variant (677TT) of methylenetetrahydrofolate reductase exhibit reduced folate status as evidenced by a drop in the biomarker red cell folate (RCF) compared to those who carry at least one 677C allele. We now report that a different polymorphism in the same enzyme, namely 1298A > C, is associated with increased RCF levels. Thus, these two common polymorphisms change a metabolic phenotype in opposite directions suggesting that their cancer protective associations are by different mechanisms. Published by Elsevier Inc. C1 NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. RP Brody, LC (reprint author), NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bldg 50,Room 5306,50 South Dr, Bethesda, MD 20892 USA. EM lbrody@helix.nih.gov FU Intramural NIH HHS NR 27 TC 29 Z9 30 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUL PY 2006 VL 88 IS 3 BP 290 EP 294 DI 10.1016/j.ymgme.2006.02.001 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 071QE UT WOS:000239615900012 PM 16621645 ER PT J AU Paulsson, J Chattoraj, DK AF Paulsson, J Chattoraj, DK TI Origin inactivation in bacterial DNA replication control SO MOLECULAR MICROBIOLOGY LA English DT Review ID COPY-NUMBER CONTROL; ESCHERICHIA-COLI MINICHROMOSOMES; P1 PLASMID REPLICATION; CHROMOSOME-REPLICATION; INITIATOR PROTEIN; BACILLUS-SUBTILIS; GENE-REGULATION; REPLICON; CELLS; HYPERINITIATION AB Initiation of DNA replication is a highly regulated process in all organisms. Proteins that are required to recruit DNA polymerase - initiator proteins - are often used to regulate the timing or frequency of initiation in the cell cycle by limiting either their own synthesis or availability. Studies of the Escherichia coli chromosome and of bacterial plasmids with iterated initiator binding sites (iterons) have revealed that, in addition to initiator limitation, replication origin inactivation is used to prevent replication that is untimely or excessive. Our recent studies of plasmid P1 revealed that this additional mode of control becomes a requirement when initiator availability is limited only by autoregulation. Thus, although initiator limitation appears to be a well-conserved and central mode of replication control, optimal replication might require additional control mechanisms. This review gives examples of how the multiple mechanisms can act synergistically, antagonistically or be partially redundant to guarantee low frequency events. The lessons learned are likely to help understand many other regulatory systems in the bacterial cell. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Univ Cambridge, Dept Appl Math & Theoret Phys, Cambridge CB3 0WA, England. NCI, Lab Biochem, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM chattord@mail.nih.gov NR 48 TC 27 Z9 27 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2006 VL 61 IS 1 BP 9 EP 15 DI 10.1111/j.1365-2958.2006.05229.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 054CI UT WOS:000238353300003 PM 16824091 ER PT J AU Nielsen, HJ Li, YF Youngren, B Hansen, FG Austin, S AF Nielsen, HJ Li, YF Youngren, B Hansen, FG Austin, S TI Progressive segregation of the Escherichia coli chromosome SO MOLECULAR MICROBIOLOGY LA English DT Article ID DNA-REPLICATION; CELL-DIVISION; LOCALIZATION; MOVEMENT; TERMINUS; PROTEIN; FTSK; ORGANIZATION; INITIATION; REPLISOME AB We have followed the fate of 14 different loci around the Escherichia coli chromosome in living cells at slow growth rate using a highly efficient labelling system and automated measurements. Loci are segregated as they are replicated, but with a marked delay. Most markers segregate in a smooth temporal progression from origin to terminus. Thus, the overall pattern is one of continuous segregation during replication and is not consistent with recently published models invoking extensive sister chromosome cohesion followed by simultaneous segregation of the bulk of the chromosome. The terminus, and a region immediately clockwise from the origin, are exceptions to the overall pattern and are subjected to a more extensive delay prior to segregation. The origin region and nearby loci are replicated and segregated from the cell centre, later markers from the various positions where they lie in the nucleoid, and the terminus region from the cell centre. Segregation appears to leave one copy of each locus in place, and rapidly transport the other to the other side of the cell centre. C1 Tech Univ Denmark, BioCentrum, DK-2800 Lyngby, Denmark. Natl Canc Inst, Gene Regulat & Chromosome Biol Lab, CCR, Ft Detrick, MD 21702 USA. RP Hansen, FG (reprint author), Tech Univ Denmark, BioCentrum, DK-2800 Lyngby, Denmark. EM fgh@biocentrum.dtu.dk NR 34 TC 97 Z9 97 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2006 VL 61 IS 2 BP 383 EP 393 DI 10.1111/j.1365-2958.2006.05245.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 057UY UT WOS:000238621900011 PM 16771843 ER PT J AU Paugh, SW Cassidy, MP He, HJ Milstien, S Sim-Selley, LJ Spiegel, S Selley, DE AF Paugh, SW Cassidy, MP He, HJ Milstien, S Sim-Selley, LJ Spiegel, S Selley, DE TI Sphingosine and its analog, the immunosuppressant 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol, interact with the CB1 cannabinoid receptor SO MOLECULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on the Cannabinoids CY JUN 24-27, 2005 CL Burlington, VT SP Int Cannabinoids Res Soc ID MICE DEFICIENT; FTY720; 1-PHOSPHATE; SPHINGOSINE-1-PHOSPHATE; BINDING; CELLS; RATS; TRANSPLANTATION; PHARMACOLOGY; STIMULATION AB Sphingosine-1-phosphate (S1P) and cannabinoid receptors are G-protein-coupled receptors that mediate the effects of S1P and endocannabinoids, respectively. Cannabinoid receptors also mediate the effects of Delta(9)-tetrahydrocannabinol, the primary psychoactive ingredient in marijuana, whereas S1P receptors contribute to the immunosuppressant effects of 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720). FTY720 is a sphingosine analog that can prevent renal graft rejections and suppress a variety of autoimmune disorders in animal models and clinical trials. We now report that both FTY720 and sphingosine interact with CB 1 but not CB 2 cannabinoid receptors. FTY720 and sphingosine inhibited the binding of the CB1-selective antagonist [H-3] N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide ([H-3] SR141716A) and the cannabinoid agonist [H-3](-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans4-(3-hydroxypropyl) cyclohexanol ([H-3]CP55,940) in a concentration-dependent manner in both CB1-expressing cell lines and mouse cerebellum. However, these compounds did not significantly alter [ 3H] CP55,940 binding to CB 2 receptors. In G-protein activation assays, FTY720 and sphingosine inhibited the maximal stimulation of guanosine 5'-O-(3-[S-35] thio) triphosphate binding by the cannabinoid agonist R-(+)-[2,3-dihydro-5-methyl-3-[( morpholinyl) methyl] pyrrolo[ 1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55,212-2) in a concentration-dependent manner, and this antagonist effect was not mimicked by S1P. FTY720 and sphingosine also inhibited activation of extracellular signal-regulated kinases 1 and 2 and Akt by WIN55,212-2 in intact Chinese hamster ovary (CHO) cells expressing CB1 receptors and attenuated WIN55,212-2-stimulated internalization of a fluorescence-tagged CB1 receptor in CHO cells. Moreover, both FTY720 and sphingosine produced rightward shifts in the concentration-effect curves of cannabinoid agonists for G-protein activation, indicating that they act as competitive CB1 antagonists. These results suggest that the CB1 receptor could be a novel target of FTY720 and that sphingosine could be an endogenous CB1 antagonist. C1 Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Sch Med, Inst Drug & Alcohol Studies, Richmond, VA 23298 USA. NIMH, Lab Celllular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Selley, DE (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, 1112 E Clay St,Box 980524, Richmond, VA 23298 USA. EM deselley@vcu.edu RI Paugh, Steven/A-7739-2008 OI Paugh, Steven/0000-0001-5697-9228 FU NCI NIH HHS [P30-CA16059]; NIDA NIH HHS [DA14277, DA05274]; NIGMS NIH HHS [GM43880] NR 37 TC 38 Z9 40 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 JUL PY 2006 VL 70 IS 1 BP 41 EP 50 DI 10.1124/mol.105.020552 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 055GL UT WOS:000238438100007 PM 16571654 ER PT J AU Partridge, JG Puhl, HL Ikeda, SR AF Partridge, JG Puhl, HL Ikeda, SR TI Phosducin and phosducin-like protein attenuate G-protein-coupled receptor-mediated inhibition of voltage-gated calcium channels in rat sympathetic neurons SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-GAMMA-SUBUNITS; CA2+ CHANNELS; REGULATOR PHOSDUCIN; BINDING; COMPLEX; CELLS; PHOSPHORYLATION; VISUALIZATION; TRANSLOCATION; SPECIFICITY AB Phosducin (PDC) has been shown in structural and biochemical experiments to bind the G beta gamma subunit of heterotrimeric G-proteins. A proposed function of PDC and phosducin-like protein ( PDCL) is the sequestration of "free" G beta gamma from the plasma membrane, thereby terminating signaling by G beta gamma. The functional impact of heterologously expressed PDC and PDCL on N-type calcium channel (Ca(V)2.2) modulation was examined in sympathetic neurons, isolated from rat superior cervical ganglia, using whole-cell voltage clamp. Expression of PDC and PDCL attenuated voltage-dependent inhibition of N-type calcium channels, a G beta gamma-dependent process, in a time-dependent fashion. Calcium current inhibition after short-term exposure to norepinephrine was minimally altered by PDC or PDCL expression. However, in the continued presence of norepinephrine, PDC or PDCL relieved calcium channel inhibition compared with control neurons. We observed similar results after activation of heterologously expressed metabotropic glutamate receptors with 100 mu M L-glutamate. Neurons expressing PDC or PDCL maintained suppression of inhibition after re-exposure to agonist. Unlike other G beta gamma sequestering proteins that abolish the short-term inhibition of Ca2+ channels, PDC and PDCL require prolonged agonist exposure before effects on modulation are realized. C1 NIAAA, Lab Mol Physiol, Sect Transmitter Siganling, NIH,DICBR, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, Sect Transmitter Siganling, NIH,DICBR, 5625 Fishers Lane,Room TS11A,MSC 9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508; Puhl, Henry/0000-0003-3095-7201 FU Intramural NIH HHS NR 38 TC 6 Z9 6 U1 0 U2 0 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 JUL PY 2006 VL 70 IS 1 BP 90 EP 100 DI 10.1124/mol.105.021394 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 055GL UT WOS:000238438100012 PM 16608918 ER PT J AU Liao, ZY Thibaut, L Jobson, A Pommier, Y AF Liao, ZY Thibaut, L Jobson, A Pommier, Y TI Inhibition of human tyrosyl-DNA phosphodiesterase by aminoglycoside antibiotics and ribosome inhibitors SO MOLECULAR PHARMACOLOGY LA English DT Article ID I COVALENT COMPLEXES; TOPOISOMERASE-I; SPINOCEREBELLAR ATAXIA; PHOSPHOLIPASE-D; HUMAN-CELLS; TDP1; REPAIR; DAMAGE; CAMPTOTHECIN; ENZYME AB DNA topoisomerase I (Top1) is the target of camptothecin, and novel Top1 inhibitors are in development as anticancer agents. Top1 inhibitors damage DNA by trapping covalent complexes between the Top1 catalytic tyrosine and the 3'-end of the broken DNA. Tyrosyl-DNA phosphodiesterase (Tdp1) can repair Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. Inhibiting Tdp1 has the potential to enhance the anticancer activity of Top1 inhibitors (http://discover.nci.nih. gov/pommier/pommier.htm) and to act as antiproliferative agents. In the present study, we report that neomycin inhibits Tdp1 more effectively than the related aminoglycosides paromomycin and lividomycin A. Inhibition of Tdp1 by neomycin is observed both with single- and double-stranded substrates but is slightly stronger with duplex DNA, which is different from aclarubicin, which only inhibits Tdp1 with the double-stranded substrate. Inhibition by neomycin can be overcome with excess Tdp1 and is greatest at low pH. To our knowledge, aminoglycoside antibiotics and the ribosome inhibitors thiostrepton, clindamycin-2-phosphate, and puromycin are the first reported pharmacological Tdp1 inhibitors. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS NR 40 TC 34 Z9 35 U1 1 U2 5 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 JUL PY 2006 VL 70 IS 1 BP 366 EP 372 DI 10.1124/mol.105.021865 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 055GL UT WOS:000238438100040 PM 16618796 ER PT J AU Opazo, JC Wildman, DE Prychitko, T Johnson, RM Goodman, M AF Opazo, Juan C. Wildman, Derek E. Prychitko, Tom Johnson, Robert M. Goodman, Morris TI Phylogenetic relationships and divergence times among New World monkeys (Platyrrhini, Primates) SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article DE New World monkeys; phylogeny; divergence times; South America ID BETA(2)-MICROGLOBULIN DNA-SEQUENCES; EPSILON-GLOBIN GENE; MOLECULAR PHYLOGENY; FOSSIL PLATYRRHINES; EVOLUTION; SYSTEMATICS; ARGENTINA; SUPPORT; LOCUS AB Orthologous sequences of six nuclear genes were obtained for all recognized genera of New World monkeys (Primates: Platyrrhini) and outgroups to evaluate the phylogenetic relationships and to estimate divergence times. Phylogenetic relationships were reconstructed by maximum parsimony, maximum likelihood, and Bayesian approaches. All methods resolved with 100% branch support genus-level relationships, except for the grouping of Aotus as a sister taxa of Cebus and Saimiri, which was supported by low bootstrap percentages and posterior probability. All approaches depict three monophyletic New World monkey families: Atelidae, Cebidae, and Pitheciidae; also within each family, all approaches depict the same branching topology. However, the approaches differ in depicting the relationships of the three families to one another. Maximum parsimony depicts the Atelidae and Cebidae as sister families next joined by the Pitheciidae. Conversely, likelihood and Bayesian phylogenetic trees group families Atelidae and Pitheciidae together to the exclusion of Cebidae. Divergence time estimations using both local molecular clock and Bayesian approaches suggest the families diverged from one another over a short period of geological time in the late Oligocene-early Miocene. (c) 2005 Elsevier Inc. All rights reserved. C1 Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Serv Support Perinatol Res Branch, NIH, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. RP Goodman, M (reprint author), Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. EM mgoodwayne@aol.com RI Opazo, Juan/A-9363-2009; OI Opazo, Juan/0000-0001-7938-4083 FU NIDDK NIH HHS [R01 DK56927] NR 38 TC 110 Z9 113 U1 4 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD JUL PY 2006 VL 40 IS 1 BP 274 EP 280 DI 10.1016/j.ympev.2005.11.015 PG 7 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 060MG UT WOS:000238805700024 PM 16698289 ER PT J AU Chen, HL Zhang, SMM Schwarzschild, MA Hernan, MA Ascherio, A AF Chen, Honglei Zhang, Shumin M. Schwarzschild, Michael A. Hernan, Miguel A. Ascherio, Alberto TI Survival of Parkinson's disease patients in a large prospective cohort of male health professionals SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; morality; survival; smoking; disease duration ID CIGARETTE-SMOKING; OLMSTED COUNTY; FOLLOW-UP; MORTALITY; PROGRESSION; RISK; NICOTINE; ONSET; DEATH; TIME AB Parkinson's disease (PD) patients have higher mortality than individuals without PD. However, most of the previous studies were based on prevalent cases and few examined the potential effects of duration and smoking on the survival of PD patients. We compared the survival experience of 288 men with incident PD diagnosed between 1986 and 2000 with that of 51,012 men free of PD in the Health Professionals Follow-up Study. As of January 2002, 92 deaths occurred among PD cases and 8,485 among men without PD. After controlling for age, men with PD had 60% higher mortality than those without PD (95% Cl: 1.3-2.0). PD mortality was strongly related to disease duration: compared with men without PD, the age-adjusted relative risk for PD patients was 1.1 during the first 5 years from diagnosis, 2.3 from 5 to 10 years, and 3.5 after 10 years (P < 0.0001 for trend). As expected, cigarette smoking was strongly and positively associated with total mortality among men free of PD (comparing >30 pack-years vs. never smokers, relative risk, 2.0; P < 0.0001 for trend), but this association was not observed among PD patients (RR: 1.0; P = 0.95 for trend). This study confirms that PD patients have a higher mortality than individuals without PD and that the excess mortality increases with disease duration. However, smoking seems to impose little additional risk among PD patients in this large cohort of health professionals. (C) 2006 Movement Disorder Society. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,Bldg Rall 101 Room A362,111 WT Al, Res Triangle Pk, NC 27709 USA. EM Chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS; NCI NIH HHS [CA55075]; NINDS NIH HHS [NS048468, NS35624] NR 29 TC 42 Z9 43 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2006 VL 21 IS 7 BP 1002 EP 1007 DI 10.1002/mds.20881 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 067EW UT WOS:000239285600019 PM 16602107 ER PT J AU Fidani, L Kalinderi, K Bostantjopoulou, S Clarimon, J Goulas, A Katsarou, Z Hardy, J Kotsis, A AF Fidani, Liana Kalinderi, Kallirhoe Bostantjopoulou, Sevasti Clarimon, Jordi Goulas, Antonis Katsarou, Zoe Hardy, John Kotsis, Alexandros TI Association of the Tau haplotype with Parkinson's disease in the Greek population SO MOVEMENT DISORDERS LA English DT Article DE Tau; polymorphisms; haplotypes; Parkinson's disease ID PROGRESSIVE SUPRANUCLEAR PALSY; CORTICOBASAL DEGENERATION; GENE; H1 AB We compared the distribution of the Tau HI haplotype and related subhaplotypes in a group of clinically diagnosed Parkinson's disease patients (n = 133) and in control individuals (n = 113) from northern Greece. We were able to,detect a statistically significant overrepresentation of the H1H1 genotype in our patient group (OR for H1H1 vs. H1H2 and H2H2: 1.73; 95% Cl: 1.03-2.90; P = 0.037). The H1 subhaplotype significantly associated with the disease in our population was different from the one previously reported for a Norwegian population, suggesting that the nature of the association of Tau with Parkinson's disease is influenced by ethnic variation. (C) 2006 Movement Disorder Society. C1 Aristotle Univ Thessaloniki, Sch Med, Dept Gen Biol, GR-54124 Thessaloniki, Greece. Aristotle Univ Thessaloniki, G Papanikolau Hosp, Dept Neurol 3, GR-54006 Thessaloniki, Greece. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pharmacol, GR-54006 Thessaloniki, Greece. Reta Lila Weston Inst Neurol, London, England. RP Fidani, L (reprint author), Aristotle Univ Thessaloniki, Sch Med, Dept Gen Biol, GR-54124 Thessaloniki, Greece. EM lfidani@med.auth.gr RI Hardy, John/C-2451-2009; OI Clarimon, Jordi/0000-0002-6824-6942 FU Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 19 TC 20 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2006 VL 21 IS 7 BP 1036 EP 1039 DI 10.1002/mds.20864 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 067EW UT WOS:000239285600026 PM 16552760 ER PT J AU Schiffmann, R Hauer, P Freeman, B Ries, M Scott, LJC Polydefkis, M Brady, RO McArthur, JC Wagner, K AF Schiffmann, R Hauer, P Freeman, B Ries, M Scott, LJC Polydefkis, M Brady, RO McArthur, JC Wagner, K TI Enzyme replacement therapy and intraepidermal innervation density in Fabry disease SO MUSCLE & NERVE LA English DT Article DE epidermal innervation; Fabry disease; pain; small-fiber neuropathy ID NEUROPATHY; NERVE AB We prospectively evaluated the effect of enzyme replacement therapy (ERT) on the intraepidermal nerve fiber density (IENFD) and thermal threshold in patients with Fabry disease, an X-linked disorder associated with a painful small-fiber neuropathy and decreased linear IENFD in a length-dependent pattern. Twenty-five hemizygous male patients with Fabry disease were enrolled in a 6-month, randomized, placebo-controlled ERT trial of 0.2 mg/kg of alpha-galactosidase A (agalsidase-alfa) every 2 weeks followed by an additional 12 months of open-label ERT for both populations. IENFD and thermal threshold were measured in the distal thigh at baseline, 6 months, and 18 months from initiation of the trial. We found no significant difference in IENFD between the treatment groups at 6 months. After an additional year of ERT, there was a significant reduction in IENFD in the patient group as a whole, attributable to the declining glomerular filtration rate. Thermal thresholds remained unchanged. We conclude that epidermal nerve fiber regeneration, as measured in the distal thigh, does not occur in this patient population after 12-18 months of ERT. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM RS4e@nih.gov OI Ries, Markus/0000-0002-5054-5741 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS44807] NR 9 TC 49 Z9 49 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 2006 VL 34 IS 1 BP 53 EP 56 DI 10.1002/mus.20550 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 058TR UT WOS:000238688000005 PM 16583374 ER PT J AU Ching, YP Chan, SF Jeang, KT Jin, DY AF Ching, Yick-Pang Chan, Shing-Fai Jeang, Kuan-Teh Jin, Dong-Yan TI The retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication SO NATURE CELL BIOLOGY LA English DT Article ID CELLULAR-TRANSFORMATION; HEPATOCELLULAR-CARCINOMA; GENETIC INSTABILITY; MAMMALIAN-CELLS; CILIARY ROOTLET; TYPE-1 TAX; DUPLICATION; CENTRIOLE; CANCER; SUPPRESSOR AB Emerging evidence suggests that supernumerary centrosomes drive genome instability and oncogenesis(1-3). Human T-cell leukaemia virus type I ( HTLV-I) is etiologically associated with adult T-cell leukaemia ( ATL) 4. ATL cells are aneuploid, but the causes of aneuploidy are incompletely understood(5,6). Here, we show that centrosome amplification is frequent in HTLV-I-transformed cells and that this phenotype is caused by the viral Tax oncoprotein. We also show that the fraction of Tax protein that localizes to centrosomes interacts with TAX1BP2, a novel centrosomal protein composed almost entirely of coiled-coil domains. Overexpression of TAX1BP2 inhibited centrosome duplication, whereas depletion of TAX1BP2 by RNAi resulted in centrosome hyperamplification. Our findings suggest that the HTLV-I Tax oncoprotein targets TAX1BP2 causing genomic instability and aneuploidy. C1 Univ Hong Kong, Dept Biochem, Pokfulam, Hong Kong, Peoples R China. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Jin, DY (reprint author), Univ Hong Kong, Dept Biochem, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM dyjin@hkucc.hku.hk RI Ching, Yick Pang/C-4244-2009; Jeang, Kuan-Teh/A-2424-2008 FU FIC NIH HHS [R01 TW06186-01]; Intramural NIH HHS NR 36 TC 49 Z9 51 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUL PY 2006 VL 8 IS 7 BP 717 EP U143 DI 10.1038/ncb1432 PG 12 WC Cell Biology SC Cell Biology GA 060YJ UT WOS:000238837800014 PM 16767081 ER PT J AU Marler, JR AF Marler, JR TI Should stroke patients with mild or improving symptoms receive tissue plasminogen activator therapy? SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material DE ischemic stroke; tissue plasminogen activator ID MANAGEMENT; UPDATE C1 NINDS, Bethesda, MD 20892 USA. RP Marler, JR (reprint author), NINDS, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM marlerj@ninds.nih.gov NR 4 TC 2 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD JUL PY 2006 VL 2 IS 7 BP 354 EP 355 DI 10.1038/ncpneuro0215 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 057IN UT WOS:000238589600003 PM 16932581 ER PT J AU Chen, FH Rousche, KT Tuan, RS AF Chen, Faye H. Rousche, Kathleen T. Tuan, Rocky S. TI Technology insight: Adult stem cells in cartilage regeneration and tissue engineering SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Review DE adult stem cell; cartilage; regeneration; repair; tissue engineering ID MESENCHYMAL PROGENITOR CELLS; 3-DIMENSIONAL NANOFIBROUS SCAFFOLD; IN-VITRO CHONDROGENESIS; MARROW STROMAL CELLS; BONE-MARROW; ARTICULAR-CARTILAGE; AGAROSE CULTURE; CHONDROCYTE DIFFERENTIATION; HYDROSTATIC-PRESSURE; MICROMASS CULTURES AB Articular cartilage, the load-bearing tissue of the joint, has limited repair and regeneration potential. The scarcity of treatment modalities for large chondral defects has motivated attempts to engineer cartilage tissue constructs that can meet the functional demands of this tissue in vivo. Cartilage tissue engineering requires three components: cells, scaffold, and environment. Adult stem cells, specifically multipotent mesenchymal stem cells, are considered the cell type of choice for tissue engineering, because of the ease with which they can be isolated and expanded and their multilineage differentiation capabilities. Successful outcome of cell-based cartilage tissue engineering ultimately depends on the proper differentiation of stem cells into chondrocytes and the assembly of the appropriate cartilaginous matrix to achieve the load-bearing capabilities of the natural articular cartilage. Multiple requirements, including growth factors, signaling molecules, and physical influences, need to be met. Adult mesenchymal stem-cell-based tissue engineering is a promising technology for the development of a transplantable cartilage replacement to improve joint function. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bldg 50,Room 1523,50 South Dr,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [Z01 AR41113] NR 60 TC 163 Z9 184 U1 3 U2 53 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 JUL PY 2006 VL 2 IS 7 BP 373 EP 382 DI 10.1038/ncprheum0216 PG 10 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 061RS UT WOS:000238890700010 PM 16932723 ER PT J AU Horvath, A Boikos, S Giatzakis, C Robinson-White, A Groussin, L Griffin, KJ Stein, E Levine, E Delimpasi, G Hsiao, HP Keil, M Heyerdahl, S Matyakhina, L Libe, R Fratticci, A Kirschner, LS Cramer, K Gaillard, RC Bertagna, X Carney, JA Bertherat, J Bossis, I Stratakis, CA AF Horvath, A Boikos, S Giatzakis, C Robinson-White, A Groussin, L Griffin, KJ Stein, E Levine, E Delimpasi, G Hsiao, HP Keil, M Heyerdahl, S Matyakhina, L Libe, R Fratticci, A Kirschner, LS Cramer, K Gaillard, RC Bertagna, X Carney, JA Bertherat, J Bossis, I Stratakis, CA TI A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia SO NATURE GENETICS LA English DT Article ID ROD CGMP PHOSPHODIESTERASE; CARNEY COMPLEX; CUSHING-SYNDROME; SPLICE VARIANTS; HUMAN TISSUES; PRKAR1A GENE; DISEASE; EXPRESSION; SUBUNIT; PROTEIN AB Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome1-7. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors(8,9); its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors. C1 US Natl Inst Child Hlth & Human Dev, Sect Endocrinol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. US Natl Inst Child Hlth & Human Dev, Pediat Endocrinol Training Program, US Natl Inst Hlth, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Univ Paris 05, Hop Cochin, INSERM, U567,Inst Cochin,Dept Endocrinol Metab & Canc, F-75679 Paris, France. Univ Paris 05, Hosp Cochin, CNRS, UMR 8104,CNRS, F-75679 Paris, France. Univ Paris 05, Hosp Cochin, Ctr Reference Malad Rare Surrenale, Serv Endocrinol, F-75679 Paris, France. Ohio State Univ, Div Endocrinol, Columbus, OH 43210 USA. Ohio State Univ, Div Human Canc Genet, Columbus, OH 43210 USA. Sapio Sci LLC, York, PA 17402 USA. CHU Vaudois, Div Endocrinol Diabetol & Metab, CH-1011 Lausanne, Switzerland. RP Stratakis, CA (reprint author), US Natl Inst Child Hlth & Human Dev, Sect Endocrinol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov OI Stein, Erica/0000-0001-8778-8846 FU Intramural NIH HHS NR 30 TC 172 Z9 180 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2006 VL 38 IS 7 BP 794 EP 800 DI 10.1038/ng1809 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 058MO UT WOS:000238669300015 PM 16767104 ER PT J AU Hardy, J Cullen, K AF Hardy, John Cullen, Karen TI Amyloid at the blood vessel wall SO NATURE MEDICINE LA English DT Editorial Material ID ALZHEIMERS-DISEASE; PLAQUES; PATHOGENESIS; ANGIOPATHY; HYPOTHESIS AB An APP gene duplication found in French families with beta-amyloidopathy suggests a link between dementia and the vasculature. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Sydney, Sch Med Sci, Dept Anat & Histol, Sydney, NSW 2006, Australia. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Cullen, Karen/B-4161-2012; Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 12 TC 29 Z9 31 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2006 VL 12 IS 7 BP 756 EP 757 DI 10.1038/nm0706-756 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 061HS UT WOS:000238862800036 PM 16829930 ER PT J AU Hodes, RJ AF Hodes, Richard J. TI Public funding for Alzheimer disease research in the United States SO NATURE MEDICINE LA English DT Editorial Material C1 NIA, NIH, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NIA, NIH, Room 5C35,31 Ctr Dr, Bethesda, MD 20892 USA. EM hodesr@nia.nih.gov NR 2 TC 12 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2006 VL 12 IS 7 BP 770 EP 773 DI 10.1038/nm0706-770 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 061HS UT WOS:000238862800056 PM 16829943 ER PT J AU Thaler, C Vogel, SS Ikeda, SR Chen, HM AF Thaler, Christopher Vogel, Steven S. Ikeda, Stephen R. Chen, Huanmian TI Photobleaching of YFP does not produce a CFP-like species that affects FRET measurements SO NATURE METHODS LA English DT Letter C1 NIAAA, Lab Mol Physiol, Sect Cellular Biophoton, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Mol Physiol, Sect Transmitt Signaling, NIH, Bethesda, MD 20892 USA. RP Thaler, C (reprint author), NIAAA, Lab Mol Physiol, Sect Cellular Biophoton, NIH, Bethesda, MD 20892 USA. EM huanchen@mail.nih.gov RI Vogel, Steven/A-3585-2012 NR 2 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JUL PY 2006 VL 3 IS 7 BP 491 EP 491 DI 10.1038/nmeth0706-491a PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 058MR UT WOS:000238669600002 PM 16791204 ER PT J AU Crawford, GE Davis, S Scacheri, PC Renaud, G Halawi, MJ Erdos, MR Green, R Meltzer, PS Wolfsberg, TG Collins, FS AF Crawford, Gregory E. Davis, Sean Scacheri, Peter C. Renaud, Gabriel Halawi, Mohamad J. Erdos, Michael R. Green, Roland Meltzer, Paul S. Wolfsberg, Tyra G. Collins, Francis S. TI DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays SO NATURE METHODS LA English DT Article ID CHROMATIN-STRUCTURE; ELEMENTS; GENOME; GENES AB Mapping DNase I hypersensitive sites is an accurate method of identifying the location of gene regulatory elements, including promoters, enhancers, silencers and locus control regions. Although Southern blots are the traditional method of identifying DNase I hypersensitive sites, the conventional manual method is not readily scalable to studying large chromosomal regions, much less the entire genome. Here we describe DNase-chip, an approach that can rapidly identify DNase I hypersensitive sites for any region of interest, or potentially for the entire genome, by using tiled microarrays. We used DNase-chip to identify DNase I hypersensitive sites accurately from a representative 1% of the human genome in both primary and immortalized cell types. We found that although most DNase I hypersensitive sites were present in both cell types studied, some of them were cell-type specific. This method can be applied globally or in a targeted fashion to any tissue from any species with a sequenced genome. C1 NHGRI, NIH, Bethesda, MD 20892 USA. NimbleGen Syst Inc, Madison, WI 53711 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 31,Rooom 4B09, Bethesda, MD 20892 USA. EM francisc@exchange.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Intramural NIH HHS; NHGRI NIH HHS [K22 HG003169, K22 HG003169-01A1] NR 14 TC 132 Z9 138 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JUL PY 2006 VL 3 IS 7 BP 503 EP 509 DI 10.1038/NMETH888 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 058MR UT WOS:000238669600011 PM 16791207 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Nitro-PDI incites toxic waste accumulation SO NATURE NEUROSCIENCE LA English DT Editorial Material ID PROTEIN-DISULFIDE-ISOMERASE; PARKINSONS-DISEASE; S-NITROSYLATION; MITOCHONDRIAL DYSFUNCTION; NEURODEGENERATION; OXIDE; ALZHEIMERS; MODULATION; EXPRESSION AB In Parkinson disease and related disorders, nitric oxide may disable PDI, an enzyme critical for proper protein folding in the endoplasmic reticulum, resulting in the accumulation of damaged proteins and eventually neuronal death. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 15 TC 11 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2006 VL 9 IS 7 BP 865 EP 867 DI 10.1038/nn0706-865 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 057IZ UT WOS:000238590800006 PM 16801918 ER PT J AU Cardona, AE Pioro, EP Sasse, ME Kostenko, V Cardona, SM Dijkstra, IM Huang, DR Kidd, G Dombrowski, S Dutta, R Lee, JC Cook, DN Jung, S Lira, SA Littman, DR Ransohoff, RM AF Cardona, Astrid E. Pioro, Erik P. Sasse, Margaret E. Kostenko, Volodymyr Cardona, Sandra M. Dijkstra, Ineke M. Huang, DeRen Kidd, Grahame Dombrowski, Stephen Dutta, RanJan Lee, Jar-Chi Cook, Donald N. Jung, Steffen Lira, Sergio A. Littman, Dan R. Ransohoff, Richard M. TI Control of microglial neurotoxicity by the fractalkine receptor SO NATURE NEUROSCIENCE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE FRACTALKINE; TARGETED DELETION; IN-VIVO; BRAIN; MICE; MECHANISMS; EXPRESSION; NEURONS AB Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor ( CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1(-/-) mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1(-/-) mice showed more extensive neuronal cell loss than Cx3cr(+) littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability. C1 Cleveland Clin, Neuroinflammat Res Ctr, Cleveland, OH 44195 USA. Cleveland Clin, Dept Neurosci, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin, Dept Neurosurg, Cleveland, OH 44195 USA. Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. RP Ransohoff, RM (reprint author), Cleveland Clin, Neuroinflammat Res Ctr, Cleveland, OH 44195 USA. EM ransohr@ccf.org RI Cardona, Astrid/K-4749-2013; OI Cardona, Astrid/0000-0002-5093-8078; Jung, Steffen/0000-0003-4290-5716 FU NINDS NIH HHS [NS32151] NR 38 TC 669 Z9 679 U1 11 U2 50 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2006 VL 9 IS 7 BP 917 EP 924 DI 10.1038/nn1715 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 057IZ UT WOS:000238590800018 PM 16732273 ER PT J AU Scripture, CD Figg, WD AF Scripture, Charity D. Figg, William D. TI Drug interactions in cancer therapy SO NATURE REVIEWS CANCER LA English DT Review ID ST-JOHNS-WORT; ACUTE LYMPHOBLASTIC-LEUKEMIA; NECROSIS-FACTOR RELEASE; ACTIVATED KILLER-CELLS; PREGNANE-X-RECEPTOR; PHASE-I TRIAL; P-GLYCOPROTEIN; IMATINIB MESYLATE; GRAPEFRUIT JUICE; BREAST-CANCER AB Drug interactions in oncology are of particular importance owing to the narrow therapeutic index and the inherent toxicity of anticancer agents. Interactions with other medications can cause small changes in the pharmacokinetics or pharmacodynamics of a chemotherapy agent that could significantly alter its efficacy or toxicity. Improvements in in vitro methods and early clinical testing have made the prediction of potentially clinically significant drug interactions possible. We outline the types of drug interaction that occur in oncology, the mechanisms that underlie these interactions and describe select examples. C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 145 TC 118 Z9 126 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JUL PY 2006 VL 6 IS 7 BP 546 EP 558 DI 10.1038/nrc.1887 PG 13 WC Oncology SC Oncology GA 065ZY UT WOS:000239200200016 PM 16794637 ER PT J AU Pastan, I Hassan, R FitzGerald, DJ Kreitman, RJ AF Pastan, Ira Hassan, Raffit FitzGerald, David J. Kreitman, Robert J. TI Immunotoxin therapy of cancer SO NATURE REVIEWS CANCER LA English DT Article ID RICIN A-CHAIN; COLONY-STIMULATING FACTOR; T-CELL LYMPHOMA; PHASE-I TRIAL; ADVANCED SOLID TUMORS; PSEUDOMONAS EXOTOXIN IMMUNOCONJUGATE; REFRACTORY HODGKINS LYMPHOMA; MALIGNANT BRAIN-TUMORS; ACUTE MYELOID-LEUKEMIA; VASCULAR LEAK SYNDROME AB Rationally designed anticancer agents that target cell-surface antigens or receptors represent a promising approach for treating cancer patients. However, antibodies that bind these targets are often, by themselves, non-cytotoxic. By attaching potent toxins we can dramatically improve the clinical utility of some anti-tumour antibodies. Here we describe the construction and clinical utility of several recombinant immunotoxins; each of which is composed of antibody Fv fragments fused to powerful bacterial toxins. Results from clinical trials indicate that recombinant immunotoxins and similar agents that are designed to combine antibody selectivity with toxin cell-killing potency will be useful additions to cancer therapy. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS NR 71 TC 282 Z9 298 U1 3 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JUL PY 2006 VL 6 IS 7 BP 559 EP 565 DI 10.1038/nrc1891 PG 7 WC Oncology SC Oncology GA 065ZY UT WOS:000239200200017 PM 16794638 ER PT J AU Germain, RN Miller, MJ Dustin, ML Nussenzweig, MC AF Germain, Ronald N. Miller, Mark J. Dustin, Michael L. Nussenzweig, Michel C. TI Dynamic imaging of the immune system: progress, pitfalls and promise SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-CELL-ACTIVATION; EXCITATION FLUORESCENCE MICROSCOPY; LASER-SCANNING MICROSCOPY; IN-VIVO; DENDRITIC CELLS; LYMPH-NODES; 2-PHOTON MICROSCOPY; INTRAVITAL MICROSCOPY; BRAIN-TISSUE; 2ND-HARMONIC GENERATION AB Both innate and adaptive immunity are dependent on the migratory capacity of myeloid and lymphoid cells. Effector cells of the innate immune system rapidly enter infected tissues, whereas sentinel dendritic cells in these sites mobilize and transit to lymph nodes. In these and other secondary lymphoid tissues, interactions among various cell types promote adaptive humoral and cell-mediated immune responses. Recent advances in light microscopy have allowed direct visualization of these events in living animals and tissue explants, which allows a new appreciation of the dynamics of immune-cell behaviour. In this article, we review the basic techniques and the tools used for in situ imaging, as well as the limitations and potential artefacts of these methods. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NYU, Sch Med, Program Mol Pathogenesis, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov OI Dustin, Michael/0000-0003-4983-6389 FU Intramural NIH HHS NR 103 TC 174 Z9 183 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUL PY 2006 VL 6 IS 7 BP 497 EP 507 DI 10.1038/nri1884 PG 11 WC Immunology SC Immunology GA 056NG UT WOS:000238529900008 PM 16799470 ER PT J AU Ashwell, JD AF Ashwell, JD TI The many paths to p38 mitogen-activated protein kinase activation in the immune system SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-CELL ACTIVATION; MAP-KINASE; SIGNAL-TRANSDUCTION; IN-VIVO; INFLAMMATORY CYTOKINES; INDEPENDENT ACTIVATION; SUBSTRATE-SPECIFICITY; DUAL PHOSPHORYLATION; INDUCED APOPTOSIS; HUMAN ENDOTOXEMIA AB Signals emanating from many cell-surface receptors and environmental cues converge on mitogen-activated protein kinases (MAPKs), which in turn phosphorylate and activate various transcription factors and other molecular effectors. Members of the p38 MAPK family, which respond to pro-inflammatory cytokines and cellular stresses, are typically activated by serial phosphorylation and activation of upstream kinases (the MAPK cascade). In this Review, I highlight the recent studies that indicate that p38-subfamily members can also be activated by non-canonical mechanisms, at least one of which seems to have an important role in antigen-receptor-activated T cells. These alternative pathways might have particular relevance for cells that participate in immune and inflammatory responses. C1 NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov FU Intramural NIH HHS NR 89 TC 212 Z9 222 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUL PY 2006 VL 6 IS 7 BP 532 EP 540 DI 10.1038/nri1865 PG 9 WC Immunology SC Immunology GA 056NG UT WOS:000238529900011 PM 16799472 ER PT J AU Meshorer, E Misteli, T AF Meshorer, Eran Misteli, Tom TI Opinion - Chromatin in pluripotent embryonic stem cells and differentiation SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID H3 LYSINE-9 METHYLATION; DNA METHYLATION; GENE-EXPRESSION; NEURAL INDUCTION; SELF-RENEWAL; NUCLEAR ARCHITECTURE; SOMATIC-CELLS; MOUSE; HISTONE; GENOME AB Embryonic stem (ES) cells are unique in that they are pluripotent and have the ability to self-renew. The molecular mechanisms that underlie these two fundamental properties are largely unknown. We discuss how unique properties of chromatin in ES cells contribute to the maintenance of pluripotency and the determination of differentiation properties. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Meshorer, E (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM meshoree@mail.nih.gov; mistelit@mail.nih.gov NR 67 TC 383 Z9 394 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JUL PY 2006 VL 7 IS 7 BP 540 EP 546 DI 10.1038/nrm1938 PG 7 WC Cell Biology SC Cell Biology GA 057TQ UT WOS:000238618500019 PM 16723974 ER PT J AU Huang, Y Bayfield, MA Intine, RV Maraia, RJ AF Huang, Ying Bayfield, Mark A. Intine, Robert V. Maraia, Richard J. TI Separate RNA-binding surfaces on the multifunctional La protein mediate distinguishable activities in tRNA maturation SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID POLYMERASE-III TRANSCRIPTS; PRECURSOR TRANSFER-RNAS; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; RIBOSOMAL-RNA; NUCLEAR-RNA; NASCENT RNA; YEAST; COMPLEX; RECOGNITION AB By sequence-specific binding to 3' UUU-OH, the La protein shields precursor (pre)-RNAs from 3' end digestion and is required to protect defective pre - transfer RNAs from decay. Although La is comprised of a La motif and an RNA-recognition motif (RRM), a recent structure indicates that the RRM beta-sheet surface is not involved in UUU-OH recognition, raising questions as to its function. Progressively defective suppressor tRNAs in Schizosaccharomyces pombe reveal differential sensitivities to La and Rrp6p, a 3' exonuclease component of pre-tRNA decay. 3' end protection is compromised by mutations to the La motif but not the RRM surface. The most defective pre-tRNAs require a second activity of La, in addition to 3' protection, that requires an intact RRM surface. The two activities of La in tRNA maturation map to its two conserved RNA-binding surfaces and suggest a modular model that has implications for its other ligands. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, 31 Ctr Dr,Rm 2A25, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov FU Intramural NIH HHS NR 42 TC 46 Z9 48 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2006 VL 13 IS 7 BP 611 EP 618 DI 10.1038/nsmb1110 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 062KX UT WOS:000238944300013 PM 16799560 ER PT J AU Hama, Y Urano, Y Koyama, Y Kamiya, M Bernardo, M Paik, RS Krishna, MC Choyke, PL Kobayashi, H AF Hama, Yukihiro Urano, Yasuteru Koyama, Yoshinori Kamiya, Mako Bernardo, Marcelino Paik, Ronald S. Krishna, Murali C. Choyke, Peter L. Kobayashi, Hisataka TI In vivo spectral fluorescence imaging of submillimeter peritoneal cancer implants using a lectin-targeted optical agent SO NEOPLASIA LA English DT Article DE metastasis; optical imaging; ovarian cancer; target imaging; microfoci ID ADVANCED OVARIAN-CARCINOMA; AVIDIN; TUMOR; ACCUMULATION; SURVIVAL; LIGHT AB Intraperitoneal metastases commonly recur after surgery because small tumor foci escape detection within the complex anatomy of the peritoneal cavity and mesentery. Accurate localization of peritoneal implants during surgery could improve the resection of ovarian cancer and other malignancies, but few practical techniques to enhance detectability are currently available. Here, we describe a targeted molecular imaging method that employs fluorescently labeled avidin to detect submillimeter peritoneal implants of ovarian cancer in mice. After binding to surface lectins on the tumor, fluorescein-conjugated avidin enabled the spectral fluorescence imaging of disseminated peritoneal implants. High spatial resolution and high tumor-to-background ratio allowed the visualization of implants as small as 0.3 mm ( with 100% sensitivity and specificity; n = 150) and the identification of even smaller lesions ex vivo. These results suggest that targeted molecular imaging with a fluorescence-labeled lectin-ligand system is a promising technique for the detection of disseminated submillimeter foci of cancer. C1 NCI, NIH, Mol Imaging Program, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, NIH, Mol Imaging Program, Canc Res Ctr, Bldg 10,Room 1B40,MSC 1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS NR 20 TC 45 Z9 47 U1 0 U2 4 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL PY 2006 VL 8 IS 7 BP 607 EP U2 DI 10.1593/neo.06268 PG 8 WC Oncology SC Oncology GA 067DZ UT WOS:000239283200009 PM 16867223 ER PT J AU Panza, F D'Introno, A Colacicco, AM Capurso, C Del Parigi, A Capurso, SA Caselli, RJ Pilotto, A Scafato, E Capurso, A Solfrizzi, V AF Panza, F D'Introno, A Colacicco, AM Capurso, C Del Parigi, A Capurso, SA Caselli, RJ Pilotto, A Scafato, E Capurso, A Solfrizzi, V TI Cognitive frailty: Predementia syndrome and vascular risk factors SO NEUROBIOLOGY OF AGING LA English DT Review DE mild cognitive impairment; vascular risk factors; Alzheimer's disease; vascular dementia; APOE ID APOLIPOPROTEIN-E EPSILON-4; ALZHEIMERS-DISEASE; MEMORY IMPAIRMENT; CEREBROVASCULAR-DISEASE; E GENOTYPE; DEMENTIA; DECLINE; PREVALENCE; HEALTH; INDIVIDUALS AB With increasing emphasis on early diagnosis of Alzheimer disease (AD), clinical research has focused on the identification of risk factors that may be modified at a preclinical and early clinical stage of dementing disorders. Prevalence and incidence of different predementia syndromes vary as a result of different diagnostic criteria, as well as different sampling and assessment procedures. Particular interest in mild cognitive impairment (MCI) arises from the fact that MCI is thought to be a prodromal phase and therefore highly predictive of subsequent AD. Furthermore, many of the risk factors for cerebrovascular disease (CVD) and vascular dementia (VaD), including serum total cholesterol, hypertension, atherosclerosis, and apolipoprotein E (APOE) genotype have also been shown to increase the risk of AD. Both vascular factors and APOE epsilon 4 allele have been associated with higher risk of AD. Some recent studies suggested further that CVD or vascular factors increased the risk of conversion of MCI to dementia. This review will focus on the possible role of vascular risk factors in modulating the risk of age-related cognitive decline, and the progression of predementia syndrome such as MCI to dementia. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Bari, Dept Geriatr, Ctr Aging Brain, Mem Unit,Policlin, I-70124 Bari, Italy. Univ Foggia, Dept Geriatr, Foggia, Italy. Natl Inst Hlth, NIDDK, Phoenix, AZ USA. Mayo Clin, Dept Neurol, Scottsdale, AZ USA. IRCCS, Dept Geriatr, Casa Sollievo Sofferenza, Foggia, Italy. Ist Super Sanita, Natl Ctr Epidemiol Surveillance & Hlth Promot, I-00161 Rome, Italy. RP Panza, F (reprint author), Univ Bari, Dept Geriatr, Ctr Aging Brain, Mem Unit,Policlin, Piazza Giulio Cesare 11, I-70124 Bari, Italy. EM geriat.dot@geriatria.uniba.it; v.solfrizzi@geriatria.uniba.it OI Capurso, Cristiano/0000-0002-1152-3371; Panza, Francesco/0000-0002-7220-0656 NR 57 TC 73 Z9 75 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2006 VL 27 IS 7 BP 933 EP 940 DI 10.1016/j.neurobiolaging.2005.05.008 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 049JP UT WOS:000238012700004 PM 16023766 ER PT J AU Moffat, SD Elkins, W Resnick, SM AF Moffat, SD Elkins, W Resnick, SM TI Age differences in the neural systems supporting human allocentric spatial navigation SO NEUROBIOLOGY OF AGING LA English DT Article DE cognitive aging; navigation; spatial memory; human fMRI; Alzheimer's disease; hippocampus; parahippocampal gyrus; retro-splenial cortex ID POSITRON-EMISSION-TOMOGRAPHY; HEAD-DIRECTION CELLS; ALZHEIMERS-DISEASE; TOPOGRAPHICAL DISORIENTATION; COGNITIVE DECLINE; CINGULATE CORTEX; PLACE NAVIGATION; HIPPOCAMPUS; MEMORY; PREDICTION AB Age-related declines in spatial navigation are well-known in human and non-human species. Studies in non-human species suggest that alteration in hippocampal and other neural circuitry may underlie behavioral deficits associated with aging but little is known about the neural mechanisms of human age-related decline in spatial navigation. The purpose of the present study was to examine age differences in functional brain activation during virtual environment navigation. Voxel-based analysis of activation patterns in young subjects identified activation in the hippocampus and parahippocampal gyrus, retrosplenial cortex, right and left lateral parietal cortex, medial parietal lobe and cerebellum. In comparison to younger subjects, elderly participants showed reduced activation in the hippocampus and parahippocampal gyrus, medial parietal lobe and retrosplenial cortex. Relative to younger participants elderly subjects showed increased activation in anterior cingulate gyrus and medial frontal lobe. These results provide evidence of age specific neural networks supporting spatial navigation and identify a putative neural substrate for age-related differences in spatial memory and navigational skill. (c) 2005 Published by Elsevier Inc. C1 Gerontol Res Ctr, Lab Personal Cognit, Baltimore, MD 21224 USA. Gerontol Res Ctr, Natl Inst Aging, Baltimore, MD 21224 USA. Wayne State Univ, Dept Psychol, Inst Gerontol, Detroit, MI 48202 USA. RP Moffat, SD (reprint author), Gerontol Res Ctr, Lab Personal Cognit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moffat@wayne.edu FU Intramural NIH HHS [Z01 AG000191-11] NR 37 TC 93 Z9 98 U1 2 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2006 VL 27 IS 7 BP 965 EP 972 DI 10.1016/j.neurobiolaging.2005.05.011 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 049JP UT WOS:000238012700008 PM 15982787 ER PT J AU Turchan-Cholewo, J Liu, YL Gartner, S Reid, R Jie, CF Peng, XJ Chen, KCC Chauhan, A Haughey, N Cutler, R Mattson, MP Pardo, C Conant, K Sacktor, N McArthur, JC Hauser, KF Gairola, C Natha, A AF Turchan-Cholewo, J Liu, YL Gartner, S Reid, R Jie, CF Peng, XJ Chen, KCC Chauhan, A Haughey, N Cutler, R Mattson, MP Pardo, C Conant, K Sacktor, N McArthur, JC Hauser, KF Gairola, C Natha, A TI Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: Protection by diosgenin and L-deprenyl SO NEUROBIOLOGY OF DISEASE LA English DT Article DE drug abuse; genetics; HIV; tat; opiates; neuroprotection; ApoE4; oxidative stress ID IMMUNODEFICIENCY-VIRUS TYPE-1; DENSITY-LIPOPROTEIN RECEPTOR; APOLIPOPROTEIN-E; OXIDATIVE STRESS; TAT PROTEIN; DRUG-USERS; DEMENTIA; EXPRESSION; TOXICITY; IDENTIFICATION AB Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (ApoE) or history of intravenous drug abuse had increased oxidative stress in the CNS. In vitro studies showed that HIV proteins, gp120 and Tat, Tat + morphine but not tumor necrosis factor-alpha (TNF-alpha), caused increased neurotoxicity in human neuronal cultures with ApoE4 allele. Microarray analysis showed a differential alteration of transcripts involved in energy metabolism in cultures of ApoE3 and 4 neurons upon treatment with Tat + morphine. This was confirmed using assays of mitochondrial function and exposure of the neurons to Tat + morphine. Using this in vitro model, we screened a number of novel antioxidants and found that only L-deprenyl and diosgenin protected against the neurotoxicity of Tat + morphine. Furthermore, Tat-induced oxidative stress impaired morphine metabolism which could also be prevented by diosgenin. In conclusion, opiate abusers with HIV infection and the ApoE4 allele may be at increased risk of developing dementia. L-deprenyl and a plant estrogen, diosgenin, may have therapeutic potential in this population. (c) 2006 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Inst Med Genet, Baltimore, MD 21287 USA. Univ Kentucky, Microarray Core, Lexington, KY 40546 USA. Univ Kentucky, Dept Anat, Lexington, KY 40546 USA. Univ Kentucky, Dept Neurobiol, Lexington, KY 40546 USA. Univ Kentucky, Dept Pharm, Lexington, KY 40546 USA. NIA, Bethesda, MD 20892 USA. RP Natha, A (reprint author), Johns Hopkins Univ, Dept Neurol, 600 N Wolfe St,509 Pathol, Baltimore, MD 21287 USA. EM anath1@jhmi.edu RI Mattson, Mark/F-6038-2012 FU NCRR NIH HHS [P20RR015592]; NIMH NIH HHS [P01MH070056]; NINDS NIH HHS [R01NS039253, R01NS043990] NR 44 TC 50 Z9 54 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUL PY 2006 VL 23 IS 1 BP 109 EP 119 DI 10.1016/j.nbd.2006.02.005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 057YY UT WOS:000238632300011 PM 16697650 ER PT J AU Lerch, JP Worsley, K Shaw, WP Greenstein, DK Lenroot, RK Giedd, J Evans, AC AF Lerch, Jason P. Worsley, Keith Shaw, W. Philip Greenstein, Deanna K. Lenroot, Rhoshel K. Giedd, Jay Evans, Alan C. TI Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI SO NEUROIMAGE LA English DT Article ID ANTERIOR CINGULATE CORTEX; AUTOMATED 3-D EXTRACTION; FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; WHITE-MATTER; BROCAS AREA; GENERAL INTELLIGENCE; STATISTICAL-ANALYSIS AB We introduce MACACC-Mapping Anatomical Correlations Across Cerebral Cortex-to study correlated changes within and across different cortical networks. The principal topic of investigation is whether the thickness of one area of the cortex changes in a statistically correlated fashion with changes in thickness of other cortical regions. We further extend these methods by introducing techniques to test whether different population groupings exhibit significantly varying MACACC patterns. The methods are described in detail and applied to a normal childhood development population (n = 292), and show that association cortices have the highest correlation strengths. Taking Brodmann Area (BA) 44 as a seed region revealed MACACC patterns strikingly similar to tractography maps obtained from diffusion tensor imaging. Furthermore, the MACACC map of BA 44 changed with age, older subjects featuring tighter correlations with BA 44 in the anterior portions of the superior temporal gyri. Lastly, IQ-dependent MACACC differences were investigated, revealing steeper correlations between BA 44 and multiple frontal and parietal regions for the higher IQ group, most significantly (t = 4.0) in the anterior cingulate. (c) 2006 Published by Elsevier Inc. C1 McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Evans, AC (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. EM alan@bic.nmi.mcgill.ca RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU NIMH NIH HHS [P01MH052176-11] NR 92 TC 234 Z9 237 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2006 VL 31 IS 3 BP 993 EP 1003 DI 10.1016/j.neuroimage.2006.01.042 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 054EB UT WOS:000238358500005 PM 16624590 ER PT J AU Ozarslan, E Shepherd, TM Vemuri, BC Blackband, SJ Mareci, TH AF Ozarslan, E Shepherd, TM Vemuri, BC Blackband, SJ Mareci, TH TI Resolution of complex tissue microarchitecture using the diffusion orientation transform (DOT) SO NEUROIMAGE LA English DT Article DE MRI; tenser; anisotropy; HARDI; Fourier; spherical harmonics ID WHITE-MATTER; HUMAN BRAIN; GENERALIZED DIFFUSION; RESTRICTED DIFFUSION; WATER DIFFUSION; FIELD GRADIENT; WEIGHTED MRI; SPIN ECHOES; TENSOR; ANISOTROPY AB This article describes an accurate and fast method for fiber orientation mapping using multidirectional diffusion-weighted magnetic resonance (MR) data. This novel approach utilizes the Fourier transform relationship between the water displacement probabilities and diffusion-attenuated MR signal expressed in spherical coordinates. The radial part of the Fourier integral is evaluated analytically under the assumption that MR signal attenuates exponentially. The values of the resulting functions are evaluated at a fixed distance away from the origin. The spherical harmonic transform of these functions yields the Laplace series coefficients of the probabilities on a sphere of fixed radius. Alternatively, probability values can be computed nonparametrically using Legendre polynomials. Orientation maps calculated from excised rat nervous tissue data demonstrate this technique's ability to accurately resolve crossing fibers in anatomical regions such as the optic chiasm. This proposed methodology has a trivial extension to multiexponential diffusion-weighted signal decay. The developed methods will improve the reliability of tractography schemes and may make it possible to correctly identify the neural connections between functionally connected regions of the nervous system. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Florida, Dept Comp & Informat Sci & Engn, Gainesville, FL 32611 USA. Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. RP Ozarslan, E (reprint author), NIH, 13 S Dr,Rm 3W16, Bethesda, MD 20892 USA. EM evren@helix.nih.gov RI Ozarslan, Evren/B-4858-2013 OI Ozarslan, Evren/0000-0003-0859-1311 FU NCRR NIH HHS [P41-RR16105]; NINDS NIH HHS [R01-NS36992, R01-NS42075] NR 42 TC 210 Z9 210 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2006 VL 31 IS 3 BP 1086 EP 1103 DI 10.1016/j.neuroimage.2006.01.024 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 054EB UT WOS:000238358500013 PM 16546404 ER PT J AU Balsamo, LM Xu, B Gaillard, WD AF Balsamo, LM Xu, B Gaillard, WD TI Language lateralization and the role of the fusiform gyrus in semantic processing in young children SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; NEURAL-NETWORKS; SENTENCE COMPREHENSION; AUDITORY COMPREHENSION; COGNITIVE-DEVELOPMENT; BRAIN ACTIVATION; CORTICAL ANATOMY; MENTAL-IMAGERY; FMRI AB We used blood oxygen-dependent (BOLD) fMRI technique at 1.5 T to examine brain regions associated with language comprehension in normally developing children, age 5 to 10 years. Twenty-three children participated in the study using an auditory semantic decision task which varied in task difficulty. Analysis of individual participants' data showed patterns of activation largely consistent with previous neuro-imaging findings in adult language processing. Group data analysis also showed a strong left-lateralized pattern of activation that closely resembles those typically observed in adults. In addition, significant activation in the left fusiform gyrus was observed and was associated with task accuracy. This finding suggests that auditory semantic processing in young children may recruit cortical regions associated with word reading in adults prior to the initiation of a semantic category decision, a process which is consistent with patterns of early word recognition process and language development. (c) 2006 Elsevier Inc. All rights reserved. C1 George Washington Univ, Dept Neurol, Sch Med, Childrens Natl Med Ctr, Washington, DC 20010 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Gaillard, WD (reprint author), George Washington Univ, Dept Neurol, Sch Med, Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM gaillardw@ninds.nih.gov NR 74 TC 43 Z9 45 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2006 VL 31 IS 3 BP 1306 EP 1314 DI 10.1016/j.neuroimage.2006.01.027 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 054EB UT WOS:000238358500033 PM 16545581 ER PT J AU Kernich, CA AF Kernich, Catherine A. TI Diplopia SO NEUROLOGIST LA English DT Editorial Material C1 Univ Hosp Hlth Sys, Univ Hosp Fac Serv, Dept Med, Cleveland, OH USA. RP Kernich, CA (reprint author), NEI, NIH, 2020 Vis Pl, 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 1074-7931 J9 NEUROLOGIST JI Neurologist PD JUL PY 2006 VL 12 IS 4 BP 229 EP 230 DI 10.1097/01.nrl.0000231927.93645.34 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 062ZX UT WOS:000238986700007 PM 16832242 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. TI Inflammatory myopathies SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S143 EP S143 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400355 ER PT J AU Fischbeck, KH AF Fischbeck, Kenneth H. TI Polyglutamine repeat disorders SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S103 EP S103 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400206 ER PT J AU Fischbeck, KH AF Fischbeck, Kenneth H. TI From genes to proteins SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S48 EP S48 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400002 ER PT J AU Fischer, D Clemen, CC Olive, M Ferrer, I Vicart, P Goldfarb, LG Moza, M Carpen, O Schroder, R AF Fischer, Dirk Clemen, Christoph C. Olive, Montse Ferrer, Isidro Vicart, Patrick Goldfarb, Lev G. Moza, Monica Carpen, Olli Schroeder, Rolf TI The early pathogenesis of myotilinopathy is different to primary desminopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Univ Bonn, Dept Neurol, Muskellab, D-5300 Bonn, Germany. Univ Cologne, Fac Med, Ctr Biochem, Cologne, Germany. Bellvitge Hosp, IDIBELL, Inst Neuropatol, Barcelona, Spain. Univ Paris 07, UFR Biochem, Paris, France. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Univ Turku, Dept Pathol, SF-20500 Turku, Finland. Univ Turku, Cent Hosp, SF-20500 Turku, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S61 EP S62 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400049 ER PT J AU Goebel, HH Schroeder, R Schulz-Schaeffer, W Goldfarb, L AF Goebel, Hans H. Schroeder, Rolf Schulz-Schaeffer, Walter Goldfarb, Lev TI A comparative morphological study of heart and skeletal muscle in mutation-proven desminopathie SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Univ Mainz, Med Ctr, Dept Neuropathol, D-6500 Mainz, Germany. Univ Cologne, Ctr Biochem, D-5000 Cologne 41, Germany. Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S87 EP S87 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400145 ER PT J AU Kostera-Pruszczyk, A Pruszczyk, P Shatunov, A Goudeau, B Draminska, A Takeda, K Sambuughin, N Vicart, P Strelkov, SV Goldfarb, LG Kaminska, A AF Kostera-Pruszczyk, Anna Pruszczyk, Piotr Shatunov, Alexey Goudeau, Bertrand Draminska, Agnieszka Takeda, Kazuyo Sambuughin, Nyamkhishig Vicart, Patrick Strelkov, Sergei V. Goldfarb, Lev G. Kaminska, Anna TI Skeletal myopathy and restrictive cardiomyopathy with atrioventricular conduction block resulting from desmin mutation SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Med Univ Warsaw, Dept Neurol, Warsaw, Poland. Med Univ Warsaw, Dept Internal Med Hypertens & Angiol, Warsaw, Poland. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. Univ Paris 06, CNRS, UMR 7000, F-75013 Paris, France. Univ Paris 07, UFR Biochim, F-75005 Paris, France. Univ Basel, Bioctr, ME Muller Inst Struct Biol, CH-4056 Basel, Switzerland. Polish Acad Sci, Med Res Ctr, Neuromuscular Unit, Warsaw, Poland. RI Shatunov, Aleksey/E-6946-2011; Strelkov, Sergei/G-7425-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S61 EP S61 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400048 ER PT J AU Olive, M Shatunov, A Goldfarb, L Pou, A Armstrong, J Moreno, D Pradas, J Huerta, M Fischer, D Povedano, M Jauma, S Ferrer, I AF Olive, Montse Shatunov, Alexey Goldfarb, Lev Pou, Adolf Armstrong, Judith Moreno, Dolores Pradas, Jesus Huerta, Mariano Fischer, Dirk Povedano, Monica Jauma, Serge Ferrer, Isidro TI Clinical, morphological and genetic characterization of a series of 27 Spanish patients with myofibrillar myopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Bellvitge Hosp, IDIBELL, Barcelona, Spain. NIH, Bethesda, MD 20892 USA. Hosp Mar, Barcelona, Spain. Hosp Sant Pau, Barcelona, Spain. Hosp Viladecans, Barcelona, Spain. Univ Bonn, Neurol Klin, D-5300 Bonn, Germany. RI Shatunov, Aleksey/E-6946-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S108 EP S108 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400226 ER PT J AU Raben, N Fukuda, T Plotz, P AF Raben, Nina Fukuda, Tokiko Plotz, Paul TI Pompe disease and therapeutic options SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S192 EP S192 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400540 ER PT J AU Zhu, YX Jiang, JH Li, XM McVie-Wylie, A Jiang, C Raben, BTN Mattaliano, R Cheng, S AF Zhu, Yunxiang Jiang, Jinhua Li, Xuemei McVie-Wylie, Alison Jiang, Canwen Raben, Beth Thurberg Nina Mattaliano, Robert Cheng, Seng TI Carbohydrate-remodeled acid alpha-glucosidase with higher affinity for the cation-independent mannose 6-phosphate receptor demonstrates improved delivery to muscles of Pompe mice SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress on Neuromuscular Diseases CY JUL 02-07, 2006 CL Istanbul, TURKEY C1 Genzyme Corp, Framingham, MA 01701 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUL PY 2006 VL 16 SU 1 BP S182 EP S182 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 066KX UT WOS:000239229400502 ER PT J AU Xi, ZX Newman, AH Gilbert, JG Pak, AC Peng, XQ Ashby, CR Gitajn, L Gardner, EL AF Xi, ZX Newman, AH Gilbert, JG Pak, AC Peng, XQ Ashby, CR Gitajn, L Gardner, EL TI The novel dopamine D-3 receptor antagonist NGB 2904 inhibits cocaine's rewarding effects and cocaine-induced reinstatement of drug-seeking behavior in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14, 2004 CL San Juan, PR SP Coll Problems Drug Dependence DE cocaine; D-3 receptor; NGB 2904; self-administration; brain reward; relapse ID BRAIN-STIMULATION REWARD; NUCLEUS-ACCUMBENS DOPAMINE; PROGRESSIVE-RATIO; D3 RECEPTOR; SELF-STIMULATION; REINFORCING EFFICACY; LOCOMOTOR-ACTIVITY; PARTIAL AGONIST; HIGH-AFFINITY; SCHEDULES AB Accumulating evidence indicates that dopamine (DA) D-3 receptor antagonists appear highly promising in attenuating cocaine reward and relapse in preclinical models of addiction. In the present study, we investigated the effects of the novel D-3-selective antagonist NGB 2904 (N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-3-fluorenylcarboxamide) on cocaine self-administration, cocaine-enhanced brain stimulation reward (BSR), and cocaine-triggered reinstatement of drug-seeking behavior in male Long-Evans rats. We found that: (1) acute intraperitoneal (i.p.) administration of NGB 2904 (0.1-10 mg/kg) failed to alter cocaine self-administration (0.5 mg/kg/ infusion) under fixed-ratio 2 (FR2) reinforcement, but 1 or 5 mg/kg NGB 2904 significantly lowered the break-point for cocaine self-administration under progressive-ratio (PR) reinforcement; (2) cocaine (1, 2, and 10 mg/kg) significantly enhanced electrical BSR (decreased brain reward thresholds), while NGB 2904 significantly inhibited the enhancement of BSR elicited by 2 mg/kg, but not 10 mg/kg of cocaine; (3) NGB 2904 alone neither maintained self-administration behavior nor altered brain reward thresholds; and ( 4) NGB 2904 significantly inhibited cocaine-triggered reinstatement of extinguished drug-seeking behavior, but not sucrose-plus-sucrose-cue-triggered reinstatement of sucrose-seeking behavior. Overall, these data show that the novel D-3-selective antagonist NGB 2904 attenuates cocaine's rewarding effects as assessed by PR self-administration, BSR, and cocaine-triggered reinstatement of cocaine-seeking behavior. Owing to these properties and to its lack of rewarding effects ( as assessed by BSR and by substitution during drug self-administration), NGB 2904 merits further investigation as a potential agent for treatment of cocaine addiction. C1 NIDA, Neuropsychopharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. St Johns Univ, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. RP Xi, ZX (reprint author), NIDA, Neuropsychopharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Bldg C,Room 394,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov OI PENG, XIAOQING/0000-0002-7272-5428 FU Intramural NIH HHS NR 98 TC 97 Z9 97 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2006 VL 31 IS 7 BP 1393 EP 1405 DI 10.1038/sj.npp.1300912 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 054ZR UT WOS:000238418700006 PM 16205781 ER PT J AU Newton, TF Roache, JD De La Garza, R Fong, T Wallace, CL Li, SH Elkashef, A Chiang, N Kahn, R AF Newton, TF Roache, JD De La Garza, R Fong, T Wallace, CL Li, SH Elkashef, A Chiang, N Kahn, R TI Bupropion reduces methamphetamine-induced subjective effects and cue-induced craving SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE human; dopamine; norepinepherine; addiction; dependence ID POSITRON-EMISSION-TOMOGRAPHY; CENTER INVENTORY ARCI; DOPAMINE TRANSPORTER; PHARMACOLOGICAL-TREATMENT; COCAINE DEPENDENCE; ABUSE; IMIPRAMINE; ADDICTION; NOREPINEPHRINE; QUESTIONNAIRE AB Bupropion is an antidepressant with stimulant properties, which inhibits the reuptake of dopamine (DA) and norepinepherine, and is purported to enhance DA neurotransmission. Bupropion is considered an appealing candidate medication for the treatment of methamphetamine dependence. The current laboratory study was set forth to assess the impact of bupropion treatment on the subjective effects produced by methamphetamine in the laboratory. We also assessed the effects of bupropion treatment on craving elicited by exposure to videotaped methamphetamine cues. A total of 26 participants were enrolled and 20 completed the entire study (n = 10 placebo and n = 10 bupropion, parallel groups design). Bupropion treatment was associated with reduced ratings of 'any drug effect' (p < 0.02), and 'high' (p < 0.02) following methamphetamine administration. There was also a significant bupropion-by-cue exposure interaction on General Craving Scale total score (p < 0.002), and on the Behavioral Intention subscale (p < 0.001). Overall, the data reveal that bupropion reduced acute methamphetamine-induced subjective effects and reduced cue-induced craving. Importantly, these data provide a rationale for the evaluation of bupropion in the treatment of methamphetamine dependence. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Psychiat, Univ Clin Psychopharmacol Lab, San Antonio, TX 78285 USA. NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. RP Newton, TF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 740 Westwood Blvd,Suite A7-372, Los Angeles, CA 90024 USA. EM tnewton@mednet.ucla.edu RI De La Garza, Richard/B-2489-2014; OI De La Garza, Richard/0000-0003-1943-4469; newton, thomas/0000-0002-3198-5901 FU NCRR NIH HHS [RR-00865]; NIDA NIH HHS [DA-08804, DA 014593] NR 48 TC 93 Z9 97 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2006 VL 31 IS 7 BP 1537 EP 1544 DI 10.1038/sj.npp.1300979 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 054ZR UT WOS:000238418700019 PM 16319910 ER PT J AU Bindewald, E Schneider, TD Shapiro, BA AF Bindewald, Eckart Schneider, Thomas D. Shapiro, Bruce A. TI CorreLogo: an online server for 3D sequence logos of RNA and DNA alignments SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CRYSTAL-STRUCTURE; MATHEMATICAL-THEORY; BINDING-SITES; ACCEPTOR-STEM; INFORMATION; COMMUNICATION; RECOGNITION; CONSTRAINTS; ANTICODON; DATABASE AB We present an online server that generates a 3D representation of properties of user- submitted RNA or DNA alignments. The visualized properties are information of single alignment columns, mutual information of two alignment positions as well as the position- specific fraction of gaps. The nucleotide composition of both single columns and column pairs is visualized with the help of color- coded 3D bars labeled with letters. The server generates both VRML and JVX output that can be viewed with a VRML viewer or the JavaView applet, respectively. We show that combining these different features of an alignment into one 3D representation is helpful in identifying correlations between bases and potential RNA and DNA base pairs. Significant known correlations between the tRNA 30 anticodon cardinal nucleotide and the extended anticodon were observed, as were correlations within the amino acid acceptor stem and between the cardinal nucleotide and the acceptor stem. The online server can be accessed using the URL http://correlogo.abcc.ncifcrf.gov. C1 NCI Frederick, SAIC Frederick, Bas Res Program, Ft Detrick, MD 21702 USA. NCI Frederick, Canc Res Ctr, Nanobiol Program, Ft Detrick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI Frederick, SAIC Frederick, Bas Res Program, Ft Detrick, MD 21702 USA. EM bshapiro@ncifcrf.gov OI Schneider, Thomas/0000-0002-9841-1531 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 37 TC 17 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2006 VL 34 SI SI BP W405 EP W411 DI 10.1093/nar/gkl269 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156LR UT WOS:000245650200082 PM 16845037 ER PT J AU Dror, O Nussinov, R Wolfson, HJ AF Dror, Oranit Nussinov, Ruth Wolfson, Haim J. TI The ARTS web server for aligning RNA tertiary structures SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CRYSTAL-STRUCTURE; IDENTIFICATION; DISCOVERY; MOTIFS; REPRESENTATION; REPERTOIRE; COMPLEX AB RNA molecules with common structural features may share similar functional properties. Structural comparison of RNAs and detection of common substructures is, thus, a highly important task. Nevertheless, the current available tools in the RNA community provide only a partial solution, since they either work at the 2D level or are suitable for detecting predefined or local contiguous tertiary motifs only. Here, we describe a web server built around ARTS, a method for aligning tertiary structures of nucleic acids ( both RNAandDNA). ARTS receives a pair of 3D nucleic acid structures and searches for a priori unknown common substructures. The search is truly 3D and irrespective of the order of the nucleotides on the chain. The identified common substructures can be large global folds with hundreds and even thousands of nucleotides as well as small local motifs with at least two successive base pairs. The method is highly efficient and has been used to conduct an all-against-all comparison of all the RNA structures in the Protein Data Bank. The web server together with a software package for downloadare freely accessible at http://bioinfo3d.cs.tau.ac.il/ARTS. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. NCI Frederick, Basic Res Program, SAIC Frederick, Ctr Canc Res,Neurobiol Program, Ft Detrick, MD 21702 USA. RP Dror, O (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM oranit@post.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 27 TC 32 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2006 VL 34 SI SI BP W412 EP W415 DI 10.1093/nar/gkl312 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156LR UT WOS:000245650200083 PM 16845038 ER PT J AU Khatri, P Desai, V Tarca, AL Sellamuthu, S Wildman, DE Romero, R Draghici, S AF Khatri, Purvesh Desai, Valmik Tarca, Adi L. Sellamuthu, Sivakumar Wildman, Derek E. Romero, Roberto Draghici, Sorin TI New Onto-Tools: Promoter-Express, nsSNPCounter and Onto-Translate SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; SEQUENCE TAGS; CELL-CYCLE; RESOURCE; DATABASE; GENOME; IDENTIFICATION; KNOWLEDGEBASE; SELECTION; COMPARE AB The Onto- Tools suite is composed of an annotation database and eight complementary, web- accessible data mining tools: Onto- Express, Onto- Compare, Onto- Design, Onto- Translate, Onto- Miner, PathwayExpress, Promoter- Express and nsSNPCounter. Promoter- Express is a new tool added to the Onto- Toolsensemble that facilitates the identification of transcription factor binding sites active in specific conditions. nsSNPCounter is another new tool that allows computation and analysis of synonymous and non- synonymous codon substitutions for studying evolutionary rates of protein coding genes. Onto- Translate has also been enhanced to expand its scope and accuracy by fully utilizing the capabilities of the Onto- Tools database. Currently, Onto- Translate allows arbitrary mappings between 28 types of IDs for 53 organisms. Onto- Tools are freely available at http://vortex.cs.wayne.edu/Projects.html. C1 Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. NICHD, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. RP Draghici, S (reprint author), Wayne State Univ, Dept Comp Sci, 431 State Hall, Detroit, MI 48202 USA. EM sorin@wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Intramural NIH HHS; NCI NIH HHS [1R21 CA10074001]; NCRR NIH HHS [1S10 RR017857-01, S10 RR017857]; NHGRI NIH HHS [1R01HG003491-01A1, R01 HG003491]; NIBIB NIH HHS [1R21 EB00990-01, R21 EB000990]; NINDS NIH HHS [1R01 NS045207-01, R01 NS045207] NR 35 TC 16 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2006 VL 34 SI SI BP W626 EP W631 DI 10.1093/nar/gkl213 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156LR UT WOS:000245650200126 PM 16845086 ER PT J AU Mudunuri, U Stephens, R Bruining, D Liu, D Lebeda, FJ AF Mudunuri, Uma Stephens, Robert Bruining, David Liu, David Lebeda, Frank J. TI botXminer: mining biomedical literature with a new web-based application SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PUBMED ABSTRACTS; GENE-EXPRESSION; NETWORK; TOOL AB This paper outlines botXminer, a publicly available application to search XML-formatted MEDLINE (R) data in a complete, object-relational schema implemented in Oracle (R) XML DB. An advantage offered by botXminer is that it can generate quantitative results with certain queries that are not feasible through the Entrez-PubMed (R) interface. After retrieving citations associated with user-supplied search terms, MEDLINE fields (title, abstract, journal, MeSH (R) and chemical) and terms ( MeSH qualifiers and descriptors, keywords, author, gene symbol and chemical), these citations are grouped and displayed as tabulated or graphic results. This work represents an extension of previous research for integrating these citations with relational systems. botXminer has a user-friendly, intuitive interface that can be freely accessed at http://botdb.abcc.ncifcrf.gov. C1 NCI, Sci Applicat Int Corp, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD 21702 USA. RP Lebeda, FJ (reprint author), NCI, Sci Applicat Int Corp, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. EM frank.lebeda@amedd.army.mil FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 10 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2006 VL 34 SI SI BP W748 EP W752 DI 10.1093/nar/gkl194 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156LR UT WOS:000245650200151 PM 16845112 ER PT J AU Ye, J McGinnis, S Madden, TL AF Ye, Jian McGinnis, Scott Madden, Thomas L. TI BLAST: improvements for better sequence analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article AB Basic local alignment search tool (BLAST) is a sequence similarity search program. The National Center for Biotechnology Information (NCBI) maintains a BLAST server with a home page at http:// www.ncbi.nlm.nih.gov/BLAST/. We report here on recent enhancements to the results produced by the BLAST server at the NCBI. These include features to highlight mismatches between similar sequences, show where the query was masked for low-complexity sequence, and integrate information about the database sequences from the NCBI Entrez system into the BLAST display. Changes to how the database sequences are fetched have also improved the speed of the report generator. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Madden, TL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM madden@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 6 TC 132 Z9 135 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2006 VL 34 SI SI BP W6 EP W9 DI 10.1093/nar/gkl164 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156LR UT WOS:000245650200002 PM 16845079 ER PT J AU Bloom, SL Leveno, KJ Spong, CY Gilbert, S Hauth, JC Landon, MB Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M O'Sullivan, MJ Sibai, BM Langer, O Gabbe, SG AF Bloom, Steven L. Leveno, Kenneth J. Spong, Catherine Y. Gilbert, Sharon Hauth, John C. Landon, Mark B. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Gabbe, Steven G. CA Natl Inst Child Hlth Human Dev TI Decision-to-incision times and maternal and infant outcomes SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID EMERGENCY CESAREAN DELIVERY; SECTION AB OBJECTIVE: To measure decision-to-incision intervals and related maternal and neonatal outcomes in a cohort of women undergoing emergency cesarean deliveries at multiple university-based hospitals comprising the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. METHODS: All women undergoing a primary cesarean delivery at a Network center during a 2-year time span were prospectively ascertained. Emergency procedures were defined as these performed for umbilical cord prolapse, placental abruption, placenta previa with hemorrhage, nonreassuring fetal heart rate pattern, or uterine rupture. Detailed information regarding maternal and neonatal outcomes, including the interval from the decision time to perform cesarean delivery to the actual skin incision, was collected. RESULTS: Of the 11,481 primary cesarean deliveries, 2,808 were performed for an emergency indication. Of these, 1,814 (65%) began within 30 minutes of the decision to operate. Maternal complication rates, including endometritis, wound infection, and operative injury, were not related to the decision-to-incision interval. Measures of newborn compromise including umbilical artery pH less than 7 and intubation in the delivery room were significantly greater when the cesarean delivery was commenced within 30 minutes, likely attesting to the need for expedited delivery. Of the infants with indications for an emergency cesarean delivery who were delivered more than 30 minutes after the decision to operate, 95% did not experience a measure of newborn compromise. CONCLUSION: Approximately one third of primary cesarean deliveries performed for emergency indications are commenced more than 30 minutes after the decision to operate, and the majority were for nonreassuring heart rate tracings. In these cases, adverse neonatal outcomes were not increased. C1 Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75230 USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Miami Univ, Dept Obstet & Gynecol, Miami, FL USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN USA. Univ Texas, Ctr Hlth Sci, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. Vanderbilt Univ, Ctr Med, Dept Obstet & Gynecol, Nashville, TN USA. RP Bloom, SL (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75230 USA. EM steven.bloom@utsouthwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD27915, HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801] NR 8 TC 69 Z9 72 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2006 VL 108 IS 1 BP 6 EP 11 DI 10.1097/01.AOG.0000224693.07785.14 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XF UT WOS:000246768000003 PM 16816049 ER PT J AU Landon, MB Spong, CY Thom, E Hauth, JC Bloom, SL Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG AF Landon, Mark B. Spong, Catherine Y. Thom, Elizabeth Hauth, John C. Bloom, Steven L. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan M. O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. Gabbe, Steven G. TI Risk of uterine rupture with a trial of labor in women with multiple and single prior cesarean delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID VAGINAL BIRTH; OUTCOMES AB OBJECTIVE: To determine whether the risk for uterine rupture is increased in women attempting vaginal birth after multiple cesarean deliveries. METHODS: We conducted a prospective multicenter observational study of women with prior cesarean delivery undergoing trial of labor and elective repeat operation. Maternal and perinatal outcomes were compared among women attempting vaginal birth after multiple cesarean deliveries and those with a single prior cesarean delivery. We also compared outcomes for women with multiple prior cesarean deliveries undergoing trial of labor with those electing repeat cesarean delivery. RESULTS: Uterine rupture occurred in 9 of 975 (0.9%) women with multiple prior cesarean compared with 115 of 16,915 (0.7%) women with a single prior operation (P = .37). Multivariable analysis confirmed that multiple prior cesarean delivery was not associated with an increased risk for uterine rupture. The rates of hysterectomy (0.6%,) versus 0.2%, P =.023) and transfusion (3.2% versus 1.6%, P <.001) were increased in women with multiple prior cesarean deliveries compared with women with a single prior cesarean delivery attempting trial of labor. Similarly, a composite of maternal morbidity was increased in women with multiple prior cesarean deliveries undergoing trial of labor compared with those having elective repeat cesarean delivery (odds ratio 1.41, 95% confidence interval 1.02-1.93). CONCLUSION: A history of multiple cesarean deliveries is not associated with an increased rate of uterine rupture in women attempting vaginal birth compared with those with a single prior operation. Maternal morbidity is increased with trial of labor after multiple cesarean deliveries, compared with elective repeat cesarean delivery, but the absolute risk for complications is small. Vaginal birth after multiple cesarean deliveries should remain an option for eligible women. C1 Ohio State Univ, Coll Med & Publ Hlth, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Alabama, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH 45221 USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Miami Univ, Dept Obstet & Gynecol, Miami, FL USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN USA. Univ Texas, Ctr Hlth Sci, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, Houston, TX USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC USA. RP Landon, MB (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Dept Obstet & Gynecol, 1654 Upham Dr,Means Hall 5th Floor, Columbus, OH 43210 USA. EM landon.1@osu.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD34136, HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 11 TC 87 Z9 92 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2006 VL 108 IS 1 BP 12 EP 20 DI 10.1097/01.AOG.0000224694.32531.f3 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XF UT WOS:000246768000004 PM 16816050 ER PT J AU Hendler, I Schat, M Momirova, V Wise, R Landon, M Mabie, W Newman, RB Newman, JB Kiley, J Hauth, JC Moawad, A Caritis, SN Spong, CY Leveno, KJ Miodovnik, M Meis, P Wapner, RJ Paul, RH Varner, MW O'Sullivan, MJ Thurnau, GR Conway, DL AF Hendler, Israel Schat, Michael Momirova, Valerija Wise, Robert Landon, Mark Mabie, William Newman, Roger B. Newman, James B. Kiley, James Hauth, John C. Moawad, Atef Caritis, Steve N. Spong, Catherine Y. Leveno, Kenneth J. Miodovnik, Menachem Meis, Paul Wapner, Ronald J. Paul, Richard H. Varner, Michael W. O'Sullivan, Mary Jo Thurnau, Gary R. Conway, Deborah L. TI Association of obesity with pulmonary and nonpulmonary complications of pregnancy in asthmatic women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BODY-MASS INDEX; WEIGHT-REDUCTION; HEALTH SURVEYS; RISK; POPULATION; OUTCOMES; PREVALENCE; SYMPTOMS; INCREASE; MEN AB OBJECTIVE: To evaluate whether maternal obesity is associated with pulmonary and nonpulmonary pregnancy complications in asthmatic women. METHODS: This is a secondary analysis of the prospective cohort Asthma During Pregnancy Study. Asthma patients were classified as having either mild or moderate to severe disease at the beginning of the study. Rates of pulmonary complications of asthma in asthmatic women and rates of nonpulmonary complications of pregnancy among asthma patients and controls, were compared between obese (body mass index >= 30 kg/m(2)) and nonobese women. RESULTS: Maternal body mass index and pregnancy outcome data were available for 1,699 of 1,812 asthmatic women and for 867 of 881 controls. Of the asthma subjects, 30.7% (521) were obese compared with 25.5% of the controls, P =.006. Obese women, regardless of whether they had asthma, were more likely to undergo cesarean delivery (OR 1.6, 95% confidence interval [CI]1.3-2.0) to develop preeclampsia or gestational hypertension (OR 1.7 95% CI 1.3-2.3) and gestational diabetes (OR 4.2, 95% CI 2.8-6.3). There were no differences in the rates of overall asthma improvement (20.6% compared with 23.6%, P =.36) or deterioration (33.3% compared with 28.8%, P =.20) between obese and nonobese asthma patients. After adjustment for confounding variables, obesity, not asthma, was associated with nonpulmonary complications of pregnancy, and obesity was associated with an increase in asthma exacerbations as well (OR 1.3, 95% CI 1.1-1.7). CONCLUSION: Obesity is associated with an increased risk of asthma exacerbations during pregnancy. The increased rate of nonpulmonary complications of pregnancy in asthma patients is associated with obesity in this population and not with asthma status. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Kaiser Permanente, Dept Allergy, San Diego, CA USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Johns Hopkins Univ, Dept Pulm Med, Baltimore, MD USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. NHLBI, Bethesda, MD 20892 USA. Dept Obstet & Gynecol, Birmingham, AL USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. NICHHD, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Oklahoma, Dept Obstet & Gynecol, Norman, OK 73019 USA. Univ Texas, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. RP Hendler, I (reprint author), Wayne State Univ, Hutzel Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, 3990 John R St, Detroit, MI 48201 USA. EM ihendler@med.wayne.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Wise, Robert/0000-0002-8353-2349; Varner, Michael/0000-0001-9455-3973 NR 27 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2006 VL 108 IS 1 BP 77 EP 82 DI 10.1097/01.AOG.0000223180.53113.0f PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XF UT WOS:000246768000013 PM 16816059 ER PT J AU Hibbard, JU Gilbert, S Landon, MB Hauth, JC Leveno, KJ Spong, CY Varner, MW Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG AF Hibbard, Judith U. Gilbert, Sharon Landon, Mark B. Hauth, John C. Leveno, Kenneth J. Spong, Catherine Y. Varner, Michael W. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan M. O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. Gabbe, Steven G. TI Trial of labor or repeat cesarean delivery in women with morbid obesity and previous cesarean delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med ID VAGINAL BIRTH; MATERNAL OBESITY; UTERINE RUPTURE; SECTION; OUTCOMES; RISK; SUCCESS AB OBJECTIVE: Assess effects of body mass index (BMI) on trial of labor after previous cesarean delivery and determine whether morbidly obese women have greater maternal and perinatal morbidity with trial of labor compared with elective repeat cesarean delivery. METHODS: Secondary analysis from a prospective observational study included all term singletons undergoing trial of labor after previous cesarean delivery. Body mass index groups were as follows: normal 18.5-24.9, overweight 25.0-29.9, obese 30.0-39.9, morbidly obese 40.0 kg/m(2) or greater, and were compared for failure and maternal and neonatal morbidities. The morbidly obese trial of labor and elective repeat cesarean delivery were compared for maternal and neonatal morbidities. Multivariable logistic regression analysis controlled for confounding variables. RESULTS: There were 14,142 trial of labor participants and 14,304 elective repeat cesarean delivery participants. Increasing BMI was directly associated with failed trial of labor after previous cesarean delivery: from 15.2% in normal weight (1,344) to 39.3% in morbidly obese (1,638), with combined risk of rupture/dehiscence increasing from 0.9% to 2.1% in morbidly obese women. Among morbidly obese women, trial of labor carried greater than five-fold risk of uterine rupture/dehiscence (2.1% versus 0.4%), almost a two-fold increase in composite maternal morbidity (7.2% versus 3.8%) and five-fold risk of neonatal injury (1.1% versus 0.2%) (fractures, brachial plexus injuries, and lacerations), but no neonatal encephalopathy. Morbidly obese women failing a trial of labor had six-fold greater composite maternal morbidity than those undergoing a successful trial of labor (14.2% versus 2.6%). CONCLUSION: Body mass index correlates with outcomes in trial of labor after previous cesarean delivery. Morbidly obese women undergoing a trial of labor were at increased risk for failure. Increased BMI was associated with greater composite morbidity and neonatal injury compared C1 Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Alabama, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NICHHD, Bethesda, MD 20892 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vanderbilt Univ, Nashville, TN USA. RP Hibbard, JU (reprint author), Univ Illinois, Dept Obstet & Gynecol, 820 S Wood St,MC 808, Chicago, IL 60612 USA. EM jhibbar@uic.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 NR 18 TC 84 Z9 85 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2006 VL 108 IS 1 BP 125 EP 133 DI 10.1097/01.AOG.0000223871.69852.31 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XF UT WOS:000246768000020 PM 16816066 ER PT J AU Sallmen, M Baird, DD Hoppin, JA Blair, A Sandler, DP AF Sallmen, M Baird, DD Hoppin, JA Blair, A Sandler, DP TI Fertility and exposure to solvents among families in the Agricultural Health Study SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ETHYLENE-GLYCOL ETHERS; ORGANIC-SOLVENTS; OCCUPATIONAL EXPOSURES; SEMICONDUCTOR WORKERS; REDUCED FERTILITY; PREGNANCY; TIME; INFERTILITY; TOLUENE; WIVES AB Background: Several studies have reported associations between solvent exposure and reduced female fertility, but the evidence is inconclusive for male fertility. Objectives: To investigate the impact of solvent exposure on subfertility among families of male licensed pesticide applicators in the Agricultural Health Study cohort. Methods: The couples enrolled between 1993 and 1997. Cross-sectional questionnaire information on work tasks was used to assess exposure to solvents. The data were limited to couples ( wife aged less than 40 years) with an attempt at pregnancy in the last four years (n = 2112). Results: Twenty eight per cent of the couples were defined as subfertile ( not conceiving a pregnancy after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred). Adjusted subfertility odds ratios ( OR) for exposure to solvents were calculated with logistic regression. Female ( OR 1.42, 95% CI 1.15 to 1.75) and male exposure to solvents ( OR 1.21 ( 95% CI 0.93 to 1.57) for monthly exposure and 1.40 ( 95% CI 0.97 to 2.03) for daily or weekly exposure) were associated with subfertility. In farming, spouses may share or exchange jobs. To account for potential dual exposure, variables for parental exposure ( either parent exposed or both parents exposed) were also defined. Both were strongly associated with subfertility ( OR 1.62 ( 95% CI 1.20 to 2.17) and OR 2.10 ( 95% CI 1.22 to 3.60), respectively). Conclusions: Solvents may impair fertility of either gender, though the evidence for female effects is stronger than for male effects. C1 NIEHS, Epidemiol Branch, NIH, Dept Human Hlth Serv, Res Triangle Pk, NC 27709 USA. NCI, Occupat & Environm Epidemiol Branch, NIH, Dept Human Hlth Serv, Bethesda, MD 20892 USA. RP Sallmen, M (reprint author), Finnish Inst Occupat Hlth, Ctr Expertise Hlth & Work Abil, Topeliuksenkatu 41 aA, FI-00250 Helsinki, Finland. EM Markku.Sallmen@ttl.fi RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018 NR 32 TC 7 Z9 8 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUL PY 2006 VL 63 IS 7 BP 469 EP 475 DI 10.1136/oem.2005.021337 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 053QO UT WOS:000238320200007 PM 16698811 ER PT J AU Oh, J Diaz, T Wei, B Chang, H Noda, M Stetler-Stevenson, WG AF Oh, J. Diaz, T. Wei, B. Chang, H. Noda, M. Stetler-Stevenson, W. G. TI TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118 SO ONCOGENE LA English DT Article DE TIMP-2; RECK; Rac1; paxillin; Src ID CYSTEINE-RICH PROTEIN; FOCAL ADHESION KINASE; CELL LUNG-CANCER; NBT-II CELLS; TYROSINE PHOSPHORYLATION; CLINICAL-SIGNIFICANCE; TISSUE INHIBITORS; SIGNALING COMPLEX; KAZAL MOTIFS; SRC AB We previously demonstrated that TIMP-2 increases the association of Crk with C3G and via subsequent activation of Rap1 enhances the expression of RECK, a membrane-anchored MMP inhibitor. In the present study, we investigate the mechanism of how the TIMP-2 signal is transduced from the alpha 3 beta 1 integrin receptor to the Crk-C3G-Rap1 molecular complex. TIMP-2 treatment of human microvascular endothelial cells (hMVECs) increased the phosphorylation levels of Src at Tyr-527, the negative regulatory site, through enhanced association of Src with Csk. This results in the reduction of Src kinase activity and dephosphorylation of paxillin at Tyr-31/118, the target sites for Src kinase phosphorylation and also the binding sites for the downstream effector Crk. Such TIMP-2 effects accompany the disassembly of paxillin-Crk-DOCK180 molecular complex and, in turn, Rac1 inactivation. On the contrary, levels of paxillin-Crk-C3G complex formation are not reduced, rather slightly increased, which is consistent with our previous finding. Therefore, TIMP-2-mediated inhibition of Src kinase activity leads to the signaling switch from Rac1 to Rap1, thereby leading to enhanced RECK expression. C1 Korea Univ, Cellular Oncol Lab, Grad Sch Med, Ansan 425707, Gyeonggi Do, South Korea. NCI, Ctr Canc Res, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. Kyoto Univ, Dept Mol Oncol, Grad Sch Med, Kyoto, Japan. RP Oh, J (reprint author), Korea Univ, Cellular Oncol Lab, Grad Sch Med, 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 FU Intramural NIH HHS; NCI NIH HHS [Z01 SC009179, Z01 SC009179-17] NR 35 TC 30 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2006 VL 25 IS 30 BP 4230 EP 4234 DI 10.1038/sj.onc.1209444 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 063GA UT WOS:000239004800010 PM 16491114 ER PT J AU Chevalier, SA Meertens, L Pise-Masison, C Calattini, S Park, H Alhaj, AA Zhou, M Gessain, A Kashanchi, F Brady, JN Mahieux, R AF Chevalier, S. A. Meertens, L. Pise-Masison, C. Calattini, S. Park, H. Alhaj, A. A. Zhou, M. Gessain, A. Kashanchi, F. Brady, J. N. Mahieux, R. TI The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 tax rather than HTLV-2 Tax SO ONCOGENE LA English DT Article DE HTLV-3; tax; PDZ; CREB; NF-kappa B ID LONG TERMINAL REPEAT; LEUKEMIA-VIRUS; CENTRAL-AFRICA; MOLECULAR EPIDEMIOLOGY; 21-BASE-PAIR REPEATS; CERCOCEBUS-TORQUATUS; VIRAL REPLICATION; ESCHERICHIA-COLI; COACTIVATOR CBP; PAPIO-HAMADRYAS AB Human T-cell leukemia virus and simian T-cell leukemia virus ( STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator ( Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human T-cell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-kappa B pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations. C1 Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, F-75724 Paris 15, France. NCI, Virus Tumor Biol Sect, NIH, Bethesda, MD USA. George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC USA. RP Mahieux, R (reprint author), Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, 28 Rue Dr Roux, F-75724 Paris 15, France. EM rmahieux@pasteur.fr RI Meertens, Laurent/E-8043-2017 FU NIAID NIH HHS [AI43894, AI44357, AI13969] NR 63 TC 21 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2006 VL 25 IS 32 BP 4470 EP 4482 DI 10.1038/sj.onc.1209472 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 067TR UT WOS:000239326000010 PM 16532031 ER PT J AU Lowy, D AF Lowy, Douglas TI National cancer institute SO ONCOLOGY-NEW YORK LA English DT Letter C1 NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Lowy, D (reprint author), NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2006 VL 20 IS 8 BP 946 EP 946 PG 1 WC Oncology SC Oncology GA V44BG UT WOS:000202977600024 ER PT J AU Niederhuber, JE AF Niederhuber, John E. TI National cancer institute SO ONCOLOGY-NEW YORK LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Niederhuber, JE (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2006 VL 20 IS 8 BP 946 EP 946 PG 1 WC Oncology SC Oncology GA V44BG UT WOS:000202977600023 ER PT J AU Ivanovski, S Gronthos, S Shi, S Bartold, PM AF Ivanovski, S Gronthos, S Shi, S Bartold, PM TI Stem cells in the periodontal ligament SO ORAL DISEASES LA English DT Review DE fibroblasts; mesenchymal stem cells; periodontium ID HUMAN BONE-MARROW; HEALING FOLLOWING IMPLANTATION; CONNECTIVE-TISSUE; DENTAL-PULP; IN-VITRO; CEMENTOBLAST DIFFERENTIATION; AFFECTED ROOTS; ALVEOLAR BONE; POPULATIONS; MICE AB The ability to identify and manipulate stem cells has been a significant advancement in regenerative medicine and has contributed to the development of tissue engineering-based clinical therapies. Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques such as tissue engineering need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. One of the critical requirements for a tissue engineering approach is the delivery of ex vivo expanded progenitor populations or the mobilization of endogenous progenitor cells capable of proliferating and differentiating into the required tissues. By definition, stem cells fulfill these requirements and the recent identification of stem cells within the periodontal ligament represents a significant development in the progress toward predictable periodontal regeneration. In order to explore the importance of stem cells in periodontal wound healing and regeneration, this review will examine contemporary concepts in stem cell biology, the role of periodontal ligament progenitor cells in the regenerative process, recent developments in identifying periodontal stem cells and the clinical implications of these findings. C1 Univ Adelaide, Colgate Australian Clin Dent Res Ctr, Sch Dent, Adelaide, SA 5005, Australia. Univ Queensland, Sch Dent, Brisbane, Qld, Australia. Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Grp, Adelaide, SA 5000, Australia. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Bartold, PM (reprint author), Univ Adelaide, Colgate Australian Clin Dent Res Ctr, Sch Dent, Frome Rd, Adelaide, SA 5005, Australia. EM mark.bartold@adelaide.edu.au OI Bartold, Peter/0000-0002-5695-3877 NR 49 TC 102 Z9 110 U1 0 U2 23 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JUL PY 2006 VL 12 IS 4 BP 358 EP 363 DI 10.1111/j.1601-0825.2006.01253.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 054QP UT WOS:000238394000002 PM 16792719 ER PT J AU Gladen, B AF Gladen, Beth TI Questions regarding the basis of the analyses in study of the relationship of maternal concentrations of dichlorodiphenyl dichloroethylene (DDE) and initiation and duration of breast feeding: extrapolations of organochlorine levels for estimating exposure levels SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Letter C1 NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Gladen, B (reprint author), NIEHS, NIH, US Dept HHS, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM gladen@niehs.nih.gov FU Intramural NIH HHS NR 4 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2006 VL 20 IS 4 BP 360 EP 361 DI 10.1111/j.1365-3016.2006.00739.x PG 2 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 070OD UT WOS:000239531200010 PM 16879510 ER PT J AU Willson, DF Dean, JM Newth, C Pollack, M Anand, KJS Meert, K Carcillo, J Zimmerman, J Nicholson, C AF Willson, Douglas F. Dean, J. Michael Newth, Christopher Pollack, Murray Anand, K. J. S. Meert, Kathleen Carcillo, Joseph Zimmerman, Jerry Nicholson, Carol TI Collaborative Pediatric Critical Care Research Network (CPCCRN) SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE pediatric critical care; pediatric intensive care unit; clinical research; collaborative network; National Institutes of Health; National Institute of Child Health and Development ID RANDOMIZED CONTROLLED-TRIAL; HYPOXEMIC RESPIRATORY-FAILURE; LUNG SURFACTANT EXTRACT; INTENSIVE-CARE; CHILDREN; MORTALITY; RISK; OUTCOMES; INFANTS; INJURY AB Pediatric critical care was formally recognized as a separate subspecialty in pediatrics in 1987. Since that time the numbers of pediatric intensivists, pediatric intensive care units, and pediatric intensive care beds in the United States have increased dramatically. Research efforts have lagged behind, however, as this new discipline has struggled to identify the necessary time, funding, and other resources to pursue clinical and laboratory investigation. In April 2004, the National Center for Medical Rehabilitation Research of the National Institute for Child Health and Human Development issued a request for applications to establish the Collaborative Pediatric Critical Care Research Network (CPCCRN). The CPCCRN provides an infrastructure to pursue collaborative clinical trials and descriptive studies in pediatric critical care medicine. Six pediatric centers involving seven intensive care units and a data-coordinating center were identified through a competitive application process. Network goals include the support of collaborative clinical trials otherwise impracticable in single institutions and the establishment of a framework for developing the scientific basis for pediatric critical care practice. This article describes how the CPCCRN was established, its organization, and its goals and future plans. C1 Univ Virginia, Childrens Hosp, Charlottesville, VA 22903 USA. Univ Utah, Salt Lake City, UT 84112 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Seattle Childrens Hosp, Seattle, WA USA. NICHHD, Bethesda, MD 20892 USA. RP Willson, DF (reprint author), Univ Virginia, Childrens Hosp, Charlottesville, VA 22903 USA. OI Anand, Kanwaljeet/0000-0001-6498-1483 FU NICHD NIH HHS [UG1 HD050096] NR 43 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JUL PY 2006 VL 7 IS 4 BP 301 EP 307 DI 10.1097/01.PCC.0000227106.66902.4F PG 7 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 087ZN UT WOS:000240781400001 PM 16738501 ER PT J AU Ferris, ME Gipson, DS Kimmel, PL Eggers, PW AF Ferris, ME Gipson, DS Kimmel, PL Eggers, PW TI Trends in treatment and outcomes of survival of adolescents initiating end-stage renal disease care in the United States of America SO PEDIATRIC NEPHROLOGY LA English DT Article DE adolescent; end-stage renal disease; survival ID CHRONIC KIDNEY-DISEASE; TRANSPLANT RECIPIENTS; PEDIATRIC-PATIENTS; CHILDREN; DEATH; RISK; DIALYSIS; CHILDHOOD; MORTALITY; ADULTS AB This study characterizes treatment and outcome trends of adolescent patients initiating renal replacement therapy in the USA from 1978 to 2002. This is a retrospective analysis of data from the US Renal Data System (USRDS) of incident end-stage renal disease (ESRD) patients, ages 12 years through 19 years, initiating renal replacement therapy between 1978 and 2002. Survival analyses were conducted from either the first date of kidney failure or date of transplantation until death or 31 December 2002. The ESRD incidence per million adolescents increased from 17.6 in 1978 to 26.0 in 1990, with no change in incidence in the ensuing 12 years. Incidence was slightly higher among males than females and was twice as great in black than in white populations. The major cause of ESRD was glomerulonephritis followed by cystic/congenital diseases and focal segmental glomerulosclerosis (FSGS). Incidence increased with age, from 13.0 per million for children aged 13 years to 32.6 per million for 19 year olds. Three-quarters of all adolescent patients received at least one transplant, and one-fifth of patients received two or more transplants. Ten percent of incident adolescent patients received a preemptive transplant. The 10-year survival rate was lowest in the 1978-1982 incident cohort (77.6%) and improved to approximately 80% for later cohorts. Survival was better for younger adolescents, transplant recipients, preemptive transplant recipients, males, Caucasian, and Asian patients. The primary mode of renal replacement therapy is transplantation in most adolescent ESRD patients. The 80% 10-year survival rate for adolescent-onset ESRD is very good when compared with adult-onset ESRD. However, this represents a 30-fold increase in mortality compared to the general US adolescent population. C1 Univ N Carolina, Div Nephrol & Hypertens, Chapel Hill, NC 27599 USA. NIDDK, Div Kidney Urol & Hematol Dis, NIH, Chapel Hill, NC USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Ferris, ME (reprint author), Univ N Carolina, Div Nephrol & Hypertens, Chapel Hill, NC 27599 USA. EM Maria_Ferris@med.unc.edu NR 31 TC 48 Z9 49 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUL PY 2006 VL 21 IS 7 BP 1020 EP 1026 DI 10.1007/s00467-006-0059-9 PG 7 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 053GI UT WOS:000238293200020 PM 16773416 ER PT J AU Foca, M Moye, J Chu, C Matthews, Y Rich, K Handelsman, E Luzuriaga, K Paul, M Diaz, C AF Foca, M Moye, J Chu, C Matthews, Y Rich, K Handelsman, E Luzuriaga, K Paul, M Diaz, C CA Women Infants Transmission Study TI Gender differences in lymphocyte populations, plasma HIV RNA levels, and disease progression in a cohort of children born to women infected with HIV SO PEDIATRICS LA English DT Article DE HIV; gender ID ACTIVE ANTIRETROVIRAL THERAPY; VIRAL LOAD; SEX-DIFFERENCES; CELL COUNTS; SURVIVAL DIFFERENCES; CLINICAL OUTCOMES; AIDS; ADOLESCENTS; MEN; SUBSETS AB OBJECTIVE. We sought to document gender differences in lymphocyte subsets and plasma RNA levels in a pediatric cohort with presumed minimal hormonal differences ( on the basis of age). METHODS. Blood samples from antiretroviral therapy-treated, HIV-infected children ( n = 158) and HIV-uninfected children ( n = 1801) who were enrolled in the Women and Infants Transmission Study were analyzed at specified study intervals with consensus protocols, and various parameters were compared. RESULTS. Antiretroviral therapy-treated, HIV-infected female children had, on average, 0.38 log(10) copies per mL lower plasma RNA levels than did their male counterparts, but lymphocyte differences were not noted in this cohort. Despite their higher plasma RNA level, a greater proportion of male children survived through 8 years of age. There were no gender differences with respect to the age of diagnosis of HIV, time to antiretroviral therapy after diagnosis of HIV, or type of antiretroviral therapy. Lymphocyte differences were noted for uninfected children. CONCLUSIONS. Plasma RNA levels differed among antiretroviral therapy-treated, HIV-infected children according to gender, in a manner similar to that noted in previous pediatric and adult studies. Lymphocyte subsets varied according to gender in a cohort of HIV-exposed but uninfected children. Most importantly, overall mortality rates for this cohort differed according to gender. C1 Columbia Univ, Dept Pediat, New York, NY 10027 USA. NICHHD, Bethesda, MD 20892 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Illinois, Dept Pediat, Chicago, IL USA. SUNY, Dept Pediat, Brooklyn, NY USA. Univ Massachusetts, Dept Pediat, Worcester, MA 01605 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Puerto Rico, Dept Pediat, San Juan, PR 00936 USA. RP Foca, M (reprint author), Morgan Stanley Childrens Hosp, Dept Pediat, Div Infect Dis, 622 W 168th St,VC-1 E,Room 119H, New York, NY 10032 USA. EM mdf10@columbia.edu OI moye, john/0000-0001-9976-8586 FU NCRR NIH HHS [RR000188, RR000645]; NIAID NIH HHS [N01 AI 085339, 1 U01 AI 050274-01, U01 AI 034841, U01 AI 034858]; NICHD NIH HHS [U01 HD 041983, U01 HD 036117]; NIDA NIH HHS [9U01 DA 015054, U01 DA 015053] NR 34 TC 15 Z9 15 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2006 VL 118 IS 1 BP 146 EP 155 DI 10.1542/peds.2005-0294 PG 10 WC Pediatrics SC Pediatrics GA 059II UT WOS:000238726100018 PM 16818560 ER PT J AU Vohr, BR Poindexter, BB Dusick, AM McKinley, LT Wright, LL Langer, JC Poole, WK AF Vohr, BR Poindexter, BB Dusick, AM McKinley, LT Wright, LL Langer, JC Poole, WK CA NICHD Neonatal Res Network TI Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age SO PEDIATRICS LA English DT Article DE human milk; extremely low birth weight; Bayley; outcomes ID POLYUNSATURATED FATTY-ACIDS; VISUAL-ACUITY DEVELOPMENT; PRETERM INFANTS; INTELLIGENCE QUOTIENT; RANDOMIZED-TRIAL; MATERNAL MILK; TERM INFANTS; FORMULA; HEALTHY; SUPPLEMENTATION AB OBJECTIVE. Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously. METHODS. Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months' corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months' corrected age were assessed. RESULTS. There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 +/- 9 days. Infants in the breast milk group began to ingest non-breast milk formula later (22.8 vs 7.3 days) compared with the non breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non-breast milk groups (29.0 +/- 18 vs 27.4 +/- 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non-breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (<=$20000), or had higher parity were less likely to provide breast milk feeds. The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age, maternal education, marital status, race/ethnicity, and the other standard covariates. Children in the breast milk group were more likely to have a Bayley Mental Development Index >= 85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization < 1 year), only the values for the > 80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyes, every 10-mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 x 0.53, or 5.3 points. CONCLUSIONS. An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services. The societal implications of a 5-point potential difference (one third of an SD) in IQ are substantial. The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services. C1 Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. NICHHD, Ctr Res Mothers & Children, Rockville, MD USA. RTI Int, Res Triangle Pk, NC USA. RP Vohr, BR (reprint author), Brown Univ, Women & Infants Hosp, 101 Dudley St, Providence, RI 02905 USA. EM Betty_Vohr@brown.edu FU NCRR NIH HHS [M01 RR 00070, M01 RR 00750, M01 RR 06022, M01 RR 08084, M01 RR00997]; NICHD NIH HHS [U10 HD21373, U01 HD36790, U10 HD21364, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40689] NR 57 TC 175 Z9 185 U1 5 U2 33 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2006 VL 118 IS 1 BP E115 EP E123 DI 10.1542/peds.2005-2382 PG 9 WC Pediatrics SC Pediatrics GA 059II UT WOS:000238726100078 PM 16818526 ER PT J AU Xiong, CY O'Keefe, BR Byrd, RA McMahon, JB AF Xiong, CY O'Keefe, BR Byrd, RA McMahon, JB TI Potent anti-HIV activity of scytovirin domain 1 peptide SO PEPTIDES LA English DT Article DE scytovirin; SD1; SD2; microbicide; HIV; anti-viral ID CYANOBACTERIUM SCYTONEMA-VARIUM; CYANOVIRIN-N; INACTIVATING PROTEIN; ENTRY; ENFUVIRTIDE; INHIBITOR; ENVELOPE; DISCOVERY; GP120 AB Scytovirin (SVN) is a novel anti-HIV protein isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium. SVN contains two apparent domains, one comprising amino acids 1-48 and the second stretching from amino acids 49 to 95. These two domains display significant homology to each other and a similar pattern of disulfide bonds. Two DNA constructs encoding scytovirin 1-48 (Cys7Ser) (SD1) and 49-95 (Cys55Ser) (SD2) were constructed, and expressed in E. coli, with thioredoxin fused to their N-terminus. Purified recombinant products were tested for binding activities with the HIV surface envelope glycoproteins gp120 and gp41. Whole cell anti-HIV data showed that SDI had similar anti-HIV activity to the full-length SVN, whereas SD2 had significantly less anti-HIV activity. Further deletion mutants of the SD1 domain (SVN(3-45)Cys7Ser, SVN(6-45)Cys7Ser, SVN(11-45)Cys7Ser) showed that the N-terminal residues are necessary for full anti-HIV activity of SDI and that an eight amino acid deletion from the C-terminus (SVN(1-40)Cys7Ser) had a significant effect, decreasing the anti-HIV activity of SDI by approximately five-fold. Published by Elsevier Inc. C1 NCI, Mol Targets Dev Program, NIH, Frederick, MD 21702 USA. NCI, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. RP O'Keefe, BR (reprint author), NCI, Mol Targets Dev Program, NIH, Bldg 562-Rm 201, Frederick, MD 21702 USA. EM okeefe@ncifcrf.gov RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 FU Intramural NIH HHS NR 20 TC 17 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL PY 2006 VL 27 IS 7 BP 1668 EP 1675 DI 10.1016/j.peptides.2006.03.018 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 060CV UT WOS:000238780300011 PM 16647158 ER PT J AU Blair, KS Morton, J Leonard, A Blair, RJR AF Blair, K. S. Morton, J. Leonard, A. Blair, R. J. R. TI Impaired decision-making on the basis of both reward and punishment information in individuals with psychopathy SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE psychopathy; decision-making; reward; punishment ID MODULATION; CHECKLIST; EMOTION AB In this study, we examined decision-making to rewarding or punishing stimuli in individuals with psychopathy (n = 21) and comparison individuals (n = 19) using the Differential Reward/Punishment Learning Task. In this task, the participant chooses between two objects associated with different levels of reward or punishment. Thus, response choice indexes not only reward/punishment sensitivity but also sensitivity to reward/punishment level according to inter-stimulus reinforcement distance. Individuals with psychopathy showed significant impairment when choosing between objects associated with differential levels of reward but also significantly greater impairment when choosing between objects associated with differential levels of punishment. However, the two groups were comparably affected by inter-stimulus reinforcement distance. The results are discussed with reference to current models of psychopathy. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Inst Mental Hlth, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London, England. HM Prison Wormwood Scrubs, Dept Psychol, London, England. RP Blair, RJR (reprint author), Natl Inst Mental Hlth, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv,NIH, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 24 TC 32 Z9 32 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD JUL PY 2006 VL 41 IS 1 BP 155 EP 165 DI 10.1016/j.paid.2005.11.031 PG 11 WC Psychology, Social SC Psychology GA 058JZ UT WOS:000238662600014 ER PT J AU Oz, M AF Oz, M TI Receptor-independent actions of cannabinoids on cell membranes: Focus on endocannabinoids SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE endocannabinoids; cannabinoids; ion channels; fatty acids; arachidonic acid; prostaglandins ID NICOTINIC ACETYLCHOLINE-RECEPTOR; POLYUNSATURATED FATTY-ACIDS; SMOOTH-MUSCLE-CELLS; ROOT GANGLION NEURONS; BOVINE SERUM-ALBUMIN; T-TUBULE MEMBRANES; VOLTAGE-GATED K+; GAP JUNCTIONAL COMMUNICATION; HUMAN NEUROGLIOMA CELLS; DEPENDENT CA2+ FLUXES AB Cannabinoids are a structurally diverse group of mostly lipophilic molecules that bind to cannabinoid receptors. In fact, endogenous cannabinoids (endocannabinoids) are a class of signaling lipids consisting of amides and esters of long-chain polyunsaturated fatty acids. They are synthesized from lipid precursors in plasma membranes via Ca2+ or G-protein-dependent processes and exhibit cannabinoid-like actions by binding to cannabinoid receptors. However, endocannabinoids can produce effects that are not mediated by these receptors. In pharmacologically relevant concentrations, endocannabinoids modulate the functional properties of voltage-gated ion channels including Ca2+ channels, Na+ channels, various types of (+) channels, and ligand-gated ion channels such as serotonin type 3, nicotinic acetylcholine, and glycine receptors. In addition, modulatory effects of endocannabinoids on other ion-transporting membrane proteins such as transient potential receptor-class channels, gap junctions and transporters for neurotransmitters have also been demonstrated. Furthermore, functional properties of G-protein-coupled receptors for different types of neurotransmitters and neuropeptides are altered by direct actions of endocannabinoids. Although the mechanisms of these effects are currently not clear, it is likely that these direct actions of endocannabinoids are due to their lipophilic structures. These findings indicate that additional molecular targets for endocannabinoids exist and that these targets may represent novel sites for cannabinoids to alter either the excitability of the neurons or the response of the neuronal systems. This review focuses on the results of recent studies indicating that beyond their receptor-mediated effects, endocannabinoids alter the functions of ion channels and other integral membrane proteins directly. Published by Elsevier Inc. C1 NIDA, DHHS, Intramural Res Program, Cellular Neurobiol Branch,NIH, Baltimore, MD 21224 USA. RP Oz, M (reprint author), NIDA, DHHS, Intramural Res Program, Cellular Neurobiol Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 394 TC 100 Z9 102 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JUL PY 2006 VL 111 IS 1 BP 114 EP 144 DI 10.1016/j.pharmthera.2005.09.009 PG 31 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 053GT UT WOS:000238294300007 PM 16584786 ER PT J AU Skirpan, AL Dowd, PE Sijacic, P Jaworski, CJ Gilroy, S Kao, TH AF Skirpan, Andrea L. Dowd, Peter E. Sijacic, Paja Jaworski, Cynthia J. Gilroy, Simon Kao, Teh-hui TI Identification and characterization of PiORP1, a Petunia oxysterol-binding-protein related protein involved in receptor-kinase mediated signaling in pollen, and analysis of the ORP gene family in Arabidopsis SO PLANT MOLECULAR BIOLOGY LA English DT Article DE oxysterol-binding-protein related proteins; pollen; pollen tube; receptor-like kinase ID TUBE GROWTH; GOLGI LOCALIZATION; YEAST; OSBP; HOMOLOGY; INFLATA; PATHWAY; CELLS; TRANSPORT; APOPTOSIS AB Oxysterol-binding proteins (OSBPs) and oxysterol-binding-protein related proteins (ORPs) are encoded by most eukaryotic genomes examined to date; however, they have not yet been characterized in plants. Here we report the identification and characterization of PiORP1, an ORP of Petunia inflata that interacts with the cytoplasmic kinase domain of a receptor-like kinase, named PRK1, of P. inflata. PiORP1 is phosphorylated by PRK1 in vitro and therefore may be involved in PRK1 signaling during pollen development and growth. RNA gel blot analysis showed that PiORP1 and PRK1 had very similar expression patterns in developing pollen, mature pollen and pollen tubes. GFP fusion proteins of PiORP1 localized in the plasma membrane of pollen tubes at distinct foci and its PH domain alone was sufficient to mediate this localization. The sequence for the oxysterol-binding domain of PiORP1 was used to search the genome of Arabidopsis; 12 ORPs were identified and phylogenetic analysis revealed that they fell into two distinct clades, consistent with the ORPs of other eukaryotes. RT-PCR analysis showed that all 12 Arabidopsis ORPs were expressed; 10 were expressed in most of the tissues examined under normal growth conditions, but only three were expressed in pollen. C1 Penn State Univ, Althouse Lab 403, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. Penn State Univ, Integrat Biosci Grad Program, University Pk, PA 16802 USA. NEI, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. RP Kao, TH (reprint author), Penn State Univ, Althouse Lab 403, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. EM txk3@psu.edu OI Gilroy, Simon/0000-0001-9597-6839 NR 45 TC 18 Z9 31 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD JUL PY 2006 VL 61 IS 4-5 BP 553 EP 565 DI 10.1007/s11103-006-0030-y PG 13 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 070UT UT WOS:000239551300001 PM 16897474 ER PT J AU Srivastava, P Nath, N Deb, JK AF Srivastava, P Nath, N Deb, JK TI Characterization of broad host range cryptic plasmid pCR1 from Corynebacterium renale SO PLASMID LA English DT Article DE Corynebacterium renale; cryptic plasmid; rolling circle mode ID DNA-POLYMERASE-I; ESCHERICHIA-COLI; BREVIBACTERIUM-LACTOFERMENTUM; BACILLUS-SUBTILIS; GLUTAMICUM; REPLICATION; PGA1; REPLICON; CLONING; REGION AB Plasmid pCR1 is a cryptic plasmid harboured by Corynebacterium renale. It is the smallest corynebacterial plasmid known to date. Although its natural host is animal corynebacteria, it can replicate in several strains of soil corynebacteria. It can also replicate in Escherichia coli, in which it is stably maintained. The copy number of pCR1 in this host is higher than that of pUC19, with which it shows unidirectional incompatibility. It is also incompatible with pBK2, a plasmid bearing the common corynebacterial replicon pBL1. Its size is 1488 bp, as revealed by DNA sequencing. A total of eight open reading frames (ORF) were detected in this plasmid, the largest of which codes for a putative Rep protein of predicted molecular mass of 21 kDa. The plasmid pCR1 can be mobilized by the plasmid R6K from E. coli to other corynebacteria. Sequence analysis revealed the presence of an oriT homologous to that of R64. An E coli plasmid pKL1 shows more than. 90% identity with pCR1. Like many coryenbacierial plasmids, pCR1 also replicates by rolling circle mode. (c) 2006 Elsevier Inc. All rights reserved. C1 Indian Inst Technol, Dept Biochem Engn & Biotechnol, New Delhi 110016, India. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. New York Inst Technol, Sch Behav Hlth & Life Sci, New York, NY 10023 USA. RP Deb, JK (reprint author), Indian Inst Technol, Dept Biochem Engn & Biotechnol, New Delhi 110016, India. EM jahardeb@yahoo.co.in NR 35 TC 8 Z9 9 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD JUL PY 2006 VL 56 IS 1 BP 24 EP 34 DI 10.1016/j.plasmid.2006.01.003 PG 11 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 053AT UT WOS:000238276600003 PM 16545871 ER PT J AU Meier-Schellersheim, M Xu, XH Angermann, B Kunkel, EJ Jin, T Germain, RN AF Meier-Schellersheim, Martin Xu, Xuehua Angermann, Bastian Kunkel, Eric J. Jin, Tian Germain, Ronald N. TI Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; SIGNAL-TRANSDUCTION; CHEMOTACTIC CELLS; GROWTH-FACTOR; LEADING-EDGE; BETA-GAMMA; PROTEIN; PTEN; ACTIVATION; DICTYOSTELIUM AB The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential activation/deactivation of membrane-bound and cytosolic components. As such, it provides particularly interesting challenges for a combined computational and experimental analysis. We developed a novel detailed molecular signaling model that, when used to simulate the response to the attractant cyclic adenosine monophosphate (cAMP), made nontrivial predictions about Dictyostelium chemosensing. These predictions, including the unexpected existence of spatially asymmetrical, multiphasic, cyclic adenosine monophosphate-induced PTEN translocation and phosphatidylinositol-(3,4,5) P-3 generation, were experimentally verified by quantitative single-cell microscopy leading us to propose significant modifications to the current standard model for chemoattractant-induced biochemical polarization in this organism. Key to this successful modeling effort was the use of "Simmune,'' a new software package that supports the facile development and testing of detailed computational representations of cellular behavior. An intuitive interface allows user definition of complex signaling networks based on the definition of specific molecular binding site interactions and the subcellular localization of molecules. It automatically translates such inputs into spatially resolved simulations and dynamic graphical representations of the resulting signaling network that can be explored in a manner that closely parallels wet lab experimental procedures. These features of Simmune were critical to the model development and analysis presented here and are likely to be useful in the computational investigation of many aspects of cell biology. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD USA. NIAID, Program Syst Immunol, Immunol Lab, NIH, Bethesda, MD USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. BioSeek Inc, Burlingame, CA USA. Univ Hamburg, Fac Math & Nat Sci, Inst Theoret Phys, Hamburg, Germany. RP Meier-Schellersheim, M (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD USA. EM mms@niaid.nih.gov; rgermain@niaid.nih.gov OI xu, xuehua/0000-0002-3863-9593 FU Intramural NIH HHS NR 43 TC 79 Z9 81 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUL PY 2006 VL 2 IS 7 BP 710 EP 724 AR e82 DI 10.1371/journal.pcbi.0020082 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 070BA UT WOS:000239494100006 PM 16854213 ER PT J AU Svartman, M Stone, G Stanyon, R AF Svartman, Marta Stone, Gary Stanyon, Roscoe TI The ancestral Eutherian karyotype is present in Xenarthra SO PLOS GENETICS LA English DT Article ID PLACENTAL MAMMAL RADIATION; HUMAN-CHROMOSOMES; ZOO-FISH; MITOCHONDRIAL; ANTEATERS; PHYLOGENETICS; AFROTHERIA; ARMADILLOS; EVOLUTION; HOMOLOGS AB Molecular studies have led recently to the proposal of a new super-ordinal arrangement of the 18 extant Eutherian orders. From the four proposed super-orders, Afrotheria and Xenarthra were considered the most basal. Chromosome-painting studies with human probes in these two mammalian groups are thus key in the quest to establish the ancestral Eutherian karyotype. Although a reasonable amount of chromosome-painting data with human probes have already been obtained for Afrotheria, no Xenarthra species has been thoroughly analyzed with this approach. We hybridized human chromosome probes to metaphases of species (Dasypus novemcinctus, Tamandua tetradactyla, and Choloepus hoffmanii) representing three of the four Xenarthra families. Our data allowed us to review the current hypotheses for the ancestral Eutherian karyotype, which range from 2n = 44 to 2n = 48. One of the species studied, the two-toed sloth C. hoffmanii (2n = 50), showed a chromosome complement strikingly similar to the proposed 2n = 48 ancestral Eutherian karyotype, strongly reinforcing it. C1 NCI, Comparat Mol Cytogenet Core, Bethesda, MD 20892 USA. RP Svartman, M (reprint author), NCI, Comparat Mol Cytogenet Core, Bethesda, MD 20892 USA. EM svartmanm@hotmail.com RI Svartman, Marta/B-4528-2008; OI Svartman, Marta/0000-0003-3239-1862; Stanyon, Roscoe/0000-0002-7229-1092 FU Intramural NIH HHS NR 27 TC 19 Z9 21 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2006 VL 2 IS 7 BP 1006 EP 1011 AR e109 DI 10.1371/journal.pgen.0020109 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 070BH UT WOS:000239494800011 PM 16848642 ER PT J AU Zahn, JM Sonu, R Vogel, H Crane, E Mazan-Mamczarz, K Rabkin, R Davis, RW Becker, KG Owen, AB Kim, SK AF Zahn, Jacob M. Sonu, Rebecca Vogel, Hannes Crane, Emily Mazan-Mamczarz, Krystyna Rabkin, Ralph Davis, Ronald W. Becker, Kevin G. Owen, Art B. Kim, Stuart K. TI Transcriptional profiling of aging in human muscle reveals a common aging signature SO PLOS GENETICS LA English DT Article ID GENE-EXPRESSION PROFILE; SYSTEMATIC RNAI SCREEN; C-ELEGANS; SIALYLTRANSFERASE ACTIVITY; DROSOPHILA-MELANOGASTER; ALZHEIMERS-DISEASE; LONGEVITY; AGE; PATTERNS; BRAIN AB We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome), while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain). We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species. C1 Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Dept Biochem, Stanford, CA 94305 USA. NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Kim, SK (reprint author), Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA. EM kim@cmgm.stanford.edu OI Vogel, Otto Hannes/0000-0002-0960-3508; Becker, Kevin/0000-0002-6794-6656 FU NIA NIH HHS [R01 AG025941] NR 41 TC 186 Z9 193 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2006 VL 2 IS 7 BP 1058 EP 1069 AR e115 DI 10.1371/journal.pgen.0020115 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 070BH UT WOS:000239494800016 PM 16789832 ER PT J AU Emanuel, EJ Lemmens, T Elliot, C AF Emanuel, Ezekiel J. Lemmens, Trudo Elliot, Carl TI Should society allow research ethics boards to be run as for-profit enterprises? SO PLOS MEDICINE LA English DT Editorial Material ID CONFLICT-OF-INTEREST; CLINICAL INVESTIGATORS; PARTICIPANTS AB Background to the debate: An important mechanism for protecting human research participants is the prior approval of a clinical study by a research ethics board, known in the United States as an institutional review board (IRB). Traditionally, IRBs have been run by volunteer committees of scientists and clinicians working in the academic medical centers where the studies they review are being carried out. However, for-profit organizations are increasingly being hired to conduct ethics reviews. Proponents of for-profit IRBs argue that these IRBs are just as capable as academic IRBs at providing high-quality ethics reviews. Critics argue that for-profit IRBs have a conflict of interest because they generate their income from clients who have a direct financial interest in obtaining approval. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Univ Toronto, Fac Law, Toronto, ON M5S 1A1, Canada. Univ Minnesota, Ctr Bioeth, Minneapolis, MN 55455 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM EEmanuel@cc.nih.gov; Trudo.lemmens@utoronto.ca; ellio023@tc.umn.edu NR 17 TC 15 Z9 15 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JUL PY 2006 VL 3 IS 7 BP 941 EP 944 AR e309 DI 10.1371/journal.pmed.0030309 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 070AS UT WOS:000239493300002 PM 16848618 ER PT J AU Fowler, T Steakley, C Garcia, AR Kwok, J Bennett, LM AF Fowler, Tisha Steakley, Caryn Garcia, A. Roland Kwok, Jennifer Bennett, L. Michelle TI Reducing disparities in the burden of cancer: The role of patient navigators SO PLOS MEDICINE LA English DT Editorial Material C1 NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Bennett, LM (reprint author), NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM LMBennett@nih.gov FU Intramural NIH HHS NR 10 TC 24 Z9 24 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JUL PY 2006 VL 3 IS 7 BP 974 EP 976 AR e193 DI 10.1371/journal.pmed.0030193 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 070AS UT WOS:000239493300012 PM 16805649 ER PT J AU Buck, CB Thompson, CD Roberts, JN Muller, M Lowy, DR Schiller, JT AF Buck, Christopher B. Thompson, Cynthia D. Roberts, Jeffrey N. Mueller, Martin Lowy, Douglas R. Schiller, John T. TI Carrageenan is a potent inhibitor of papillomavirus infection SO PLOS PATHOGENS LA English DT Article AB Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate-independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs. C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Deutsch Krebsforschungszentrum, Forschungsschwerpunkt Angew Tumorvirol, D-6900 Heidelberg, Germany. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS NR 2 TC 162 Z9 169 U1 1 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2006 VL 2 IS 7 BP 671 EP 680 AR e69 DI 10.1371/journal.ppat.0020069 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA V42VJ UT WOS:000202894700005 PM 16839203 ER PT J AU Ebihara, H Takada, A Kobasa, D Jones, S Neumann, G Theriault, S Bray, M Feldmann, H Kawaoka, Y AF Ebihara, Hideki Takada, Ayato Kobasa, Darwyn Jones, Steven Neumann, Gabriele Theriault, Steven Bray, Mike Feldmann, Heinz Kawaoka, Yoshihiro TI Molecular determinants of Ebola virus virulence in mice SO PLOS PATHOGENS LA English DT Article AB Zaire ebolavirus (ZEBOV) causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. The molecular basis for the extreme virulence of ZEBOV remains elusive. While adult mice resist ZEBOV infection, the Mayinga strain of the virus has been adapted to cause lethal infection in these animals. To understand the pathogenesis underlying the extreme virulence of Ebola virus ( EBOV), here we identified the mutations responsible for the acquisition of the high virulence of the adapted Mayinga strain in mice, by using reverse genetics. We found that mutations in viral protein 24 and in the nucleoprotein were primarily responsible for the acquisition of high virulence. Moreover, the role of these proteins in virulence correlated with their ability to evade type I interferon-stimulated antiviral responses. These findings suggest a critical role for overcoming the interferon-induced antiviral state in the pathogenicity of EBOV and offer new insights into the pathogenesis of EBOV infection. C1 Univ Tokyo, Inst Med Sci, Tokyo, Japan. Publ Hlth Agcy Canada, Special Pathogens Prorgram, Natl Microbiol Lab, Winnipeg, MB, Canada. Hokkaido Univ, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan. Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. Univ Wisconsin, Dept Pathobiol Sci, Sch Vet Med, Madison, WI USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. Int Res Ctr Infect Dis, Tokyo, Japan. RP Kawaoka, Y (reprint author), Univ Tokyo, Inst Med Sci, 4-6-1 Shirokanedai, Tokyo, Japan. EM kawaokay@svm.vetmed.wisc.edu RI Takada, Ayato/A-6679-2012 FU NIAID NIH HHS [1-U54-AI-057153, U54 AI057153] NR 1 TC 95 Z9 101 U1 3 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2006 VL 2 IS 7 BP 705 EP 711 AR e73 DI 10.1371/journal.ppat.0020073 PG 7 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA V42VJ UT WOS:000202894700008 PM 16848640 ER PT J AU Fodor, E Ginsburg, A AF Fodor, E Ginsburg, A TI Specific DNA binding by the homeodomain N-kx2.5(C56S): Detection of impaired DNA or unfolded protein by isothermal titration calorimetry SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE homeodomain; protein; duplex DNA stability; heat capacity change ID VND/NK-2 HOMEODOMAIN; NKX2.5 HOMEODOMAIN; SEQUENCE; DROSOPHILA; MUTATIONS; GENE; ENERGETICS; STABILITY; THERMODYNAMICS; HEART AB Titrations of specific 18-bp duplex DNA with the cardiac-specific homeodomain Nkx2.5(C56S) have utilized an ultrasensitive isothermal titration calorimeter (ITC). As the free DNA nears depletion, we observe large apparent decreases in the binding enthalpy when the DNA is impaired or when the temperature is sufficiently high to produce some unfolding of the free protein. Either effect can be attributed to refolding of the biopolymer that occurs as a result of stabilization due to the large favorable change in free energy on the homeodomain binding to DNA (-49.4 kJ/mol at 298 K). In either case, thermodynamic parameters obtained in such ITC experiments are unreliable. By using a lower temperature (85 vs. 95 degrees C) during the annealing of complementary DNA strands, damage of the 18-bp duplex DNA (T-m = 72 degrees C) is avoided, and titrations with the homeodomain are normal at temperatures from 10 to 40 degrees C when > 95% of the protein is folded. Under the latter conditions, the heat capacity plot is linear with a Delta C-p value of -0.80 +/- 0.03 kJ K-1 mol(-1), which is more negative than that calculated from the burial of solvent accessible surface areas (-0.64 +/- 0.05 kJ K-1 mol(-1)), consistent with water structures being at the protein-DNA interfaces. C1 NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Ginsburg, A (reprint author), NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bldg 50,Room 2339, Bethesda, MD 20892 USA. EM ginsbura@nhlbi.nih.gov NR 31 TC 2 Z9 3 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUL 1 PY 2006 VL 64 IS 1 BP 13 EP 18 DI 10.1002/prot.20960 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 048GO UT WOS:000237935800002 PM 16555308 ER PT J AU de Torre, C Ying, SX Munson, PJ Meduri, GU Suffredini, AF AF de Torre, Carlos Ying, Sai-Xia Munson, Peter J. Meduri, G. Umberto Suffredini, Anthony F. TI Proteomic analysis of inflammatory biomarkers in bronchoalveolar lavage SO PROTEOMICS LA English DT Article DE apolipoprotein A1; calgranulin; human bronchoalveolar lavage fluid proteins; SELDI-TOF/MS ID APOLIPOPROTEIN-A-I; 2-DIMENSIONAL ELECTROPHORESIS; FLUID PROTEINS; OVARIAN-CANCER; PEPTIDE LL-37; SERUM; LUNG; LIPOPOLYSACCHARIDE; IDENTIFICATION; LIPOPROTEINS AB To assess markers of lung inflammation, we used SELDI-TOF and 2-DE to study changes in bronchoalveolar lavage (BAL) protein in 33 subjects challenged with local bronchial lung endotoxin and saline and in 11 patients with acute respiratory distress syndrome (ARDS). Differences in the SELDI-TOF spectra were assessed by t-test after baseline subtraction, normalization to total ion current and alignment by m/z calibration. The temporal changes in acute inflammatory BAL (6, 24 and 48 h following endotoxin challenge) on hydrophobic binding chip surfaces revealed the differential presence of proteins of 9, 14, 18 and 28 kDa (all p < 0.001) in the inflammatory BAL. This differential pattern was also found in the ARDS BAL. Principal component analysis of the entire SELDI-TOF spectra separated normal BAL, experimental and clinical lung inflammation supporting the notion of a distinctive protein pattern associated with acute lung inflammation. An analysis of the hydrophobic fraction of the inflammatory BAL using 2-DE, identified increased levels of apolipoprotein A1, and S100 calcium-binding proteins A8 and A9 in the inflammatory BAL. This pattern was also found in ARDS BAL after immunoblot analysis. These approaches will be useful to improve current methods of monitoring lung inflammation and to identify new therapeutic targets. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. RP Suffredini, AF (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10,Room 2C145, Bethesda, MD 20892 USA. EM asuffredini@cc.nih.gov NR 44 TC 51 Z9 51 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JUL PY 2006 VL 6 IS 13 BP 3949 EP 3957 DI 10.1002/pmic.200500693 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063UN UT WOS:000239045500022 PM 16767788 ER PT J AU Hood, BL Conrads, TP Veenstra, TD AF Hood, Brian L. Conrads, Thomas P. Veenstra, Timothy D. TI Mass spectrometric analysis of formalin-fixed paraffin-embedded tissue: Unlocking the proteome within SO PROTEOMICS LA English DT Review DE cancer biomarkers; formalin-fixed paraffin-embedded tissue; mass spectrometry; proteome; tissue microdissection ID POLYMERASE-CHAIN-REACTION; YEAST PROTEOME; CANCER; IDENTIFICATION; DISCOVERY; PEPTIDE; MS/MS AB The predominance of tissues stored worldwide in hospitals and clinical laboratories exist in formalin-fixed paraffin-embedded (FFPE) blocks that are generated by simple and well-established protocols. Although generation of FFPE tissues has facilitated their characterization by such techniques as histopathology, they have proven refractory to biomarker discovery investigations using state-of-the-art MS-based proteomic methodologies. Very recently new methods have been developed that enable proteins extracted from FFPE tissues to be analyzed by MS. This review will highlight and discuss those efforts that have led to this exciting recent progress. Although these developments are quite new, the ability to conduct MS-based proteomic analyses of FFPE tissues opens heretofore intractable clinical samples for discovery-based biomarker research. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 34 TC 59 Z9 61 U1 1 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JUL PY 2006 VL 6 IS 14 BP 4106 EP 4114 DI 10.1002/pmic.200600016 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 068FR UT WOS:000239358600014 PM 16800036 ER PT J AU Goldstein, RB Olfson, M Wickramaratne, PJ Wolk, SI AF Goldstein, RB Olfson, M Wickramaratne, PJ Wolk, SI TI Use of outpatient mental health services by depressed and anxious children as they grow up SO PSYCHIATRIC SERVICES LA English DT Article ID COMORBIDITY SURVEY REPLICATION; GENERALIZED ANXIETY DISORDER; INITIAL TREATMENT CONTACT; SCHOOL-AGE-CHILDREN; UNITED-STATES; HELP-SEEKING; PANIC DISORDER; 1ST ONSET; PSYCHIATRIC-DIAGNOSIS; MAJOR DEPRESSION AB Objective: Childhood-onset psychiatric disorders can be persistent and impairing but often go untreated. Affected individuals' treatment utilization into adulthood is not well understood. A 15-year follow-up of depressed, anxious, and never mentally ill children (control group) examined need, predisposing, and enabling factors associated with use of outpatient mental health care into early adulthood. Methods: Between 1977 and 1985, a total of 315 children and adolescents were ascertained. Their psychiatric status and treatment utilization into adulthood were reassessed between 1991 and 1997 by clinicians blind to their childhood diagnoses. Results: Respondents ascertained for depression demonstrated 13-fold, and those ascertained for anxiety demonstrated six-fold, greater odds of any treatment compared with controls. Among utilizers, childhood depression conferred 14-fold, and childhood anxiety, 23-fold, increased odds of long-term treatment. Blacks were less likely than whites to obtain treatment. Utilizers older at follow-up reported longer treatment duration. Mood disorder episodes over follow-up and poorer global functioning were associated with both increased odds of any utilization and increased treatment duration among utilizers. Conclusions: This sample demonstrated high and persistent treatment utilization. Need indicated by childhood diagnosis was the strongest predictor of treatment; however, utilization also differed by race or ethnicity. Strategies to maximize the uptake of effective, culturally relevant treatment approaches should be investigated. C1 Columbia Univ, Dept Psychiat, Div Clin Genet Epidemiol, Coll Phys & Surg, New York, NY USA. New York State Psychiat Inst & Hosp, Div Clin Genet Epidemiol, New York, NY 10032 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, 5635 Fishers Lane,Room 3068,Mail Stop 9304, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU NIMH NIH HHS [R01-MH50666] NR 64 TC 8 Z9 8 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2006 VL 57 IS 7 BP 966 EP 975 DI 10.1176/appi.ps.57.7.966 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 059AX UT WOS:000238706800008 PM 16816281 ER PT J AU Saha, TD Chou, SP Grant, BF AF Saha, Tulshi D. Chou, S. Patricia Grant, Bridget F. TI Toward an alcohol use disorder continuum using item response theory: results from the National Epidemiologic Survey on Alcohol and Related Conditions SO PSYCHOLOGICAL MEDICINE LA English DT Article ID HEALTH INTERVIEW SURVEY; MARGINAL MAXIMUM-LIKELIHOOD; SUBSTANCE USE DISORDERS; LATENT CLASS ANALYSIS; DSM-IV ALCOHOL; AUDADIS-ADR; PARAMETER-ESTIMATION; DEPENDENCE SCALE; SCHEDULE AUDADIS; EM ALGORITHM AB Background. Item response theory (IRT) was used to determine whether the DSM-IV diagnostic criteria for alcohol abuse and dependence are arrayed along a continuum of severity. Method. Data came from a large nationally representative sample of the US population, IS years and older. A two-parameter logistic IRT model was used to determine the severity and discrimination of each DSM-IV criterion. Differential criterion functioning (DCF) was also assessed across subgroups of the Population defined by sex. age and race-ethnicity. Results. All DSM-IV alcohol abuse and dependence criteria. except alcohol-related legal problems. formed a continuum of alcohol use disorder severity. Abuse and dependence criteria did not consistently tap the mildest or more severe end of the continuum respectively. and several criteria were identified as potentially redundant. The drinking, in larger amounts or for longer than intended dependence criterion had the greatest discrimination and lowest severity than any other criterion. Although several criteria were found to function differentially between Subgroups defined in terms of sex and age. there vas evidence that the generalizability and validity of tale criterion forming the continuum remained intact at the test score level. Conclusions. DSM-IV diagnostic criteria for alcohol abuse and dependence form a Continuum Of severity, calling into question the abuse-dependence distinction in the DSM-IV and the Interpretation of abuse as a milder disorder than dependence. The criteria tapped the more severe end of the alcohol use disorder continuum, highlighting the need to identify other criteria capturing the mild to intermediate range of the severity. The drinking larger amounts or longer than intended dependence criterion may be a bridging criterion between drinking patterns that incur risk of alcohol disorder at the milder end of the continuum. With tolerance. withdrawal, impaired control and serious social and Occupational dysfunction at the more severe end of the alcohol use disorder continuum. Future IRT and other dimensional analyses told great promise in informing revisions to categorical classifications and constructing new dimensional classifications of alcohol use disorders based on the DSM and the ICD. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3077,5635 Fishers Lane,MS 9304, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU Intramural NIH HHS NR 58 TC 222 Z9 222 U1 5 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2006 VL 36 IS 7 BP 931 EP 941 DI 10.1017/S003329170600746X PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 061OF UT WOS:000238881300005 PM 16563205 ER PT J AU Blanco, C Hasin, DS Petry, N Stinson, FS Grant, BF AF Blanco, Carlos Hasin, Deborah S. Petry, Nancy Stinson, Frederick S. Grant, Bridget F. TI Sex differences in subclinical and DSM-IV pathological gambling: results from the National Epidemiologic Survey on Alcohol and Related Conditions SO PSYCHOLOGICAL MEDICINE LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; FUNCTIONAL DNA POLYMORPHISM; GENERAL-POPULATION SAMPLE; USE DISORDER CRITERIA; UNITED-STATES; GENDER-DIFFERENCES; DRUG MODULES; PERSONALITY-DISORDERS; PSYCHIATRIC-DISORDERS; PROBLEM GAMBLERS AB Background. To examine sex differences in DSM-IV subclinical and pathological gambling in nationally representative data of the US population. Method. Data come from a large (n = 43 093) representative sample of the adult US population. Results. The lifetime prevalence rate of DSM-IV pathological gambling was 0 center dot 64% (95% CI 0 center dot 50-0 center dot 78) for inert and 0 center dot 23% (95% CI 0 center dot 17-0 center dot 29) for women, whereas the lifetime prevalence of subclinical pathological gambling was 6 center dot 79% (95% CI 6 center dot 32-7 center dot 26) for men and 1 center dot 26% (95% CI 2 center dot 93-3 center dot 59) for women. For subclinical pathological gambling, men were significantly (p < 0 center dot 01) more likely than women to have smoked more than two packs of cigarettes a day. to be classified as heavy drinkers and to have lifetime diagnoses of alcohol and drug use disorders. Women with subclinical and pathological gambling were significantly more likely than men to have lifetime mood and anxiety disorders. With respect to pathological gambling, women had later ages of onset of the disorder. and were significantly more likely than men to report gambling to relieve depressed mood and to prefer casino gambling. Rates of treatment-seeking for DSM-IV pathological gambling were low for both men and women. Conclusions. There are important sex differences in the prevalence. symptom pattern. socio-demographic and clinical correlates and course of DSM-IV subclinical and pathological gambling. Results underscore the need to investigate sex differences in the social determinants. neurobiology and treatment response of DSM-IV subclinical and pathological gambling. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT USA. Columbia Univ, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU Intramural NIH HHS; NIAAA NIH HHS [P50-AA03510, K05-AA014223]; NIDA NIH HHS [K23-DA00482, P50-DA09241, R01-DA016855, R01-DA13444, R01-DA14618, R03-5R03DA15559]; NIMH NIH HHS [R01-MH60417] NR 46 TC 122 Z9 124 U1 2 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2006 VL 36 IS 7 BP 943 EP 953 DI 10.1017/S0033291706007410 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 061OF UT WOS:000238881300006 PM 16650342 ER PT J AU Smith, SM Stinson, FS Dawson, DA Goldstein, R Huang, B Grant, BF AF Smith, Sharon M. Stinson, Frederick S. Dawson, Deborah A. Goldstein, Rise Huang, Boji Grant, Bridget F. TI Race/ethnic differences in the prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions SO PSYCHOLOGICAL MEDICINE LA English DT Article ID COMORBIDITY SURVEY REPLICATION; IV PSYCHIATRIC-DISORDERS; MENTAL-HEALTH RESEARCH; UNITED-STATES; 12-MONTH PREVALENCE; LIFETIME PREVALENCE; RELIABILITY; VALIDITY; DEPENDENCE; DIAGNOSES AB Background. Very few large national epidemiologic surveys have examined the prevalence of psychiatric disorders among Asians and Native Americans due to small sample sizes. Very little is also known about the co-occurrences between substance use disorders and mood and anxiety disorders among these two minority groups and how their rates compare to Whites. Blacks, and Hispanics. Method. Analyses were based on a large (n = 41093) nationally representative survey of the adult (18+ years), U.S. population Supplemented by a group quarters sampling frame. Prevalences and associations of major DSM-IV mood, anxiety an substance use disorders were examined among all major race/ethnic subgroups of the population. Results. Twelve-month rates of most mood, anxiety and substance use disorders were generally greatest among Native Americans and lowest among Asians. For most race/ethnic subgroups, alcohol and drug dependence, but not abuse, were significantly associated with mood disorders. With few exceptions, there were no significant associations between alcohol and drug abuse and anxiety disorders. In contrast. alcohol dependence was associated with most anxiety disorders among Whites, Blacks and Asians. but not among Native Americans. Conclusions. The 12-month prevalence of substance use, mood, and anxiety disorders varied greatly across the five major race/ethnic subgroups of the population. Twelve-month co-occurrence of substance use disorders and mood and anxiety disorders was pervasive among all race/ethnic subgroups. Future research is also needed to understand race/ethnic differentials in prevalence and co-occurrence of these disorders with a particular focus on factors that may Live rise to them. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS NR 41 TC 63 Z9 63 U1 4 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2006 VL 36 IS 7 BP 987 EP 998 DI 10.1017/S0033291706007690 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 061OF UT WOS:000238881300010 PM 16650344 ER PT J AU Markham, JA Beckel-Mitchener, AC Estrada, CM Greenough, WT AF Markham, JA Beckel-Mitchener, AC Estrada, CM Greenough, WT TI Corticosterone response to acute stress in a mouse model of Fragile X syndrome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE glucocorticoid; FMRP; Fmr1; sex difference; acute restraint ID FMR1; MICE; EXPRESSION; DEFICITS; CORTISOL; MEMORY AB Fragile X syndrome (FXS), the most common form of inherited mental retardation, results from the silencing of the Fmr1 gene that encodes the Fragile X mental retardation protein (FMRP). Because (1) mRNA for the glucocorticoid receptor is bound by FMRP and (2) the response to acute stress is elevated in children with FXS, we examined whether this heightened response is characteristic of a mouse model of FXS. Fmr1 knockout (KC) and witdtype (WT) control mice were exposed to 30 min of acute restraint; serum corticosterone levels were assayed from unstressed animals and those examined either immediately following stress or after a 15 or 60 min recovery period. Under unstressed conditions, KOs and WTs did not differ in serum corticosterone, although both genotype and sex affected corticosterone levels observed following exposure to acute stress. Similar to FXS patients, serum glucocorticoid levels of KO mice exhibited a protracted return to baseline following acute stress. This suggests that the stress response is misregulated in Fmr1 KO mice as in FXS patients and provides the first evidence for a link between a particular FMRP-binding mRNA and a functional phenotype of FXS (impaired glucocorticoid negative feedback). (c) 2006 Elsevier Ltd. Alt rights reserved. C1 Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. Univ Illinois, Dept Mol & Cellular Biol, Urbana, IL 61801 USA. Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. NIMH, Mol Cellular & Genom Neurosci Res Branch, Div Neurosci & Basic Behav Sci, Ctr Neurosci, Bethesda, MD 20892 USA. RP Markham, JA (reprint author), Univ Illinois, Beckman Inst, 405 N Mathews Ave, Urbana, IL 61801 USA. EM jmarkham@s.psych.uiuc.edu FU NICHD NIH HHS [HD07333]; NIMH NIH HHS [MH35321] NR 15 TC 35 Z9 35 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JUL PY 2006 VL 31 IS 6 BP 781 EP 785 DI 10.1016/j.psyneuen.2006.02.008 PG 5 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 053BU UT WOS:000238279400010 PM 16621323 ER PT J AU Lubin, JH Wang, ZY Wang, LD Boice, JD Cui, HX Zhang, SR Conrath, S Xia, Y Shang, B Cao, JS Kleinerman, RA AF Lubin, JH Wang, ZY Wang, LD Boice, JD Cui, HX Zhang, SR Conrath, S Xia, Y Shang, B Cao, JS Kleinerman, RA TI Comments on "Adjusting lung cancer risks for temporal and spatial variations in radon concentrations in dwellings in Gansu Province, China" by Lubin et al. (Radiat. Res. 163, 571-579, 2005) - Response SO RADIATION RESEARCH LA English DT Letter ID RESIDENTIAL RADON; EXPOSURE C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Minist Hlth, Lab Ind Hyg, Beijing, Peoples R China. Int Epidemiol Inst, Rockville, MD USA. US EPA, Washington, DC 20460 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. EM lubinj@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 121 EP 121 DI 10.1667/RR3566a.1 PN 1 PG 1 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XA UT WOS:000238627300016 ER PT J AU Simon, SL Kleinerman, RA Ron, E Bouville, A AF Simon, SL Kleinerman, RA Ron, E Bouville, A TI Introduction - Uses of dosimetry in radiation epidemiology SO RADIATION RESEARCH LA English DT Editorial Material ID ATOMIC-BOMB SURVIVORS; CHERNOBYL CLEANUP WORKERS; LUNG-CANCER RISK; RESIDENTIAL RADON; CHROMOSOME-ABERRATIONS; EXPOSURE; CERVIX; FALLOUT; ERRORS; RECONSTRUCTION C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7100, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 39 TC 8 Z9 9 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 125 EP 127 DI 10.1667/RR3385.1 PN 2 PG 3 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500001 PM 16808601 ER PT J AU Brill, AB Stabin, M Bouville, A Ron, E AF Brill, AB Stabin, M Bouville, A Ron, E TI Normal organ radiation dosimetry and associated uncertainties in nuclear medicine, with emphasis on iodine-131 SO RADIATION RESEARCH LA English DT Review ID DIFFERENTIATED THYROID-CARCINOMA; RADIONUCLIDE-S VALUES; PERSONAL-COMPUTER SOFTWARE; INTERNAL DOSE ASSESSMENT; THERAPY FOLLOW-UP; ABSORBED FRACTIONS; RADIOACTIVE IODINE; CANCER-MORTALITY; HYPERTHYROIDISM; RADIOIODINE AB In many medical applications involving the administration of iodine-131 (I-131) in the form of iodide (I-), most of the dose is delivered to the thyroid gland. To reliably estimate the thyroid absorbed dose, the following data are required: the thyroid gland size (i.e. mass), the fractional uptake of I-131 by the thyroid, the spatial distribution of I-131 within the thyroid, and the length of time I-131 is retained in the thyroid before it is released back to blood, distributed in other organs and tissues, and excreted from the body. Estimation of absorbed dose to nonthyroid tissues likewise requires knowledge of the time course of activity in each organ. Such data are rarely available, however, and therefore dose calculations are generally based on reference models. The MIRD and ICRP have published metabolic models and have calculated absorbed doses per unit intake for many nuclides and radioactive pharmaceuticals. Given the activity taken into the body, one can use such models and make reasonable calculations for average organ doses. When normal retention and excretion pathways are altered, the baseline models need to be modified, and the resulting organ dose estimates are subject to larger errors. This paper describes the historical evolution of radioactive isotopes in medical diagnosis and therapy. We nonmathematically summarize the methods used in current practice to estimate absorbed dose and summarize some of the risk data that have emerged from medical studies of patients with special attention to dose and effects observed in those who received I-131-iodide in diagnosis and/or therapy. (c) 2006 by Radiation Research Society. C1 Vanderbilt Univ, Nashville, TN 37232 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Brill, AB (reprint author), Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37232 USA. EM aaron.brill@vanderbilt.edu RI Brill, Aaron/H-3732-2014 OI Brill, Aaron/0000-0001-7538-086X FU Intramural NIH HHS NR 108 TC 14 Z9 14 U1 0 U2 10 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 128 EP 140 DI 10.1667/RR3558.1 PN 2 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500002 PM 16808602 ER PT J AU Stovall, M Weathers, R Kasper, C Smith, SA Travis, L Ron, E Kleinerman, R AF Stovall, M Weathers, R Kasper, C Smith, SA Travis, L Ron, E Kleinerman, R TI Dose reconstruction for therapeutic and diagnostic radiation exposures: Use in epidemiological studies SO RADIATION RESEARCH LA English DT Review ID NASOPHARYNGEAL RADIUM IRRADIATION; NON-HODGKINS-LYMPHOMA; CANCER FOLLOWING RADIOTHERAPY; RISK FOLLOWING RADIOTHERAPY; X-RAY EPILATION; BREAST-CANCER; LUNG-CANCER; CHILDHOOD-CANCER; THYROID-CANCER; TINEA-CAPITIS AB This paper describes methods developed specifically for reconstructing individual organ- and tissue-absorbed dose of radiation from past exposures from medical treatments and procedures for use in epidemiological studies. These methods have evolved over the past three decades and have been applied to a variety of medical exposures including external-beam radiation therapy and brachytherapy for malignant and benign diseases as well as diagnostic examinations. The methods used for estimating absorbed dose to organs in and outside the defined treatment volume generally require archival data collection, abstraction and review, and phantom measurements to simulate past exposure conditions. Three techniques are used to estimate doses from radiation therapy: (1) calculation in three-dimensional mathematical computer models using an extensive database of out-of-beam doses measured in tissue-equivalent materials, (2) measurement in anthropomorphic phantoms constructed of tissue-equivalent material, and (3) calculation using a three-dimensional treatment-planning computer. For diagnostic exposures, doses are estimated from published data and software based on Monte Carlo techniques. We describe and compare these methods of dose estimation and discuss uncertainties in estimated organ doses and potential for future improvement. Seven epidemiological studies are discussed to illustrate the methods. (c) 2006 by Radiation Research Society. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Stovall, M (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Unit 544,1515 Holcombe Blvd, Houston, TX 77030 USA. EM mstovall@mdanderson.org OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP-91024] NR 106 TC 97 Z9 97 U1 3 U2 8 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 141 EP 157 DI 10.1667/RR3525.1 PN 2 PG 17 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500003 PM 16808603 ER PT J AU Bouville, A Chumak, VV Inskip, PD Kryuchkov, V Luckyanov, N AF Bouville, A Chumak, VV Inskip, PD Kryuchkov, V Luckyanov, N TI The Chornobyl accident: Estimation of radiation doses received by the Baltic and Ukrainian cleanup workers SO RADIATION RESEARCH LA English DT Article ID BIODOSIMETRY; DOSIMETRY AB During the first day after the explosion, the Chornobyl accident of April 26, 1986 exposed a few hundred emergency workers to high dose levels ranging up to 16 Gy, resulting in acute radiation syndrome. Subsequently, several hundred thousand cleanup workers were sent to the Chornobyl power plant to mitigate the consequences of the accident. Depending on the nature of the work to be carried out, the cleanup workers were sent for periods ranging from several minutes to several months. The average dose from external radiation exposure that was received by the cleanup workers was about 170 mGy in 1986 and decreased from year to year. The radiation exposure was mainly due to external irradiation from gamma-ray-emitting radionuclides and was relatively homogeneous over all organs and tissues of the body. To assess the possible health consequences of external irradiation at relatively low dose rates, the U.S. National Cancer Institute is involved in two studies of Chornobyl cleanup workers: (1) a study of cancer incidence and thyroid disease among Estonian, Latvian and Lithuanian workers, and (2) a study of leukemia and other related blood diseases among Ukrainian workers. After an overview of the sources of exposure and of the radiation doses received by the cleanup workers, a description of the efforts made to estimate individual doses in the Baltic and Ukrainian studies is presented. (c) 2006 by Radiation Research Society. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA. Ukraine Acad Med Sci, Res Ctr Radiat Med, UA-254050 Kiev, Ukraine. Minist Publ Hlth Russia, State Res Ctr, Inst Biophys, Moscow 123128, Russia. RP Bouville, A (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,DHHS, 6120 Execut Blvd,Room 7094, Bethesda, MD 20892 USA. EM bouvilla@mail.nih.gov RI Chumak, Vadim/N-6960-2015 OI Chumak, Vadim/0000-0001-6045-9356 NR 31 TC 12 Z9 14 U1 1 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 158 EP 167 DI 10.1667/RR3370.1 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500004 PM 16808604 ER PT J AU Gilbert, ES Thierry-Chef, I Cardis, E Fix, JJ Marshall, M AF Gilbert, ES Thierry-Chef, I Cardis, E Fix, JJ Marshall, M TI External dose estimation for nuclear worker studies SO RADIATION RESEARCH LA English DT Article ID RADIATION; MORTALITY; EXPOSURE; ENERGY; BIAS AB Epidemiological studies of nuclear workers are an important source of direct information on the health effects of exposure to radiation at low doses and low dose rates. These studies have the important advantage of doses that have been measured objectively through the use of personal dosimeters. However, to make valid comparisons of worker-based estimates with those obtained from data on A-bomb survivors or persons exposed for medical reasons, attention must be given to potential biases and uncertainties in dose estimates. This paper discusses sources of error in worker dose estimates and describes efforts that have been made to quantify these errors. Of particular importance is the extensive study of errors in dosimetry that was conducted as part of a large collaborative study of nuclear workers in 15 countries being coordinated by the International Agency for Research on Cancer. The study, which focused on workers whose dose was primarily from penetrating gamma radiation in the range 100 keV to 3 MeV, included (1) obtaining information on dosimetry practices and radiation characteristics through the use of questionnaires; (2) two detailed studies of exposure conditions, one of nuclear power plants and the other of mixed activity facilities; and (3) a study of dosimeter response characteristics that included laboratory testing of 10 dosimeter designs commonly used historically. Based on these efforts, facility- and calendar year-specific adjustment factors have been developed, which will allow risks to be expressed as functions of organ doses with reasonable confidence. (c) 2006 by Radiation Research Society. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Pacific NW Natl Lab, Richland, WA USA. Twin Trees, Blewbury, Oxon, England. RP Gilbert, ES (reprint author), Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, 6120 Execut Blvd,Room 7050, Rockville, MD 20852 USA. EM gilberte@mail.nih.gov RI Cardis, Elisabeth/C-3904-2017 NR 22 TC 7 Z9 7 U1 0 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 168 EP 173 DI 10.1667/RR3126.1 PN 2 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500005 PM 16808605 ER PT J AU Simon, SL Weinstock, RM Doody, MM Neton, J Wenzl, T Stewart, P Mohan, AK Yoder, RC Hauptmann, M Freedman, DM Cardarelli, J Feng, HA Bouville, A Linet, M AF Simon, SL Weinstock, RM Doody, MM Neton, J Wenzl, T Stewart, P Mohan, AK Yoder, RC Hauptmann, M Freedman, DM Cardarelli, J Feng, HA Bouville, A Linet, M TI Estimating historical radiation doses to a cohort of US Radiologic Technologists SO RADIATION RESEARCH LA English DT Article ID X-RAY WORKERS; CANCER INCIDENCE; OCCUPATIONAL-EXPOSURE; MORTALITY; CHINA; PROTECTION; HEALTH; STAFF; RISK; ARMY AB Data have been collected and physical and statistical models have been constructed to estimate unknown occupational radiation doses among 90,000 members of the U.S. Radiologic Technologists cohort who responded to a baseline questionnaire during the mid-1980s. Since the availability of radiation dose data differed by calendar period, different models were developed and applied for years worked before 1960, 1960-1976 and 1977-1984. The dose estimation used available film-badge measurements (approximately 350,000) for individual cohort members, information provided by the technologists on their work history and protection practices, and measurement and other data derived from the literature. The dosimetry model estimates annual and cumulative occupational badge doses (personal dose equivalent) for each technologist for each year worked from 1916 through 1984 as well as absorbed doses to organs and tissues including bone marrow, female breast, thyroid, ovary, testes, lung and skin. Assumptions have been made about critical variables including average energy of X rays, use of protective aprons, position of film badges, and minimum detectable doses. Uncertainty of badge and organ doses was characterized for each year of each technologist's working career. Monte Carlo methods were used to generate estimates of cumulative organ doses for preliminary cancer risk analyses. The models and predictions presented here, while continuing to be modified and improved, represent one of the most comprehensive dose reconstructions undertaken to date for a large cohort of medical radiation workers. (c) 2006 by Radiation Research Society. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NIOSH, Cincinnati, OH 45226 USA. RTI Int, Bethesda, MD USA. Johnson & Johnson PRD, Titusville, NJ USA. Landauer Inc, Glenwood, IL USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7100, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 52 TC 37 Z9 37 U1 1 U2 7 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 174 EP 192 DI 10.1667/RR3433.1 PN 2 PG 19 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500006 PM 16808606 ER PT J AU Beck, HL Anspaugh, LR Bouville, A Simon, SL AF Beck, Harold L. Anspaugh, Lynn R. Bouville, Andre Simon, Steven L. TI Review of methods of dose estimation for epidemiological studies of the radiological impact of Nevada test site and global fallout SO RADIATION RESEARCH LA English DT Review ID CONTINENTAL UNITED-STATES; MARSHALL-ISLANDS; THYROID-DISEASE; NUCLEAR TESTS; INGESTION; UTAH; RADIONUCLIDES; POPULATIONS; RADIOIODINE; LEUKEMIA AB Methods to assess radiation doses from nuclear weapons test fallout have been used to estimate doses to populations and individuals in a number of studies. However, only a few epidemiology studies have relied on fallout dose estimates. Though the methods for assessing doses from local and regional compared to global fallout are similar, there are significant differences in predicted doses and contributing radionuclides depending on the source of the fallout, e.g. whether the nuclear debris originated in Nevada at the U.S. nuclear test site or whether it originated at other locations worldwide. The sparse historical measurement data available are generally sufficient to estimate external exposure doses reasonably well. However, reconstruction of doses to body organs from ingestion and inhalation of radionuclides is significantly more complex and is almost always more uncertain than are external dose estimates. Internal dose estimates are generally based on estimates of the ground deposition per unit area of specific radionuclides and subsequent transport of radionuclides through the food chain. A number of technical challenges to correctly modeling deposition of fallout under wet and dry atmospheric conditions still remain, particularly at close-in locations where sizes of deposited particles vary significantly over modest changes in distance. This paper summarizes the various methods of dose estimation from weapons test fallout and the most important dose assessment and epidemiology studies that have relied on those methods. (c) 2006 by Radiation Research Society. C1 Univ Utah, Div Radiobiol, Salt Lake City, UT 84112 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Beck, HL (reprint author), 33 Greenwich Ave,11-G, New York, NY USA. EM hbeck@worldnet.att.net NR 58 TC 7 Z9 7 U1 3 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 209 EP 218 DI 10.1667/RR3172.1 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500008 PM 16808609 ER PT J AU Likhtarev, I Bouville, A Kovgan, L Luckyanov, N Voilleque, P Chepurny, M AF Likhtarev, I. Bouville, A. Kovgan, L. Luckyanov, N. Voilleque, P. Chepurny, M. TI Questionnaire- and measurement-based individual thyroid doses in Ukraine resulting from the Chornobyl nuclear reactor accident SO RADIATION RESEARCH LA English DT Article ID SHORT-LIVED RADIOIODINES; COW-MILK PATHWAY; CANCER; BYELARUS; CHILDREN; RECONSTRUCTION; RADIATION; FALLOUT; IODINE; I-131 AB The U.S. National Cancer Institute (NCI), in cooperation with the Ministries of Health of Belarus and of Ukraine, is involved in epidemiological studies of thyroid diseases presumably related to the Chornobyl accident, which occurred in Ukraine on 26 April 1986. Within the framework of these studies, individual thyroid absorbed doses, as well as uncertainties, have been estimated for all members of the cohorts (13,215 Ukrainians and 11,918 Belarusians), who were selected from the large group of children aged 0 to 18 whose thyroids were monitored for gamma radiation within a few weeks after the accident. Information on the residence history and dietary habits of each cohort member was obtained during personal interviews. The methodology used to estimate the thyroid absorbed doses resulting from intakes of (131)I by the Ukrainian cohort subjects is described. The model of thyroid dose estimation is run in two modes: deterministic and stochastic. In the stochastic mode, the model is run 1,000 times for each subject using a Monte Carlo procedure. The geometric means of the individual thyroid absorbed doses obtained in the stochastic mode range from 0.0006 to 42 Gy. The arithmetic and geometric means of these individual thyroid absorbed doses over the entire cohort are 0.68 and 0.23 Gy, respectively. On average, the individual thyroid dose estimates obtained in the deterministic mode are about the same as the geometric mean doses obtained in the stochastic mode, while the arithmetic mean thyroid absorbed doses obtained in the stochastic mode are about 20% higher than those obtained in the deterministic mode. The distributions of the 1000 values of the individual thyroid absorbed dose estimates are found to be approximately lognormal, with geometric standard deviations ranging from 1.6 to 5.0 for most cohort subjects. For the time being, only the thyroid doses resulting from intakes of (131)I have been estimated for all subjects. Future work will include the estimation of the contributions to the thyroid doses resulting from external irradiation and from intakes of short-lived ((133)I and (132)Te) and long-lived ((134)Cs and (137)Cs) radionuclides, as well as efforts to reduce the uncertainties. (c) 2006 by Radiation Research Society. C1 Natl Canc Inst, DHHS, NIH,CRU, Div Canc Epidemiol & Genet,REB, Bethesda, MD 20892 USA. Ukrainian Acad Technol Sci, Radiat Protect Inst, UA-04050 Kiev, Ukraine. MJP Risk Assessment Inc, Denver, CO 80230 USA. RP Bouville, A (reprint author), Natl Canc Inst, DHHS, NIH,CRU, Div Canc Epidemiol & Genet,REB, 6120 Execut Blvd,EPS 7094, Bethesda, MD 20892 USA. EM bouvilla@mail.nih.gov NR 36 TC 34 Z9 34 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 271 EP 286 DI 10.1667/RR3545.1 PN 2 PG 16 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500011 PM 16808613 ER PT J AU Kleinerman, RA Romanyukha, AA Schauer, DA Tucker, JD AF Kleinerman, RA Romanyukha, AA Schauer, DA Tucker, JD TI Retrospective assessment of radiation exposure using biological dosimetry: Chromosome painting, electron paramagnetic resonance and the glycophorin A mutation assay SO RADIATION RESEARCH LA English DT Review ID CHERNOBYL CLEANUP WORKERS; IN-SITU HYBRIDIZATION; EPR DOSE RECONSTRUCTION; ATOMIC-BOMB SURVIVORS; NUCLEAR TEST-SITE; SOMATIC-CELL MUTATIONS; DNA-REPAIR CAPACITY; TOOTH ENAMEL; IONIZING-RADIATION; MUTAGEN SENSITIVITY AB Biological monitoring of dose can contribute important, independent estimates of cumulative radiation exposure in epidemiological studies, especially in studies in which the physical dosimetry is lacking. Three biodosimeters that have been used in epidemiological studies to estimate past radiation exposure from external sources will be highlighted: chromosome painting or FISH (fluorescence in situ hybridization), the glycophorin A somatic mutation assay (GPA), and electron paramagnetic resonance (EPR) with teeth. All three biodosimeters have been applied to A-bomb survivors, Chernobyl clean-up workers, and radiation workers. Each biodosimeter has unique advantages and limitations depending upon the level and type of radiation exposure. Chromosome painting has been the most widely applied biodosimeter in epidemiological studies of past radiation exposure, and results of these studies provide evidence that dose-related translocations persist for decades. EPR tooth dosimetry has been used to validate dose models of acute and chronic radiation exposure, although the present requirement of extracted teeth has been a disadvantage. GPA has been correlated with physically based radiation dose after high-dose, acute exposures but not after low-dose, chronic exposures. Interindividual variability appears to be a limitation for both chromosome painting and GPA. Both of these techniques can be used to estimate the level of past radiation exposure to a population, whereas EPR can provide individual dose estimates of past exposure. This paper will review each of these three biodosimeters and compare their application in selected epidemiological studies. (c) 2006 by Radiation Research Society. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. Natl Council Radiat Protect & Measurements, Bethesda, MD 20814 USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. EM kleinerr@exchange.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 NR 120 TC 29 Z9 31 U1 2 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 287 EP 302 DI 10.1667/RR3273.1 PN 2 PG 16 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500012 PM 16808614 ER PT J AU Schafer, DW Gilbert, ES AF Schafer, DW Gilbert, ES TI Some statistical implications of dose uncertainty in radiation dose-response analyses SO RADIATION RESEARCH LA English DT Article ID COVARIATE MEASUREMENT ERRORS; EXPOSURE MEASUREMENT ERROR; BOMB SURVIVOR DATA; LUNG-CANCER; RESIDENTIAL RADON; RISK; DISEASE; REANALYSIS; MORTALITY; VARIABLES AB Statistical dose-response analyses in radiation epidemiology can produce misleading results if they fail to account for radiation dose uncertainties. While dosimetries may differ substantially depending on the ways in which the subjects were exposed, the statistical problems typically involve a predominantly linear dose-response curve, multiple sources of uncertainty, and uncertainty magnitudes that are best characterized as proportional rather than additive. We discuss some basic statistical issues in this setting, including the bias and shape distortion induced by classical and Berkson uncertainties, the effect of uncertain dose-prediction model parameters on estimated dose-response curves, and some notes on statistical methods for dose-response estimation in the presence of radiation dose uncertainties. (c) 2006 by Radiation Research Society. C1 Oregon State Univ, Dept Stat, Corvallis, OR 97331 USA. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Schafer, DW (reprint author), Oregon State Univ, Dept Stat, 44 Kidder Hall, Corvallis, OR 97331 USA. EM schafer@science.oregonstate.edu NR 34 TC 35 Z9 37 U1 0 U2 6 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 303 EP 312 DI 10.1667/RR3358.1 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500013 PM 16808615 ER PT J AU Simon, SL Bouville, A Kleinerman, R Ron, E AF Simon, SL Bouville, A Kleinerman, R Ron, E TI Summary - Dosimetry for epidemiological studies: Learning from the past, looking to the future SO RADIATION RESEARCH LA English DT Editorial Material ID ICRPS DOSE COEFFICIENTS; RADIONUCLIDES; UNCERTAINTIES; RELIABILITY; MEMBERS C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7100, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 25 TC 9 Z9 9 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 313 EP 318 DI 10.1667/RR3536.1 PN 2 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XC UT WOS:000238627500014 PM 16808617 ER PT J AU Bagley, DM Casterton, PL Dressler, WE Edelhauser, HF Kruszewski, FH McCulley, JP Nussenblatt, RB Osborne, R Rothenstein, A Stitzel, KA Thomas, K Ward, SL AF Bagley, Daniel M. Casterton, Phillip L. Dressler, William E. Edelhauser, Henry F. Kruszewski, Francis H. McCulley, James P. Nussenblatt, Robert B. Osborne, Rosemarie Rothenstein, Arthur Stitzel, Katherine A. Thomas, Karluss Ward, Sherry L. TI Proposed new classification scheme for chemical injury to the human eye SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE chemical eye injury; ocular classification scheme; eye injury classification scheme; alternatives to animals; draize test; draize alternative method ID CORNEAL INJURY; IRRITATION; EXTENT AB Purpose: Various ocular alkali burn classification schemes have been published and used to grade human chemical eye injuries for the purpose of identifying treatments and forecasting outcomes. The ILSI chemical eye injury classification scheme was developed for the additional purpose of collecting detailed human eye injury data to provide information on the mechanisms associated with chemical eye injuries. This information will have clinical application, as well as use in the development and validation of new methods to assess ocular toxicity. Methods: A panel of ophthalmic researchers proposed the new classification scheme based upon current knowledge of the mechanisms of eye injury, and their collective clinical and research experience. Additional ophthalmologists and researchers were surveyed to critique the scheme. The draft scheme was revised, and the proposed scheme represents the best consensus from at least 23 physicians and scientists. Results: The new scheme classifies chemical eye injury into five categories based on clinical signs, symptoms, and expected outcomes. Diagnostic classification is based primarily on two clinical endpoints: (1) the extent (area) of injury at the limbus, and (2) the degree of injury (area and depth) to the cornea. Conclusions: The new classification scheme provides a uniform system for scoring eye injury across chemical classes, and provides enough detail for the clinician to collect data that will be relevant to identifying the mechanisms of ocular injury. (c) 2006 Elsevier Inc. All rights reserved. C1 Colgate Palmolive Co, Piscataway, NJ USA. Alticor Corp, Access Business Grp, MI Burdock Grp, Vero Beach, FL USA. Bristol Myers Squibb Worldwide Beauty Care, Stamford, CT USA. Emory Univ, Atlanta, GA 30322 USA. Soap & Detergent Assoc, Washington, DC USA. Gillette Co, Gaithersburg, MD USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. NIH, Bethesda, MD 20892 USA. Procter & Gamble Co, Cincinnati, OH USA. Unilever, Edgewater, NJ USA. HESI, ILSI, Washington, DC USA. RP Ward, SL (reprint author), BioTred Solut, POB 630, New Market, MD 21774 USA. EM biotred@hotmail.com OI Ward, Sherry/0000-0001-6535-9477 NR 22 TC 9 Z9 11 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2006 VL 45 IS 2 BP 206 EP 213 DI 10.1016/j.yrtph.2006.04.005 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 062PM UT WOS:000238957000009 PM 16764976 ER PT J AU Rogers, NT Halet, G Piao, Y Carroll, J Ko, MSH Swann, K AF Rogers, N. T. Halet, G. Piao, Y. Carroll, J. Ko, M. S. H. Swann, K. TI The absence of a Ca(2+) signal during mouse egg activation can affect parthenogenetic preimplantation development, gene expression patterns, and blastocyst quality SO REPRODUCTION LA English DT Article ID DEPENDENT PROTEIN-KINASE; CALCIUM SIGNAL; METAPHASE ARREST; MICROARRAY DATA; RABBIT OOCYTES; CELL-DEATH; EMBRYO; OSCILLATIONS; APOPTOSIS; FERTILIZATION AB A series of Ca(2+) oscillations during mammalian fertilization is necessary and sufficient to stimulate meiotic resumption and pronuclear formation. it is not known how effectively development continues in the absence of the initial Ca(2+) signal. We have triggered parthenogenetic egg activation with cycloheximide that causes no Ca(2+) increase, with ethanol that causes a single large Ca(2+) increase, or with Sr(2+) that causes Ca(2+) oscillations. Eggs were co-treated with cytochalasin D to make them diploid and they formed pronuclei and two-cell embryos at high rates with each activation treatment. However, far fewer of the embryos that were activated by cycloheximide reached the blastocyst-stage compared to those activated by Sr(2+) orethanol. Any cycloheximide-activated embryos that reached the blastocyst stage had a smaller inner cell mass number and a greater rate of apoptosis than Sr(2+)-activated embryos. The poor development of cycloheximide-activated embryos was due to the lack of Ca(2+) increase because they developed to blastocyst stages at high rates when co-treated with Sr(2+) or ethanol. Embryos activated by either Sr 21 or cycloheximide showed similar signs of initial embryonic genome activation (EGA) when measured using a reporter gene. However, microarray analysis of gene expression at the eight-cell stage showed that activation by Sr(2+) leads to a distinct pattern of gene expression from that seen with embryos activated by cycloheximide. These data suggest that activation of mouse eggs in the absence of a Ca(2+) signal does not affect initial parthenogenetic events, but can influence later gene expression and development. C1 UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. UCL, Dept Physiol, London WC1E 6BT, England. NIA, Lab Genet, Dev Genom & Aging Sect, NIH, Baltimore, MD 21224 USA. Cardiff Univ, Sch Med, Dept Obstet & Gynaecol, Cardiff CF14 4XN, Wales. RP Swann, K (reprint author), UCL, Dept Anat & Dev Biol, Gower St, London WC1E 6BT, England. EM swannk1@cf.ac.uk RI Ko, Minoru/B-7969-2009; halet, guillaume/C-7502-2009; OI Ko, Minoru/0000-0002-3530-3015; Halet, Guillaume/0000-0002-6204-2105 FU Intramural NIH HHS; Medical Research Council [G0400530]; Wellcome Trust NR 52 TC 40 Z9 41 U1 0 U2 4 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD JUL PY 2006 VL 132 IS 1 BP 45 EP 57 DI 10.1530/rep.1.01059 PG 13 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 069DA UT WOS:000239424600005 PM 16816332 ER PT J AU Smirnova, NA Romanienko, PJ Khil, PP Camerini-Otero, RD AF Smirnova, Natalya A. Romanienko, Peter J. Khil, Pavel P. Camerini-Otero, R. Daniel TI Gene expression profiles of Spo11(-/-) mouse testes with spermatocytes arrested in meiotic prophase I SO REPRODUCTION LA English DT Article ID DOUBLE-STRAND BREAKS; HOMOLOGOUS CHROMOSOME SYNAPSIS; SPERMATOGENIC CELLS; HOP2 PROTEIN; GERM-CELLS; MEIOSIS; MICE; RECOMBINATION; PROGRESSION; COMPLEX AB Spo11, a meiosis-specific protein, introduces double-strand breaks on chromosomal DNA and initiates meiotic recombination in a wide variety of organisms. Mouse null Spo11 spermatocytes fail to synapse chromosomes and progress beyond the zygotene stage of meiosis. We analyzed gene expression profiles in Spo11(-/-) adult and juvenile wild-type testis to describe genes expressed before and after the meiotic arrest resulting from the knocking out of Spo11. These genes were characterized using the Gene Ontology data base. To focus on genes involved in meiosis, we performed comparative gene expression analysis of Spo11(-/-) and wild-type testes from 15-day mice, when spermatocytes have just entered pachytene. We found that the knockout of Spo(11) causes dramatic changes in the level of expression of genes that participate in meiotic recombination (Hop2, Brca2, Mnd1, FancG) and in the meiotic checkpoint (cyclin 132, Cks2), but does not affect genes encoding protein components of the synaptonemal complex. Finally, we discovered unknown genes that are affected by the disruption of the Spo11 gene and therefore may be specifically involved in meiosis and spermatogenesis. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, 5 Mem Dr, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov NR 57 TC 14 Z9 15 U1 0 U2 4 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD JUL PY 2006 VL 132 IS 1 BP 67 EP 77 DI 10.1530/rep.1.00997 PG 11 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 069DA UT WOS:000239424600007 PM 16816334 ER PT J AU Sejvar, JJ Marfin, AA AF Sejvar, James J. Marfin, Anthony A. TI Manifestations of West Nile neuroinvasive disease SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID NEW-YORK-CITY; POLIOMYELITIS-LIKE SYNDROME; NORTHEASTERN UNITED-STATES; VIRUS-INFECTION; CEREBROSPINAL-FLUID; FLACCID PARALYSIS; TRANSPLANT RECIPIENTS; JAPANESE ENCEPHALITIS; SPINAL-CORD; EPIDEMIC AB Since its introduction to North America in 1999, West Nile virus, an arthropod-bome flavivirus, has become the most significant cause of epidemic encephalitis in the western hemisphere. While most human infections with the virus are asymptomatic and the majority of symptomatic persons experience febrile illness, severe neurologic manifestations, including meningitis, encephalitis, and poliomyelitis may be seen. This review summarizes the virology, epidemiology and pathogenesis of human infection with West Nile virus, and details recent advances in our understanding of the pathophysiology and various clinical manifestations of infection. Published in 2006 by John Wiley & Sons, Ltd. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Vector Borne Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. CDC, Div Global Migrat & Quarantine, NCI, San Francisco, CA USA. RP Sejvar, JJ (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Vector Borne Infect Dis, 1600 Clifton Rd,MSA-39, Atlanta, GA 30333 USA. EM zea3@cdc.gov NR 121 TC 38 Z9 44 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD JUL-AUG PY 2006 VL 16 IS 4 BP 209 EP 224 DI 10.1002/rmv.501 PG 16 WC Virology SC Virology GA 070LL UT WOS:000239523800002 PM 16906589 ER PT J AU Bubunenko, M Korepanov, A Court, DL Jagannathan, I Dickinson, D Chaudhuri, BR Garber, MB Culver, GM AF Bubunenko, M Korepanov, A Court, DL Jagannathan, I Dickinson, D Chaudhuri, BR Garber, MB Culver, GM TI 30S ribosomal subunits can be assembled in vivo without primary binding ribosomal protein S15 SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE ribosomal proteins; 30S subunit assembly; S15 ID COLD-SENSITIVE MUTATION; ESCHERICHIA-COLI; CENTRAL DOMAIN; THERMUS-THERMOPHILUS; MOLECULAR COMPONENTS; GEL-ELECTROPHORESIS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; RNA; RECONSTITUTION AB Assembly of 30S ribosomal subunits from Escherichia coli has been dissected in detail using an in vitro system. Such studies have allowed characterization of the role for ribosomal protein S15 in the hierarchical assembly of 30S subunits; S15 is a primary binding protein that orchestrates the assembly of ribosomal proteins S6, S11, S18, and S21 with the central domain of 16S ribosomal RNA to form the platform of the 30S subunit. In vitro S15 is the sole primary binding protein in this cascade, performing a critical role during assembly of these four proteins. To investigate the role of S15 in vivo, the essential nature of rpsO, the gene encoding S15, was examined. Surprisingly, E. coli with an in-frame deletion of rpsO are viable, although at 37 degrees C this Delta rpsO strain has an exaggerated doubling time compared to its parental strain. In the absence of S15, the remaining four platform proteins are assembled into ribosomes in vivo, and the overall architecture of the 30S subunits formed in the DrpsO strain at 37 degrees C is not altered. Nonetheless, 30S subunits lacking S15 appear to be somewhat defective in subunit association in vivo and in vitro. In addition, this strain is cold sensitive, displaying a marked ribosome biogenesis defect at low temperature, suggesting that under nonideal conditions S15 is critical for assembly. The viability of this strain indicates that in vivo functional populations of 70S ribosomes must form in the absence of S15 and that 30S subunit assembly has a plasicity that has not previously been revealed or characterized. C1 Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Mol Control & Genet Sect, Gene regulat & Chromosome Biol Lab, Canc Res Ctr, Frederick, MD 21702 USA. Russian Acad Sci, Inst Prot Res, Pushchino 142290, Moscow Region, Russia. RP Culver, GM (reprint author), Iowa State Univ, Dept Biochem Biophys & Mol Biol, 4216 Mol Biol Bldg, Ames, IA 50011 USA. EM gculver@iastate.edu RI Korepanov, Alexey/I-9052-2012; Garber, Maria/I-4262-2013 OI Garber, Maria/0000-0002-3986-4848 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [GM62432, R01 GM062432] NR 36 TC 27 Z9 28 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JUL PY 2006 VL 12 IS 7 BP 1229 EP 1239 DI 10.1261/rna.2262106 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 058NE UT WOS:000238670900010 PM 16682557 ER PT J AU Makhnovskii, YA Berezhkovskii, AM Zitserman, VY AF Makhnovskii, Yu. A. Berezhkovskii, A. M. Zitserman, V. Yu. TI The trapping of diffusing particles by absorbing surface centers SO RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID LIGAND-BINDING; RECEPTORS; HOMOGENIZATION AB The problem of the trapping of diffusing particles by nonoverlapping absorbing patches randomly distributed over a reflecting surface is considered. The suggested approach to its solution is based on the replacement of the inhomogeneous boundary condition on the surface by a radiation boundary condition with an effective rate of trapping the same at all surface points. An equation for the effective rate of the trapping of particles was obtained for absorbing round disks equal in size as reaction patches. The equation, which also described cooperative effects, was generalized to absorbing patches of different sizes and shapes. The possibility of finite absorption by reaction patches was included. The results obtained were in close agreement with computer simulation data obtained by the Brownian dynamics method. C1 Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 117912, Russia. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Russian Acad Sci, Inst High Temp, Sci Assoc, IVTAN, Moscow 127412, Russia. RP Makhnovskii, YA (reprint author), Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Leninskii Pr 29, Moscow 117912, Russia. EM vz1941@mail.ru RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X NR 22 TC 2 Z9 2 U1 0 U2 0 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0036-0244 J9 RUSS J PHYS CHEM+ JI Russ. J. Phys. Chem. PD JUL PY 2006 VL 80 IS 7 BP 1129 EP 1134 DI 10.1134/S0036024406070223 PG 6 WC Chemistry, Physical SC Chemistry GA 156RI UT WOS:000245666400022 ER PT J AU Bagby, GC Alter, BP AF Bagby, Grover C. Alter, Blanche P. TI Fanconi anemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID COMPLEMENTATION-GROUP-C; HEMATOPOIETIC-CELLS; GENE-PRODUCT; MITOMYCIN-C; INTERFERON-GAMMA; DNA-DAMAGE; NUCLEAR-COMPLEX; FANCC(-/-) MICE; STEM-CELLS; BRCA2 C1 OHSU, Inst Canc, Dept Med, Portland, OR 97239 USA. OHSU, Inst Canc, Dept Mol & Med Genet, Portland, OR 97239 USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bagby, GC (reprint author), OHSU, Inst Canc, Dept Med, CR145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM grover@ohsu.edu OI Bagby, Grover/0000-0001-6830-2046 FU Intramural NIH HHS NR 86 TC 95 Z9 100 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2006 VL 43 IS 3 BP 147 EP 156 DI 10.1053/j.seminhematol.2006.04.005 PG 10 WC Hematology SC Hematology GA 063BZ UT WOS:000238992300002 PM 16822457 ER PT J AU Louis, GMB Lynch, CD Cooney, MA AF Louis, Germaine M. Buck Lynch, Courtney D. Cooney, Maureen A. TI Environmental influences on female fecundity and fertility SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE endocrine disruptors; fecundity; fertility; reproduction; toxicity ID PERSISTENT ORGANOCHLORINE COMPOUNDS; MENSTRUAL-CYCLE CHARACTERISTICS; SERUM DIOXIN CONCENTRATIONS; CONTAMINATED SPORT FISH; POLYCHLORINATED-BIPHENYLS; CHILDRENS HEALTH; CHLORINATED HYDROCARBONS; SPONTANEOUS-ABORTION; PESTICIDE EXPOSURE; AROCLOR 1254 AB An increasing body of evidence suggests that environmental exposures are adversely influencing female fecundity and fertility. Endocrine-disrupting compounds (EDCs) are of particular concern, due to their ability to interfere with the body's hormonal milieu. An overview of the literature regarding the effect of EDCs on female fecundity and fertility end points such as puberty, menstruation, endometriosis, time to pregnancy, pregnancy loss, reproductive senescence, and secondary sex ratio is presented. Methodologic challenges in studying the effects EDCs on sensitive reproductive end points are discussed and include exposure to mixtures, the choice of biologic media in which to measure compounds, laboratory methods, and varying modeling techniques. Also reviewed are novel technologies for home-based biospecimen collection and testing that offer promise for field-based research aimed at addressing questions about environmental influences on female fecundity and fertility. C1 Natl Inst Child Hlth & Human Dev, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Louis, GMB (reprint author), Natl Inst Child Hlth & Human Dev, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 NR 68 TC 29 Z9 30 U1 1 U2 11 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JUL PY 2006 VL 24 IS 3 BP 147 EP 155 DI 10.1055/s-2006-944421 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 059JU UT WOS:000238729900004 ER PT J AU Heindel, JJ AF Heindel, JJ TI Role of exposure to environmental chemicals in the developmental basis of reproductive disease and dysfunction SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE development; environmental exposures; reproduction; transgenerational effects; epigenetics ID BISPHENOL-A ALTERS; IN-UTERO EXPOSURE; ENDOCRINE DISRUPTORS; PRENATAL EXPOSURE; DNA METHYLATION; FETAL EXPOSURE; FEMALE MOUSE; MALE-RAT; MICE; DIETHYLSTILBESTROL AB There is a paradigm shift in science at present that indicates that the onset of many diseases, including reproductive diseases and dysfunctions, are already programmed in utero or in the early postnatal period. This new field is called the developmental basis of health and disease. Although focus has been on the role of in utero nutrition and its effects on subsequent adult-onset diseases, it is clear that exposure to environmental stressors/toxicants in utero or during early development can also increase susceptibility to disease later in life. The mechanism for this in utero and early developmental effect is thought to be altered epigenetic control of gene expression, which alters developmental programming and results in a tissue that may appear normal but is functionally compromised. Although this concept is still a hypothesis, this review addresses the current state of data relating to proving its importance and role in reproductive diseases. If the developmental basis of disease is shown to be true, then examination of the etiology of disease and prevention and intervention strategies will need to be modified to fit the new paradigm. C1 Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Cellular Organs & Syst Pathobiol Branch, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Heindel, JJ (reprint author), Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Cellular Organs & Syst Pathobiol Branch, Dept Hlth & Human Serv, 79 TW Alexander Dr,Bldg 4401,3rd Floor,Mail Drop, Res Triangle Pk, NC 27709 USA. EM heindelj@niehs.nih.gov NR 65 TC 35 Z9 37 U1 0 U2 8 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JUL PY 2006 VL 24 IS 3 BP 168 EP 177 DI 10.1055/s-2006-944423 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 059JU UT WOS:000238729900006 PM 16804815 ER PT J AU Song, L Webb, NE Song, YJ Tuan, RS AF Song, Lin Webb, Nicole E. Song, Yingjie Tuan, Rocky S. TI Identification and functional analysis of candidate genes regulating mesenchymal stem cell self-renewal and multipotency SO STEM CELLS LA English DT Article DE mesenchymal stem cells; transdifferentiation; self-renewal; microarray ID HUMAN BONE-MARROW; UMBILICAL-CORD BLOOD; MOLECULAR SIGNATURE; IN-VITRO; MICROARRAY ANALYSIS; PROGENITOR CELLS; CDNA MICROARRAY; DNA MICROARRAY; DIFFERENTIATION; EXPRESSION AB Adult human mesenchymal stem cells (hMSCs) possess multilineage differentiation potential, and differentiated hMSCs have recently been shown to have the ability to transdifferentiate into other lineages. However, the molecular signature of hMSCs is not well-known, and the mechanisms regulating their self-renewal, differentiation, and transdifferentiation are not completely understood. In this study, we demonstrate that fully differentiated hMSCs could dedifferentiate, a likely critical step for transdifferentiation. By comparing the global gene expression profiles of undifferentiated, differentiated, and dedifferentiation cells in three mesenchymal lineages (osteogenesis, chondrogenesis, and adipogenesis), we identified a number of "stemness" and "differentiation" genes that might be essential to maintain adult stem cell multipotency as well as to drive lineage-specific commitment. These genes include those that encode cell surface molecules, as well as components of signaling pathways. These genes may be valuable for developing methods to isolate, enrich, and purify homogeneous population of hMSCs and/or maintain and propagate hMSCs as well as guide or regulate their differentiation for gene and cell-based therapy. Using small interfering RNA gene inactivation, we demonstrate that five genes (actin filament-associated protein, frizzled 7, dickkopf 3, protein tyrosine phosphatase receptor F, and RAB3B) promote cell survival without altering cell proliferation, as well as exhibiting different effects on the commitment of hMSCs into multiple mesenchymal lineages. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 S Dr,Room 1503,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [Z01 AR41113] NR 57 TC 124 Z9 131 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JUL PY 2006 VL 24 IS 7 BP 1707 EP 1718 DI 10.1634/stemcells.2005-0604 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085YE UT WOS:000240639500009 PM 16574750 ER PT J AU Ta, M Choi, Y Atouf, F Park, CH Lumelsky, N AF Ta, Malancha Choi, Yong Atouf, Fouad Park, Cheol Hong Lumelsky, Nadya TI The defined combination of growth factors controls generation of long-term-replicating islet progenitor-like cells from cultures of adult mouse pancreas SO STEM CELLS LA English DT Article DE adult stem cells; bone morphogenetic protem-4; progenitors diabetes; pancreatic islets; proliferation differentiation ID CNS STEM-CELLS; ENDOTHELIAL-CELLS; BETA-CELLS; ENDOCRINE DEVELOPMENT; IN-VIVO; DIFFERENTIATION; EXPRESSION; NESTIN; NOTCH; TRANSCRIPTION AB Application of pancreatic islet transplantation to treatment of diabetes is severely hampered by the inadequate islet supply. This problem could in principle be overcome by generating islet cells from adult pancreas in vitro. Although it is possible to obtain replicating cells from cultures of adult pancreas, these cells, when significantly expanded in vitro, progressively lose pancreatic-specific gene expression, including that of a "master" homeobox transcription factor Pdx1. Here we show for the first time that long-term proliferating islet progenitor-like cells (IPLCs) stably expressing high levels of Pdx1 and other genes that control early pancreatic development can be derived from cultures of adult mouse pancreas under serum-free defined culture conditions. Moreover, we show that cells derived thus can be maintained in continuous culture for at least 6 months without any substantial loss of early pancreatic phenotype. Upon growth factor withdrawal, the IPLCs organize into cell clusters and undergo endocrine differentiation of various degrees in a line-dependent manner. We propose that our experimental strategy will provide a framework for developing efficient approaches for ex vivo expansion of islet cell mass. C1 NIDDK, Islet & Autoimmun Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lumelsky, N (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 45 Ctr Dr,Bldg 45,Room 4N 24J, Bethesda, MD 20892 USA. EM nadyal@nidcr.nih.gov FU Intramural NIH HHS NR 44 TC 14 Z9 21 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 2006 VL 24 IS 7 BP 1738 EP 1749 DI 10.1634/stemcells.2005-0367 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085YE UT WOS:000240639500012 PM 16556710 ER PT J AU Ziolkowska, NE O'Keefe, BR Mori, T Zhu, C Giomarelli, B Vojdani, F Palmer, KE McMahon, JB Wlodawer, A AF Ziolkowska, Natasza E. O'Keefe, Barry R. Mori, Toshiyuki Zhu, Charles Giomarelli, Barbara Vojdani, Fakhrieh Palmer, Kenneth E. McMahon, James B. Wlodawer, Alexander TI Domain-swapped structure of the potent antiviral protein griffithsin and its mode of carbohydrate binding SO STRUCTURE LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; HIV-INACTIVATING PROTEIN; CYANOVIRIN-N; CRYSTAL-STRUCTURES; X-RAY; LECTIN; JACALIN; OLIGOSACCHARIDE; SPECIFICITIES; REFINEMENT AB The crystal structure of griffithsin, an antiviral lectin from the red alga Griffithsia sp., was solved and refined at 1.3 angstrom resolution for the free protein and 0.94 A for a complex with mannose. Griffithsin molecules form a domain-swapped dimer, in which two beta strands of one molecule complete a beta prism consisting of three four-stranded sheets, with an approximate 3-fold axis, of another molecule. The structure of each monomer bears close resemblance to jacalin-related lectins, but its dimeric structure is unique. The structures of complexes of griffithsin with mannose and N-acetylglucosamine defined the locations of three almost identical carbohydrate binding sites on each monomer. We have also shown that griffithsin is a potent inhibitor of the coronavirus responsible for severe acute respiratory syndrome (SARS). Antiviral potency of griffithsin is likely due to the presence of multiple, similar sugar binding sites that provide redundant attachment points for complex carbohydrate molecules present on viral envelopes. C1 NCI, Frederick Canc Res & Dev Ctr, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Werner H Kirsten Student Internship Program, Frederick, MD 21702 USA. Large Scale Biol Corp, Vacaville, CA 95688 USA. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov OI Palmer, Kenneth/0000-0002-2811-1111 FU Intramural NIH HHS NR 34 TC 82 Z9 83 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUL PY 2006 VL 14 IS 7 BP 1127 EP 1135 DI 10.1016/j.str.2006.05.017 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 066KO UT WOS:000239228500007 PM 16843894 ER PT J AU Haspel, N Zanuy, D Aleman, C Wolfson, H Nussinov, R AF Haspel, Nurit Zanuy, David Aleman, Carlos Wolfson, Haim Nussinov, Ruth TI De novo tubular nanostructure design based on self-assembly of beta-helical protein motifs SO STRUCTURE LA English DT Article ID AMYLOID FIBRIL FORMATION; MOLECULAR-DYNAMICS; HYDROPHOBIC CORE; HUMAN CALCITONIN; SEQUENCE; ORGANIZATION; RECOGNITION; NANOFIBERS; COMPUTER; SURFACES AB We present an approach for designing self-assembled ramostructures from naturally occurring building block segments obtained from native protein structures. We focus on structural motifs from left-handed beta-helical proteins. We selected 17 motifs. Copies of each of the motifs are stacked one atop the other. The obtained structures were simulated for long periods by using Molecular Dynamics to test their ability to retain their organization over time. We observed that a structural model based on the self-assembly of a motif from E. coli galactoside acetyltransferase produced a very stable tube. We studied the interactions that help maintain the conformational stability of the systems, focusing on the role of specific amino acids at specific positions. Analysis of these systems and a mutational study of selected candidates revealed that the presence of proline and glycine residues in the loops of P-helical structures greatly enhances the structural stability of the systems. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, SAIC Frederick Inc,Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. UPC, ETSEIB, Dept Chem Engn, E-08028 Barcelona, Spain. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, SAIC Frederick Inc,Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011; Zanuy, David/G-3930-2014; Haspel, Nurit/D-1961-2017 OI Zanuy, David/0000-0001-7704-2178; FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 40 TC 31 Z9 32 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUL PY 2006 VL 14 IS 7 BP 1137 EP 1148 DI 10.1016/j.str.2006.05.016 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 066KO UT WOS:000239228500008 PM 16843895 ER PT J AU Pluta, RM Oldfield, EH AF Pluta, Ryszard M. Oldfield, Edward H. TI Sodium nitrite as a therapeutic agent for central nervous system diseases SO SURGICAL NEUROLOGY LA English DT Article ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; DELAYED CEREBRAL VASOSPASM; CONTROLLED-RELEASE; ENDOTHELIAL-CELLS; OXIDE DONOR; PREVENTION; BLOOD; DEOXYHEMOGLOBIN; REPERFUSION; SYNTHASE C1 NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. EM oldfielde@ninds.nih.gov NR 31 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD JUL PY 2006 VL 66 IS 1 BP 5 EP 10 DI 10.1016/j.surneu.2005.10.017 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 061TN UT WOS:000238895600003 PM 16793425 ER PT J AU Libutti, SK Alexander, HR AF Libutti, Steven K. Alexander, H. Richard, Jr. TI Gastrinoma: Sporadic and familial disease SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ENDOCRINE NEOPLASIA TYPE-1; ISLET CELL TUMORS; SURGICAL-MANAGEMENT; PROGNOSTIC-FACTORS; NATURAL-HISTORY; LONG-TERM; LOCALIZATION; METASTASES AB The increased acid secretion as well as its consequences can be well controlled with medical therapy in patients with gastrinoma. The role of surgery has therefore shifted to the resection of primary tumors to prevent metastatic spread as well as the management of symptomatic metastases. Advanced imaging techniques have helped to make this possible by allowing the detection of occult gastrinomas. C1 NCI, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Maryland, Dept Surg, Baltimore, MD 21201 USA. RP Libutti, SK (reprint author), NCI, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res, CRC 4-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov NR 58 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2006 VL 15 IS 3 BP 479 EP + DI 10.1016/j.soc.2006.05.001 PG 19 WC Oncology; Surgery SC Oncology; Surgery GA 101RL UT WOS:000241758000004 PM 16882493 ER PT J AU Niederhuber, JE Fojo, T AF Niederhuber, John E. Fojo, Tito TI Treatment of metastatic disease in patients with neuroendocrine tumors SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ISLET-CELL-CARCINOMA; HEPATIC ARTERIAL CHEMOEMBOLIZATION; ENDOCRINE PANCREATIC TUMORS; TARGETED RADIONUCLIDE THERAPY; LIVER METASTASES; PHASE-II; SOMATOSTATIN ANALOGS; ANTITUMOR-ACTIVITY; BONE METASTASES; GASTROENTEROPANCREATIC TUMORS AB Gastroenteropancreatic neuroendocrine tumors (GENTs) comprise a heterogeneous group of relatively uncommon neoplasms with a yearly incidence rate of 1.2 to 3.0 per 100,000 population. These tumors share numerous histologic and biologic features, allowing their consideration as a common entity. They are postulated to arise from neuroendocrine cells, but most are not from neural crest origin. Their predominant site of origin is the gastrointestinal tract, where most involve the small intestine and appendix, but are also found in the adrenal medulla, bronchopulmonary system, pancreas, thyroid, parathyroid, and paraganglia cells. A common feature is their often indolent course, but some tumors are poorly differentiated and behave aggressively. This article addresses the surgical management of endocrine malignancies and the treatment of metastatic disease in patients with neuroendocrine tumors. C1 NCI, Med Oncol Branch & Affiliates, Bethesda, MD 20892 USA. RP Niederhuber, JE (reprint author), NCI, Med Oncol Branch & Affiliates, 31 Ctr Dr,Room 11A48, Bethesda, MD 20892 USA. EM niederj@mail.nih.gov NR 87 TC 8 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2006 VL 15 IS 3 BP 511 EP + DI 10.1016/j.soc.2006.05.004 PG 24 WC Oncology; Surgery SC Oncology; Surgery GA 101RL UT WOS:000241758000006 PM 16882495 ER PT J AU Cohen, RM Carson, RE Filbey, F Szczepanik, J Sunderland, T AF Cohen, RM Carson, RE Filbey, F Szczepanik, J Sunderland, T TI Age and APOE-epsilon 4 genotype influence the effect of physostigmine infusion on the in-vivo distribution volume of the muscarinic-2-receptor dependent tracer [F-18]FP-TZTP SO SYNAPSE LA English DT Article DE PET; brain imaging; cholinergic ID CHOLINE-ACETYLTRANSFERASE ACTIVITY; POSITRON-EMISSION-TOMOGRAPHY; APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; SENILE DEMENTIA; BRAIN; ABNORMALITIES; BINDING; ALLELE; MEMORY AB The apolipoprotein E-epsilon 4 allele (APOE-epsilon 4) confers greater susceptibility to age-related memory disorders. Abnormalities in the cholinergic system are likely contributors to these disorders with both age and APOE-epsilon 4 genotype modifying behavioral and physiological responses to drugs that alter cholinergic pathway function. Recently, we reported a greater in vivo distribution volume of the F-18 labeled muscarinic-2 (M2) selective agonist, 3-(3-(3-[F-18]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([F-18]FP-TZTP), in aging healthy subjects with an APOE-epsilon 4 allele. To examine the effects of aging and the APOE-epsilon 4 allele on the response of the muscarinic component of cholinergic pathway to pharmacologic augmentation, two [F-18]FP-TZTP PET scans were conducted in 19 subjects varying in age from 22 to 74 years, the first served as baseline for the second scan that was performed while the subjects were either infused with saline (n = 6) or with the acetylcholinesterase inhibitor physostigmine (6 with an APOE-epsilon 4 allele and 7 without an APOE-epsilon 4 allele). Using a multiple regression analysis, both AGE (beta = 0.621 +/- 0.135, B = 0.353 +/- 0.077, t(10) = 4.61, P < 0.001) and APOE-epsilon 4 genotype (beta = 0.742, B = 14.8 +/- 2.69, t(10) = 5.51, P < 0.0003) were found to be significant contributors to subject response to physostigmine. The adjusted R-2 for the model as a whole was 0.786 (F(2,10) = 23.00, P < 0.0002) with both increasing age and the presence of the APOE-epsilon 4 allele modifying the response to physostigmine in the direction of larger decreases in [F-18]FP-TZTP distribution volumes in all brain regions examined. The findings, particularly the absence of an interaction between AGE and APOE-epsilon 4 genotype, contribute to the growing body of evidence that suggests that the APOE-epsilon 4 genotype is likely to contribute to brain structure and function prior to aging. C1 NIMH, Gen Psychiat Pranch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Positron Emiss Tomography Dept, Bethesda, MD 20892 USA. RP Cohen, RM (reprint author), Cedars Sinai Med Ctr, Dept Psychiat, Thalians E101,8730 Alden Dr, Los Angeles, CA 90048 USA. EM cohenr@cshs.org RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 41 TC 11 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2006 VL 60 IS 1 BP 86 EP 92 DI 10.1002/syn.20276 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 043GK UT WOS:000237588000008 PM 16598702 ER PT J AU Mundinger, GS Espina, V Liotta, LA Petricoin, EF Calvo, KR AF Mundinger, Gerhard S. Espina, Virginia Liotta, Lance A. Petricoin, Emanuel F., III Calvo, Katherine R. TI Clinical phosphoproteomic profiling for personalized targeted medicine using reverse phase protein microarray SO TARGETED ONCOLOGY LA English DT Review DE Proteomics; Reverse phase protein microarray; Signal transduction profiling; Combinatorial therapy; Targeted therapy; Personalized molecular medicine AB Healthcare providers are increasingly incorporating information gleaned from genomics and proteomics in the diagnosis and treatment of cancer. These lines of inquiry are providing greater insight into why patients with similar histological tumor classification and staging often demonstrate dissimilar clinical outcomes, and are illuminating distinct diagnostic subgroups that are more responsive to specific treatment modalities. Clearer understanding of genes, gene products, and signaling pathways holds great promise for the personalization of molecular medicine. While the origins of oncologic disease are genetically encoded, the disease process is largely mediated through altered protein function. Recent investigations suggest that each individual patient's tumor possesses unique kinase-driven cell signaling derangements, and that these derangements derive, in part, from the tumor's relationship with its host microenvironment. Identification of signaling derangements and mapping functional protein-protein interactions via phosphoproteomic profiling offers great promise for the precise targeting of therapeutic agents, identifying new therapeutic targets, devising effective combinatorial therapies, monitoring treatment efficacy and toxicity, and ultimately predicting treatment outcome. This review focuses on advances in clinical phosphoproteomic profiling of cancer using the emerging technology of reverse phase protein microarrays, and highlights the translational roles this technology is playing in laying the foundations for personalized molecular therapeutics. C1 [Mundinger, Gerhard S.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Espina, Virginia; Liotta, Lance A.; Petricoin, Emanuel F., III] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA. [Calvo, Katherine R.] NCI, Pathol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Mundinger, GS (reprint author), Johns Hopkins Univ, Sch Med, 733 N Broadway,Suite 137, Baltimore, MD 21205 USA. EM gsm@jhmi.edu; vespina@gmu.edu; lliotta@gmu.edu; epetrico@gmu.edu; calvok@mail.nih.gov RI Calvo, Katherine/A-8109-2009; OI Calvo, Katherine/0000-0002-0771-4191; Espina, Virginia/0000-0001-5080-5972 NR 210 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 J9 TARGET ONCOL JI Target. Oncol. PD JUL PY 2006 VL 1 IS 3 BP 151 EP 167 DI 10.1007/s11523-006-0025-2 PG 17 WC Oncology SC Oncology GA V04JD UT WOS:000207053800005 ER PT J AU Nazareth, RA Tomaz, LS Ortiz-Costa, S Atella, GC Ribeiro, JMC Francischetti, IMB Monteiro, RQ AF Nazareth, Romulo A. Tomaz, Luana S. Ortiz-Costa, Susana Atella, Georgia C. Ribeiro, Jose M. C. Francischetti, Ivo M. B. Monteiro, Robson Q. TI Antithrombotic properties of ixolaris, a potent inhibitor of the extrinsic pathway of the coagulation cascade SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE anticoagulant; ixolaris; venous thrombosis; factor Xa; tissue factor; tick saliva; Ixodes scopularis ID ANTICOAGULANT PROTEIN C2; TISSUE FACTOR; BLOOD-COAGULATION; FACTOR-XA; THROMBOSIS; HEPARIN; GLYCOSAMINOGLYCANS; COMPLEX; BINDING; MODELS AB Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scopularis that presents extensive sequence homology to TFPI. It binds to FXa or FX as scaffolds and inhibits tissue factor/ FVIIa complex (extrinsic Xnase). Differently from TFPI, ixolaris does not bind to the active site cleft of FXa. Instead, complex formation is mediated by the FXa heparin-binding exosite,which may also results in decreased FXa activity into the prothrombinase complex. In this report,we show that recombinant I-125-ixolaris interacts with rat and human FX in plasma and prolongs the prothrombin time (PT) and activated partial thromboplastin time (aPTT) in vitro.We have also investigated the effects of ixolaris in vivo, using a venous thrombosis model. Subcutaneous (s.c.) or intravenous (i.v.) administration of ixolaris in rats caused a dose-dependent reduction in thrombus formation, with complete inhibition attained at 20 mu g/kg and 10 mu g/kg, respectively.Antithrombotic effects were observed 3 h after s.c. administration of ixolaris and lasted for 24 h thereafter. Ex vivo experiments showed that ixolaris (up to 100 mu g/kg) did not affect the aPTT while the PT was increased by similar to 0.4-fold at the highest ixolaris concentration. Remarkably, effective antithrombotic doses of ixolaris (20 mu g/kg) was not associated with bleeding which was significant only at higher doses of the anticoagulant (40 mu g/kg). Our experiments demonstrate that ixolaris is an effective and possibly safe antithrombotic agent in vivo. C1 UFRJ, Inst Bioquim Med, CCS, BR-21941590 Rio De Janeiro, Brazil. UFRJ, Inst Nutr, CCS, BR-21941590 Rio De Janeiro, Brazil. NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Monteiro, RQ (reprint author), UFRJ, Inst Bioquim Med, CCS, Cidade Univ,Ilha Fundao Ave Bauhinia 400, BR-21941590 Rio De Janeiro, Brazil. EM robsonqm@bioqmed.ufrj.br RI Monteiro, Robson/B-8007-2014; OI Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999] NR 24 TC 39 Z9 40 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2006 VL 96 IS 1 BP 7 EP 13 DI 10.1160/TH06-02-0105 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 064CA UT WOS:000239065600003 PM 16807644 ER PT J AU Coppotelli, G Summers, A Chidakel, A Ross, JM Celi, FS AF Coppotelli, Giuseppe Summers, Aaron Chidakel, Aaron Ross, Jaime M. Celi, Francesco S. TI Functional characterization of the 258 A/G (D2-ORFa-Gly3Asp) human type-2 deiodinase polymorphism: A naturally occurring variant increases the enzymatic activity by removing a putative repressor site in the 5 ' UTR of the gene SO THYROID LA English DT Article ID THYROID-HORMONE ACTIVATION; IODOTHYRONINE DEIODINASE; STRUCTURAL ORGANIZATION; 5'-DEIODINASE; EXPRESSION; ROLES; ASSOCIATION; RESISTANCE; THYROXINE; SECRETION AB Objective: 5' deiodination of thyroid hormone represents an important step in the modulation of the hormonal message. Previous studies indicate that the naturally occurring polymorphism located in 5'-untranslated region of the gene, 258 A/G, is associated with a decrease in circulating T4/T3 ratio, suggesting an increased gene expression. The aim of this study was to characterize the gene variant in vitro. Design: This was designed as an in vitro study. Main outcome: The wild-type and mutant promoters were cloned into a reporter vector and transfected into HEK-293, GH3, and H3B cells. Compared to the 258G wild-type allele, the 258A variant had an increased basal activity in all the cell lines (HEK-293 258A 13998 +/- 371.9 RLU vs. 258G 5593 +/- 124.2 RLU, p < 0.0001). Electrophoresis mobility shift assay (EMSA) experiments were performed with nuclear extracts obtained from HEK-293 cells and from human thyroid, muscle, and liver. The EMSA experiments showed that the 258A variant decreased the binding ability of a nuclear protein in HEK-293 cells, thyroid, and muscle. No specific binding was observed in liver nuclei. Conclusion: These data suggest that the increase in gene transcription induced by the 258A polymorphism could be mediated by reduction in the binding ability of a putative nuclear repressor. C1 NIDDKD, Clin Endocrinol Branch, NIH, CRC, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Celi, FS (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, CRC, Bldg 10,Rm 6-3940,10 Ctr Dr MSC 1613, Bethesda, MD 20892 USA. EM fc93a@nih.gov RI Ross, Jaime/A-6893-2012 FU Intramural NIH HHS NR 30 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 2006 VL 16 IS 7 BP 625 EP 632 DI 10.1089/thy.2006.16.625 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 075LG UT WOS:000239885900001 PM 16889485 ER PT J AU Li, WJ Jiang, YJ Tuan, RS AF Li, Wan-Ju Jiang, Yi Jen Tuan, Rocky S. TI Chondrocyte phenotype in engineered fibrous matrix is regulated by fiber size SO TISSUE ENGINEERING LA English DT Article ID POLYMER-DEMIXED NANOTOPOGRAPHY; MESENCHYMAL STEM-CELLS; ARTICULAR-CARTILAGE; EXTRACELLULAR-MATRIX; NANOPHASE CERAMICS; ENHANCED FUNCTIONS; IN-VITRO; BEHAVIOR; SCAFFOLDS; OSTEOBLASTS AB A biomaterial scaffold acting as a functional substitute for the native extracellular matrix provides space for cell accommodation. In this study, we seeded chondrocytes, isolated from 4- to 6-month-old calves, in 2 types of poly(L-lactide) scaffolds, composed of micro- and nanofibers, and compared the effects on cellular activities. Scanning electron microscopy revealed a well-spread morphology for chondrocytes grown on microfibers. In contrast, chondrocytes on the nanofibers were found to have a rounded morphology and displayed a disorganized actin cytoskeletal structure compared to the organized cytoskeleton seen in well-spread chondrocytes culture on the microfibrous scaffold. Both scaffolds supported chondrocyte proliferation, with a higher rate seen in cultures in nanofibrous scaffold. Quantitative reverse transcription-polymerase chain reaction analysis showed that both cultures supported expression of collagen types I and II and aggrecan. Biochemical analysis showed a higher level of sulfated glycosaminoglycan in the nanofiber culture, confirmed by more intense alcian blue histologic staining. The nanofiber cultures also showed higher immunostaining for collagen types II and IX, aggrecan, and cartilage proteoglycan link protein. Based on these results, we conclude that chondrocytes respond differently to fibrous scaffolds of varying diameters, and that the scaffolds made of nanofibrous biomaterial promote efficient cell-based cartilage tissue engineering. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1503,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov RI Li, Wan-Ju/A-7002-2008 FU Intramural NIH HHS NR 41 TC 149 Z9 152 U1 4 U2 24 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUL PY 2006 VL 12 IS 7 BP 1775 EP 1785 DI 10.1089/ten.2006.12.1775 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 071BK UT WOS:000239571800006 PM 16889508 ER PT J AU Kissling, GE Bernheim, NJ Hawkins, WE Wolfe, MJ Jokinen, MP Smith, CS Herbert, RA Boorman, GA AF Kissling, GE Bernheim, NJ Hawkins, WE Wolfe, MJ Jokinen, MP Smith, CS Herbert, RA Boorman, GA TI The utility of the guppy (Poecilia reticulata) and medaka (Oryzias latipes) in evaluation of chemicals for carcinogenicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE bioassays; small fish models; medaka; guppy; rodent carcinogens; nitromethane; propanediol; trichloropropane ID WATER MUTAGEN 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE; AQUARIUM FISH MODELS; JAPANESE MEDAKA; ENVIRONMENTAL CARCINOGENESIS; RODENT CARCINOGENICITY; RAINBOW-TROUT; TOXICITY; MUTATIONS; LIVER; DIETHYLNITROSAMINE AB There has been considerable interest in the use of small fish models for detecting potential environmental carcinogens. In this study, both guppies (Poecilia reticulata) and medaka (Oryzias latipes) were exposed in the aquaria water to three known rodent carcinogens for up to 16 months. Nitromethane, which caused mammary gland tumors by inhalation exposure in female rats, harderian gland and lung tumors in male and female mice, and liver tumors in female mice by inhalation, failed to increase tumors in either guppies or medaka. Propanediol, which when given in the feed was a multisite carcinogen in both sexes of rats and mice, caused increased liver tumors in male guppies and male medaka. There was reduced survival in female guppies and no increased tumors in female medaka. 1,2,3-Trichloropropane, which when administered by oral gavage was a multisite carcinogen in both sexes of rats and mice, caused an increased incidence of tumors in the liver of both male and female guppies and medaka and in the gallbladder of male and female medaka. The results of this study demonstrate that for these three chemicals, under these specific exposure conditions, the fish appear less sensitive and have a narrower spectrum of tissues affected than rodents. These results suggest that fish models are of limited utility in screening unknown chemicals for potential carcinogenicity. C1 Natl Inst Environm Hlth Sci, Environm Med & Dis Program, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS 39566 USA. Expt Pathol Labs Inc, Herndon, VA 20172 USA. Pathol Associates Inc, Cary, NC 27513 USA. RP Kissling, GE (reprint author), Natl Inst Environm Hlth Sci, Environm Med & Dis Program, MD A3-03,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kissling@niehs.nih.gov FU NIEHS NIH HHS [N01 ES 35371, N01-ES-35371] NR 39 TC 9 Z9 10 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2006 VL 92 IS 1 BP 143 EP 156 DI 10.1093/toxsci/kfj181 PG 14 WC Toxicology SC Toxicology GA 058FH UT WOS:000238650400016 PM 16581948 ER PT J AU Grose, HL Byrne, KM Salata, JM Rentas, FJ Stroncek, DF AF Grose, HL Byrne, KM Salata, JM Rentas, FJ Stroncek, DF TI In vitro variables of red blood cell components collected by apheresis and frozen 6 and 14 days after collection SO TRANSFUSION LA English DT Article ID 40-PERCENT WT/VOL GLYCEROL; AS-3; 4-DEGREES-C; ACP-215; DEGLYCEROLIZATION; SURVIVAL; STORAGE; RBCS AB An automated cell processing system (ACP 215, Haemonetics Corp.) can be used for the glycerolization and deglycerolization of RBC components, but the components must be 6 or fewer days old. Depending on the anticoagulant (CP2D)/additive solution (AS) used, deglycerolized RBCs can be stored at 1 to 6 degrees C for up to 14 days. This study evaluated in vitro variables of apheresis RBC stored for 6 and 14 days at 1 to 6 degrees C before glycerolization and 14 days after deglycerolization. Two units of CP2D/AS-3 leukoreduced RBCs were collected by apheresis from seven donors. One unit was glycerolized and frozen 6 days and the other 14 days after collection. All units were deglycerolized with the ACP 215 and stored at 1 to 6 degrees C for 14 days in AS-3. Several in vitro variables were evaluated during postdeglycerolization storage. All components had postdeglycerolization RBC recoveries greater than 81 percent and osmolalities of less than 400 mOsm per kg. No significant differences were noted in potassium and supernatant hemoglobin after 14 days of postdeglycerolization storage between RBCs frozen at 6 and 14 days after collection. After 14 days of postdeglycerolization storage, however, the pH, lactate, and ATP levels were slightly lower in RBCs frozen after 14 days. The ACP 215 can be used to glycerolize and deglycerolize apheresis RBC components that are up to 14 days of age. It is likely that apheresis components glycerolized at 14 days of age or less can be stored up to 14 days in AS-3 after deglycerolization, but this should be confirmed with in vivo survival studies. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RP Byrne, KM (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711,10 Ctr Dr MSC-1184, Bethesda, MD 20892 USA. EM kbyrne@cc.nih.gov NR 7 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2006 VL 46 IS 7 BP 1178 EP 1183 DI 10.1111/j.1537-2995.2006.00868.x PG 6 WC Hematology SC Hematology GA 055YQ UT WOS:000238487700018 PM 16836565 ER PT J AU Tran, MH Fadeyi, E Scheinberg, P Klein, HG AF Tran, MH Fadeyi, E Scheinberg, P Klein, HG TI Apparent hemolysis following intravenous antithymocyte globulin treatment in a patient with marrow failure and a paroxysmal nocturnal hemoglobinuria clone SO TRANSFUSION LA English DT Article ID RED-CELLS; TRANSFUSION; DEFICIENT; PROTEINS AB Antithymocyte globulin (ATG) is a commonly used medication in the treatment of aplastic anemia. Although serum sickness has been described with the use of ATG, few cases of acute intravascular hemolysis have been reported. We report a case of apparent ATG-related hemolysis in a patient with aplastic anemia and a paroxysmal nocturnal hemoglobinuria (PNH) clone. A 62-year-old, group A, RhoD+ man with aplastic anemia and an 11.6 percent glycosylphosphatidylinositol (GPI)-anchored protein-negative population of red cells (RBCs), representing approximately 190 mL of his RBC volume, and 90 percent GPI-negative neutrophils were scheduled to receive equine ATG at 40 mg per kg per day for 4 days. After the first infusion, he developed a 1.6 g per dL decline in hemoglobin concentration and an increase in serum lactate dehydrogenase (normal, 113-226 U/L) from 284 to 1127 U per L. The hemolytic process was complicated by acute renal failure characterized by an increase in serum creatinine from 0.9 to 4.2 mg per dL and the appearance of dark-colored urine. Pre- and post-ATG direct antiglobulin tests were negative. The temporal association of intravenous ATG to lysis of complement-sensitive RBCs suggests a causal relationship. Although intravascular hemolysis after ATG administration appears to be uncommon, the clinical consequences may be severe, and determining the pathophysiology may yield clues to the mechanism of intravascular hemolysis. C1 NIH, Mark O Hatfield Clin Res Ctr, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Tran, MH (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM tranmh@cc.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 NR 9 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2006 VL 46 IS 7 BP 1244 EP 1247 DI 10.1111/j.1537-2995.2006.00877.x PG 4 WC Hematology SC Hematology GA 055YQ UT WOS:000238487700027 PM 16836574 ER PT J AU Zerhouni, EA Alving, B AF Zerhouni, Elias A. Alving, Barbara TI Clinical and Translational Science Awards: a framework for a national research agenda SO TRANSLATIONAL RESEARCH LA English DT Editorial Material C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NR 1 TC 45 Z9 46 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 J9 TRANSL RES JI Transl. Res. PD JUL PY 2006 VL 148 IS 1 BP 4 EP 5 DI 10.1016/j.lab.2006.05.001 PG 2 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 084ML UT WOS:000240537000002 PM 16887491 ER PT J AU Kang, JG Patino, WD Matoba, S Hwang, PM AF Kang, JG Patino, WD Matoba, S Hwang, PM TI Genomic analysis of circulating cells: A window into atherosclerosis SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID BLOOD MONONUCLEAR-CELLS; C-REACTIVE PROTEIN; GENE-EXPRESSION; SERIAL ANALYSIS; BREAST-CANCER; MONOCYTES; DISEASE; INFLAMMATION; ANNOTATION; MECHANISMS AB Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments utilizing diseased tissue or surrogate specimens. This review details the rationale and findings of a study utilizing freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched healthy subjects. By querying this cardiovascular tissue surrogate, the messenger RNA levels of the Finkel-Biskis-Jenkins osteosarcoma gene in circulating monocytes were found to correlate with atherosclerosis severity in patients and with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy hi healthy subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate our report. They also provide us with insights into pathogenesis that may impact future translational applications. C1 NHLBI, Clin Res Ctr, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Hwang, PM (reprint author), NHLBI, Clin Res Ctr, Cardiovasc Branch, NIH, Bldg 10,Room 5-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 41 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JUL PY 2006 VL 16 IS 5 BP 163 EP 168 AR PII S1050-1738(06)00047-8 DI 10.1016/j.tcm.2006.03.006 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 058WM UT WOS:000238695300005 PM 16781950 ER PT J AU Balla, A Balla, T AF Balla, Andras Balla, Tamas TI Phosphatidylinositol 4-kinases: old enzymes with emerging functions SO TRENDS IN CELL BIOLOGY LA English DT Review ID NEURONAL CALCIUM SENSOR-1; PLECKSTRIN-HOMOLOGY-DOMAIN; CANINE KIDNEY-CELLS; SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; GOLGI-COMPLEX; PHOSPHOINOSITIDE KINASES; PHOSPHOLIPID KINASE; LIPID KINASE; YEAST AB Phosphoinositides account for only a tiny fraction of cellular phospholipids but are extremely important in the regulation of the recruitment and activity of many signaling proteins in cellular membranes. Phosphatidylinositol (PtdIns) 4-kinases generate PtdIns 4-phosphate, the precursor of important regulatory phosphoinositides but also an emerging regulatory molecule in its own right. The four mammalian PtdIns 4-kinases regulate a diverse array of signaling events, as well as vesicular trafficking and lipid transport, but the mechanisms by which their lipid product PtdIns 4-phosphate controls these processes is only beginning to unfold. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793 FU Intramural NIH HHS NR 86 TC 186 Z9 192 U1 4 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUL PY 2006 VL 16 IS 7 BP 351 EP 361 DI 10.1016/j.tcb.2006.05.003 PG 11 WC Cell Biology SC Cell Biology GA 071SL UT WOS:000239622100004 PM 16793271 ER PT J AU Wolf, YI AF Wolf, Yuri I. TI Coping with the quantitative genomics 'elephant': the correlation between the gene dispensability and evolution rate SO TRENDS IN GENETICS LA English DT Article ID PROTEIN EVOLUTION; LEVEL AB Early studies suggested that proteins with a greater contribution to the fitness of an organism evolve more slowly than less 'important' proteins. Recent articles by two research groups highlight the long-standing controversy about the genome-wide relationships between the measures of evolution rate, protein abundance and the fitness effect of gene disruption. These studies highlight the need for truly multidimensional approaches to the issues of quantitative genomics. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wolf, YI (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM wolf@ncbi.nlm.nih.gov NR 19 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2006 VL 22 IS 7 BP 354 EP 357 DI 10.1016/j.tig.2006.04.009 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 072PE UT WOS:000239684500003 PM 16697070 ER PT J AU Lobanov, AV Kryukov, GV Hatfield, DL Gladyshev, VN AF Lobanov, Alexey V. Kryukov, Gregory V. Hatfield, Dolph L. Gladyshev, Vadirn N. TI Is there a twenty third amino acid in the genetic code? SO TRENDS IN GENETICS LA English DT Article ID TRANSFER-RNA GENES; SEQUENCES; PROGRAM; UAG AB The universal genetic code includes 20 common amino acids. In addition, selenocysteine (Sec) and pyrrolysine (Pyl), known as the twenty first and twenty second amino acids, are encoded by UGA and UAG, respectively, which are the codons that usually function as stop signals. The discovery of Sec and Pyl suggested that the genetic code could be further expanded by reprogramming stop codons. To search for the putative twenty third amino acid, we employed various tRNA identification programs that scanned 16 archaeal and 130 bacterial genomes for tRNAs with anticodons corresponding to the three stop signals. Our data suggest that the occurrence of additional amino acids that are widely distributed and genetically encoded is unlikely. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013 FU NIGMS NIH HHS [GM061603] NR 10 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2006 VL 22 IS 7 BP 357 EP 360 DI 10.1016/j.tig.2006.05.002 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 072PE UT WOS:000239684500004 PM 16713651 ER PT J AU Lim, JK Glass, WG McDermott, DH Murphy, PM AF Lim, Jean K. Glass, William G. McDermott, David H. Murphy, Philip M. TI CCR5: no longer a 'good for nothing' gene - chemokine control of West Nile virus infection SO TRENDS IN IMMUNOLOGY LA English DT Review ID CD8(+) T-CELLS; MULTIPLE-SCLEROSIS; TRYPANOSOMA-CRUZI; DELETION ALLELE; HIV-1 ENTRY; RECEPTOR 5; RNASE-L; DISEASE; ENCEPHALITIS; LETHAL AB The chemokine receptor CCR5 was identified in 1996 as a crucial host factor exploited by HIV for cell entry. CCR5 presumably functions normally in antimicrobial host defense because it generally mediates leukocyte chemotactic responses; however, evidence of antimicrobial functions for CCR5 in humans has been elusive. Recently, genetic analyses in mice and humans have provided strong evidence for the CCR5 control of infection by West Nile virus (WNV), a re-emerging pathogen capable of causing fatal encephalitis. Thus, the same receptor can benefit or harm the host, depending on the virus. Although CCR5 might be a logical target for new drug development in HIV/AIDS, the benefits of blocking CCR5 could carry the cost of an increased risk of WNV disease in co-infected patients. C1 NIAID, Lab Mol Immunol, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. Centocor Global R&D, Infect Dis, Radnor, PA 19087 USA. RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. EM pmm@nih.gov OI McDermott, David/0000-0001-6978-0867 NR 53 TC 71 Z9 78 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JUL PY 2006 VL 27 IS 7 BP 308 EP 312 DI 10.1016/j.it.2006.05.007 PG 5 WC Immunology SC Immunology GA 068JI UT WOS:000239369400003 PM 16753343 ER PT J AU Subbarao, K Roberts, A AF Subbarao, Kanta Roberts, Anjeanette TI Is there an ideal animal model for SARS? SO TRENDS IN MICROBIOLOGY LA English DT Review ID ACUTE RESPIRATORY SYNDROME; SYNDROME-ASSOCIATED CORONAVIRUS; HUMAN MONOCLONAL-ANTIBODY; GOLDEN SYRIAN-HAMSTERS; PROTECTIVE IMMUNITY; NEUTRALIZING ANTIBODY; SPIKE GLYCOPROTEIN; AFRICAN-GREEN; MICE; INFECTION AB The outbreak of severe acute respiratory syndrome (SAIRS) in 2003 was controlled by public health measures at a time when specific interventions such as antiviral drugs, vaccines and immunotherapy were not available. Since then, several animal models have been developed for the study of SARS and, although no model replicates the human disease in all aspects, the use of animal models for SARS has led to the establishment of several important principles for vaccine and immunotherapy. Consistency and reproducibility of findings in a given model must be demonstrated to establish the superiority of one model over others. Here, we suggest aspects of an ideal animal model for studies of SARS pathogenesis and vaccine development and present our assessment of the strengths and limitations of the current animal models for SARS. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS NR 39 TC 46 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JUL PY 2006 VL 14 IS 7 BP 299 EP 303 DI 10.1016/j.tim.2006.05.007 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 068JJ UT WOS:000239369500005 PM 16759866 ER PT J AU Smith, GH AF Smith, Gilbert H. TI Mammary stem cells come of age, prospectively SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID EPITHELIAL-CELLS; PROGENITOR CELLS; GLAND; DIFFERENTIATION; BETA-1-INTEGRIN; MORPHOGENESIS; INTEGRIN; REVEALS; MODEL AB Two recent reports have contributed direct evidence for the existence of a pluripotent mouse mammary epithelial stem cell. In both reports, the investigators have prospectively isolated an enriched fraction of mammary stem cells using fluorescence-activated cell sorting from freshly dispersed epithelial cells. This fraction of cells, upon transplantation in limiting dilution (in some cases as a single cell), produces complete mammary development within the host mammary fat pad. These studies extend and confirm earlier work that demonstrated that retroviral-tagged mammary fragments produce complete functional mammary glands comprising their clonal progeny upon fat-pad transplantation. This technical advance opens the possibility to use similar methodologies to isolate and characterize human breast epithelial stem cells, and elucidate their role in regeneration and neoplasia. C1 NCI, Lab Mammary Biol & Tumorigenesis, Canc Res Ctr, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Lab Mammary Biol & Tumorigenesis, Canc Res Ctr, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 17 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUL PY 2006 VL 12 IS 7 BP 287 EP 289 DI 10.1016/j.molmed.2006.05.003 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 072WN UT WOS:000239703800001 PM 16750424 ER PT J AU de Haan, M Mishkin, M Baldeweg, T Vargha-Khadem, F AF de Haan, Michelle Mishkin, Mortimer Baldeweg, Torsten Vargha-Khadem, Faraneh TI Human memory development and its dysfunction after early hippocampal injury SO TRENDS IN NEUROSCIENCES LA English DT Article; Proceedings Paper CT 4th INMED/TINS Conference on Nature and Nurture in Brain Development and Neurological Disorders CY SEP 04-07, 2005 CL La Ciotat, FRANCE SP INMED, TINS ID MEDIAL TEMPORAL-LOBE; VISUAL RECOGNITION MEMORY; TERM EXPLICIT MEMORY; DECLARATIVE MEMORY; DEFERRED IMITATION; EPISODIC MEMORY; 1ST YEAR; AUTOBIOGRAPHICAL MEMORY; CHILDHOOD AMNESIA; SEMANTIC MEMORY AB Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue Nature and nurture in brain development and neurological disorders, based on presentations at the annual INMED/TINS symposium (http://inmednet.com/). C1 Univ London, Inst Child Hlth, Dev Cognit Neurosci Unit, London WC1N 1EH, England. NIMH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP de Haan, M (reprint author), Univ London, Inst Child Hlth, Dev Cognit Neurosci Unit, 30 Guilford St, London WC1N 1EH, England. EM m.de-haan@ich.ucl.ac.uk RI de Haan, Michelle/C-5070-2008; Vargha-Khadem, Faraneh/C-2558-2008 FU Medical Research Council [G0300117] NR 110 TC 51 Z9 51 U1 8 U2 23 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2006 VL 29 IS 7 BP 374 EP 381 DI 10.1016/j.tins.2006.05.008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 075UB UT WOS:000239909600005 PM 16750273 ER PT J AU Hu, CH Liu, RB Zhou, QF Yen, J Shung, KK AF Hu, Chang-Hong Liu, Ruibin Zhou, Qifa Yen, Jesse Shung, K. Kirk TI Coded excitation using biphase-coded pulse with mismatched filters for high-frequency ultrasound imaging SO ULTRASONICS LA English DT Article DE coded excitation; mismatched filter; high-frequency ultrasound ID DIGITAL BEAMFORMER; REAL-TIME; PART II; ARRAY; SYSTEM; DESIGN; PRINCIPLES; SIGNALS AB A scheme of using phase-coded excitation and mismatched filter compression for high-frequency ultrasound imaging is presented in this paper. Biphase-coded pulses were constructed to excite the transducer. Received signals were compressed with mismatched filters optimized by minimizing peak-sidelobe-level (PSL). Both simulation and experiments were carried out to demonstrate the advantage of this technique. The simulation results demonstrated a possible sidelobe reduction (<-90 dB) with a slightly decrease of the signal-to-noise ratio of less than 1 dB compared with the compression using matched filters alone. The experimental results showed about 14 dB SNR improvement as well as -40 dB sidelobe level when the Barker-13 code excitation with 3-cycle sinusoidal wave carrier was used. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ So Calif, Biomed Engn Dept, Los Angeles, CA 90089 USA. Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Hu, CH (reprint author), Univ So Calif, Biomed Engn Dept, Los Angeles, CA 90089 USA. EM changhoh@usc.edu FU NIBIB NIH HHS [P41-EB2182] NR 23 TC 11 Z9 12 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0041-624X J9 ULTRASONICS JI Ultrasonics PD JUL PY 2006 VL 44 IS 3 BP 330 EP 336 DI 10.1016/j.ultras.2006.04.002 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 069JD UT WOS:000239441300012 PM 16714042 ER PT J AU Gozalo, AS Hoffmann, VJ Lambert, LE AF Gozalo, A. S. Hoffmann, V. J. Lambert, L. E. TI Ureteral fibroepithelial polyp in an owl monkey (Aotus nancymae) SO VETERINARY PATHOLOGY LA English DT Article DE Aotus; cebidae; fibroepithelial polyp; neoplasia; nonhuman primate; ureter AB Ureteral fibroepithelial polyps are benign mesodermal tumors in humans that occur predominantly in the proximal ureter. During a routine necropsy of a wild-caught, research naive, adult, male, Aotus nancymae, the left ureter just distal to the renal pelvis contained a pedunculated, lobulated neoplasm with a narrow stalk at the base projecting into the lumen. The left renal pelvis was found to be mildly dilated. The histologic characteristics of the ureteral mass were consistent with a fibroepithelial polyp. To our knowledge, this is the first report describing a ureteral fibroepithelial polyp in a nonhuman primate. C1 NIAID, Comparat Med Branch, NIH, SoBran Inc, Bethesda, MD 20892 USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, SoBran Inc, Bldg 14B S,Room 228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Intramural NIH HHS NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JUL PY 2006 VL 43 IS 4 BP 573 EP 575 DI 10.1354/vp.43-4-573 PG 3 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 067AK UT WOS:000239272200023 PM 16847004 ER PT J AU Alessandro, R Di Bella, MA Flugy, AM Fontana, S Damiani, F Corrado, C Colomba, P Todaro, M Russo, D Santoro, A Kohn, EC De Leo, G AF Alessandro, R Di Bella, MA Flugy, AM Fontana, S Damiani, F Corrado, C Colomba, P Todaro, M Russo, D Santoro, A Kohn, EC De Leo, G TI Comparative study of T84 and T84SF human colon carcinoma cells: in vitro and in vivo ultrastructural and functional characterization of cell culture and metastasis SO VIRCHOWS ARCHIV LA English DT Article DE colon carcinoma; tumor cells; ultrastructure; metastasis; apoptosis; Bcl-XL ID CANCER-CELLS; HUMAN-BREAST; MEMBRANE-VESICLES; BETA-CATENIN; MATRIX METALLOPROTEINASES; ELECTRON-MICROSCOPY; ENDOTHELIAL-CELLS; ADHESION; EXPRESSION; PROGRESSION AB To better understand the relationship between tumor heterogeneity, differentiation, and metastasis, suitable experimental models permitting in vitro and in vivo studies are necessary. A new variant cell line (T84SF) exhibiting an altered phenotype was recently selected from a colon cancer cell line (T84) by repetitive plating on TNF-alpha treated human endothelial cells and subsequent selection for adherent cells. The matched pair of cell lines provides a useful system to investigate the extravasation step of the metastatic cascade. Since analysis of morphological differences can be instructive to the understanding of metastatic potential of tumor cells, we compared the ultrastructural and functional phenotype of T84 and T84SF cells in vitro and in vivo. The reported ultrastructural features evidence differences between the two cell lines; selected cells showed a marked pleomorphism of cell size and nuclei, shape, and greater surface complexity. These morphological differences were also coupled with biochemical data showing a distinct tyrosine phosphorylation-based signaling, an altered localization of beta-catenin, MAPK, and AKT activation, as well as an increased expression in T84SF cells of Bcl-X-L, a major regulator of apoptosis. Therefore, these cell lines represent a step forward in the development of appropriate models in vitro and in vivo to investigate colon cancer progression. C1 Univ Palermo, Dipartimento Biopatol & Metodol Biomed, Sezione Biol & Genet, I-90133 Palermo, Italy. Univ Palermo, Dipartimento Discipline Chirurg Oncol, I-90133 Palermo, Italy. Ctr Nazl Ric, Ist Biomed & Immunol Mol Alberto Monroy, Palermo, Italy. AO V Cervello, Dipartimento Ric Clin & Biotecnol, Lab Ematol, Palermo, Italy. NCI, Mol Signalling Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Alessandro, R (reprint author), Univ Palermo, Dipartimento Biopatol & Metodol Biomed, Sezione Biol & Genet, Via Divisi 83, I-90133 Palermo, Italy. EM ricale@unipa.it OI Fontana, Simona/0000-0003-4681-2170 NR 57 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD JUL PY 2006 VL 449 IS 1 BP 48 EP 61 DI 10.1007/s00428-006-0179-4 PG 14 WC Pathology SC Pathology GA 058NF UT WOS:000238671000006 PM 16612624 ER PT J AU Schiffmann, R AF Schiffmann, R TI The significance of lysosomal inclusions in Fabry disease SO VIRCHOWS ARCHIV LA English DT Letter C1 NINDS, NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Schiffmann, R (reprint author), NINDS, NIH, Dev & Metab Neurol Branch, Bldg 10,Rm 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM SchiffmR@ninds.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD JUL PY 2006 VL 449 IS 1 BP 134 EP 134 DI 10.1007/s00428-006-0201-x PG 1 WC Pathology SC Pathology GA 058NF UT WOS:000238671000018 PM 16609905 ER PT J AU Wickerham, DL Costantino, JP Mamounas, EP Julian, TB AF Wickerham, D. Lawrence Costantino, Joseph P. Mamounas, Eleftherios P. Julian, Thomas B. TI The landmark surgical trials of the National Surgical Adjuvant Breast and Bowel Project SO WORLD JOURNAL OF SURGERY LA English DT Article ID COMPARING TOTAL MASTECTOMY; RANDOMIZED CLINICAL-TRIAL; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; SENTINEL-NODE BIOPSY; 20-YEAR FOLLOW-UP; RADICAL-MASTECTOMY; AXILLARY DISSECTION; PREOPERATIVE DOXORUBICIN; LOCOREGIONAL RECURRENCE; RADIATION-THERAPY AB In this paper we provide a summary of several of the completed and ongoing surgical trials of the National Surgical Adjuvant Breast and Bowel Project, one of the cancer cooperative trials groups supported by the US National Cancer Institute. C1 NSABP, Ctr Biostat, Pittsburgh, PA 15212 USA. Aultman Hosp, Canton, OH 44710 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Wickerham, DL (reprint author), NSABP, Ctr Biostat, 4 Allegheny Ctr,5th Floor, Pittsburgh, PA 15212 USA. EM larry.wickerham@nsabp.org FU NCI NIH HHS [U10CA-69974, U10CA-69651, U10CA-37377, U10CA-12027] NR 33 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD JUL PY 2006 VL 30 IS 7 BP 1138 EP 1146 DI 10.1007/s00268-005-0552-5 PG 9 WC Surgery SC Surgery GA 063VX UT WOS:000239049100002 PM 16794909 ER PT J AU Jatoi, I Proschan, MA AF Jatoi, Ismail Proschan, Michael A. TI Clinical trial results applied to management of the individual cancer patient SO WORLD JOURNAL OF SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; EARLY BREAST-CANCER; SUBGROUP ANALYSIS; TREAT AB The application of clinical trial results to the management of the individual cancer patient is not always straightforward. The results of a clinical trial indicate the "average" effect of an intervention, often expressed in terms of an absolute risk reduction, which is an estimate of the likelihood of benefit for a particular patient. However, within any clinical trial, there might be differences between groups of patients in underlying pathology, genetics, or biology, and some patients might benefit more from a new treatment than others. Thus, within a clinical trial, it might also be useful to group together patients with similar characteristics, and test for subgroup interaction. The test for interaction will indicate whether the magnitude of benefit differs from one prognostic subgroup to the next (a quantitative interaction). Much less common are qualitative interactions, in which a new treatment is beneficial in one subgroup but harmful in another. If the test for subgroup interaction is significant, then the effects of treatment may indeed differ between subgroups of patients, but this should be confirmed in other trials before a treatment is implemented in clinical practice. C1 Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Natl Naval Med Res Inst, Dept Surg, Bethesda, MD 20814 USA. NIAID, Biostat Branch, Bethesda, MD 20814 USA. RP Jatoi, I (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM ismail.jatoi@us.army.mil NR 20 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD JUL PY 2006 VL 30 IS 7 BP 1184 EP 1189 DI 10.1007/s00268-006-0073-x PG 6 WC Surgery SC Surgery GA 063VX UT WOS:000239049100008 PM 16794903 ER PT J AU Miyata, M Watase, H Hori, W Shimada, M Nagata, K Gonzalez, FJ Yamazoe, Y AF Miyata, M. Watase, H. Hori, W. Shimada, M. Nagata, K. Gonzalez, F. J. Yamazoe, Y. TI Role for enhanced faecal excretion of bile acid in hydroxysteroid sulfotransferase-mediated protection against lithocholic acid-induced liver toxicity SO XENOBIOTICA LA English DT Article DE hydroxysteroid sulfotransferase (Sult2a); farnesoid X receptor (FXR); pregnenolone 16 alpha-carbonitrile (PCN); sulfation; lithocholic acid; toxicity ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; BILIARY-EXCRETION; NUCLEAR RECEPTORS; GENE-EXPRESSION; HEALTHY MAN; RAT; PXR; DETOXIFICATION; MICE AB The efficient clearance of toxic bile acids such as lithocholic acid (LCA) requires drug-metabolizing enzymes. We therefore assessed the influence of pregnenolone 16 alpha- carbonitrile (PCN) treatment on LCA-induced hepatotoxicity and disposition of LCA metabolites using female farnesoid X receptor (FXR)-null and wild-type mice. Marked decreases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and hepatic tauroLCA (TLCA) concentrations were found in LCA- fed wild-type mice co-treated with PCN. Whereas induction of Cyp3a and hydroxysteroid sulfotransferase (Sult2a) proteins was observed in FXR-null and wild-type mice, clear increases in biliary 3 alpha- sulfated TLCA but not total 6 alpha-hydroxy LCA (taurohyodeoxycholic acid and hyodeoxycholic acid) were only observed in PCN-treated wild-type mice. Biliary 3 alpha- sulfated TLCA output rate was increased 7.2-fold, but accounts for only 4.2% of total bile acid output rate in LCA and PCN-co-treated wild-type mice. Total 3 alpha- sulfated LCA (LCA and TLCA) was, however, the most abundant bile acid component in faeces suggesting that efficient faecal excretion of biliary 3 alpha- sulfated TLCA through escape from enterohepatic circulation. FXR-null mice, which have constitutively high levels of the Sult2a protein, were fed a diet supplemented with 1% LCA and 0.4% dehydroepiandrosterone (DHEA), a typical Sult2a substrate/inhibitor. The faecal total 3 alpha- sulfated bile acid excretion was reduced to 62% of FXR-null mice fed only the LCA diet. Hepatic TLCA concentration and serum AST activity were significantly higher in FXR-null mice fed DHEA and LCA diet than in FXR-null mice fed the LCA diet or DHEA diet. These results suggest that hepatic formation of 3 alpha- sulfated TLCA is a crucial factor for protection against LCA- induced hepatotoxicity. C1 Tohoku Univ, Div Drug Metab & Mol Toxicol, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Tohoku Univ, 21st Century COE Program Comprehens Res & Educ, Ctr Planning Drug Dev & Clin Evaluat, Sendai, Miyagi, Japan. RP Miyata, M (reprint author), Tohoku Univ, Div Drug Metab & Mol Toxicol, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan. EM miyata@mail.pharm.tohoku.ac.jp NR 37 TC 18 Z9 18 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUL PY 2006 VL 36 IS 7 BP 631 EP 644 DI 10.1080/00498250600776827 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 080ZF UT WOS:000240286300005 PM 16864508 ER PT J AU Briones, VR Chen, SY Riegel, AT Lechleider, RJ AF Briones, VR Chen, SY Riegel, AT Lechleider, RJ TI Mechanism of fibroblast growth factor-binding protein 1 repression by TGF-beta SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE fibroblast growth factor-binding protein 1; transforming growth factor-beta; Smad; transcriptional regulation; signal transduction ID FGF-BP; SMOOTH-MUSCLE; TRANSCRIPTIONAL COREPRESSOR; EXPRESSION PATTERN; ANGIOGENESIS; CTBP; CELL; DIFFERENTIATION; PROLIFERATION; RECRUITMENT AB Transforming growth factor-beta (TGF-beta) is the prototypical member of a family of growth factors that play important roles in normal development and human diseases. We identified the gene for fibroblast growth factor-binding protein 1 (FGF-BP1) as being significantly repressed following TGF-beta treatment. FGF-BP1 is an extracellular matrix bound protein that enhances fibroblast growth factor (FGF) signaling. We demonstrate here that TGF-beta signaling significantly represses FGF-BP1 expression in mesenchymal and neural crest cells undergoing in vitro smooth muscle differentiation. Analysis of the downstream signaling pathways shows that Smad2/3 are crucial for efficient FGF-BP1 repression by TGF-beta. Furthermore, we identified a novel element in the region from -785 to -782 bp of the FGF-BP1 promoter. which represents a known binding site for Hypermethylation in Cancer-1 (Hic-1). necessary for repression of FGF-BP1 by TGF-beta. These data define the molecular mechanism of transcriptional repression of an important target of TGF-beta signaling during angiogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Interdisciplinary Program Tumor Biol, Washington, DC 20057 USA. RP Lechleider, RJ (reprint author), NCI, Med Oncol Res Unit, Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM lechleiderr@mail.nih.gov FU NHLBI NIH HHS [R01HL65681] NR 34 TC 17 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 30 PY 2006 VL 345 IS 2 BP 595 EP 601 DI 10.1016/j.bbrc.2006.04.052 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 049FO UT WOS:000238001600008 PM 16690027 ER PT J AU Eells, JB Misler, JA Nikodem, VM AF Eells, Jeffrey B. Misler, Jaime A. Nikodem, Vera M. TI Reduced tyrosine hydroxylase and GTP cyclohydrolase mRNA expression, tyrosine hydroxylase activity, and associated neurochemical alterations in Nurr1-null heterozygous mice SO BRAIN RESEARCH BULLETIN LA English DT Article DE tyrosine hydroxylase; GTP cyclohydrolase; dopamine synthesis; Nurr1; NR4A2 ID MIDBRAIN DOPAMINERGIC-NEURONS; ORPHAN NUCLEAR RECEPTOR; PARKINSONS-DISEASE; GENE-EXPRESSION; NGFI-B; TARGETED DISRUPTION; LOCOMOTOR-ACTIVITY; SUBSTANTIA-NIGRA; PROGENITOR CELLS; KNOCKOUT MICE AB The nuclear receptor Nurr1 is essential for the development of midbrain dopamine neurons and appears to be an important regulator of dopamine levels as adult Nurr1-null heterozygous (+/-) mice have reduced mesolimbic/mesocortical dopamine levels. The mechanism(s) through which reduced Nurr1 expression affects dopamine levels has not been determined. Quantitative real-time PCR revealed a significant reduction in tyrosine hydroxylase (TH) and GTP cyclohydrolase (GTPCH) mRNA in ventral midbrain of +/- mice as compared to wild-type mice (+/+). The effect on TH expression was only observed at birth, while reduced GTP cyclohydrolase was also observed in the adult ventral tegemental area. No differences in dopamine transporter, vesicular monoamine transporter, dopamine D2 receptor or aromatic amino acid decarboxylase were observed. Since TH and GTPCH are both involved in dopamine synthesis, regulation of in vivo TH activity was measured in these mice. In vivo TH activity was reduced in nucleus accumbens and striatum of the +/- mice (24.7% and 15.7% reduction, respectively). In the striatum, gamma-butyrolactone exacerbated differences on +/- striatal TH activity (29.8% reduction) while haloperidol equalized TH activity between the +/+ and +/-. TH activity in the nucleus accumbens was significantly reduced in all conditions measured. Furthermore, dopamine levels in the striatum of +/- mice were significantly reduced after inhibition of dopamine synthesis or after haloperidol treatment but not under basal conditions while dopamine levels in the nucleus accumbens were reduced under basal conditions. Based on these data the +/- genotype results in changes in gene expression and impairs dopamine synthesis which can affect the maintenance of dopamine levels, although with differential effects between mesolimbic/mesocortical and nigrostriatal dopamine neurons. Together, these data suggest that Nurr1 may function to modify TH and GTPCH expression and dopamine synthesis. Published by Elsevier Inc. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Eells, JB (reprint author), Mississippi State Univ, Coll Vet Med, Box 6100,MS 39762, Mississippi State, MS 39762 USA. EM eells@cvm.msstate.edu OI Eells, Jeffrey/0000-0002-6381-1666 FU Intramural NIH HHS NR 57 TC 15 Z9 15 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUN 30 PY 2006 VL 70 IS 2 BP 186 EP 195 DI 10.1016/j.brainresbull.2006.05.004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 061IV UT WOS:000238866200008 PM 16782508 ER PT J AU Chandra, D Bratton, SB Person, MD Tian, YA Martin, AG Ayres, M Fearnhead, HO Gandhi, V Tang, DG AF Chandra, Dhyan Bratton, Shawn B. Person, Maria D. Tian, Yanan Martin, Angel G. Ayres, Mary Fearnhead, Howard O. Gandhi, Varsha Tang, Dean G. TI Intracellular nucleotides act as critical prosurvival factors by binding to cyctochrome c and inhibiting apoptosome SO CELL LA English DT Article ID CYTOCHROME-C; RIBONUCLEOTIDE REDUCTASE; DEPENDENT FORMATION; CASPASE ACTIVATION; IONIC-STRENGTH; CELL-DEATH; APAF-1; DATP; PROCASPASE-9; REQUIREMENT AB Cytochromec(CC)-initiated Apaf-1 apoptosome formation represents a key initiating event in apoptosis. This process can be reconstituted in vitro with the addition of CC and ATP or dATP to cell lysates. How physiological levels of nucleotides, normally at high mM concentrations, affect apoptosome activation remains unclear. Here we show that physiological levels of nucleotides inhibit the CC-initiated apoptosome formation and caspase-9 activation by directly binding to CC on several key lysine residues and thus preventing CC interaction with Apaf-1. We show that in various apoptotic systems caspase activation is preceded or accompanied by decreases in overall intracellular NTP pools. Microinjection of nucleotides inhibits whereas experimentally reducing NTP pools enhances both CC and apoptotic stimuli-induced cell death. Our results thus suggest that the intracellular nucleotides represent critical prosurvival factors by functioning as natural inhibitors of apoptosome formation and a barrier that cells must overcome the nucleotide barrier to undergo apoptosis cell death. C1 Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Smithville, TX 78957 USA. Univ Texas, Coll Pharm, Div Pharmacol & Toxicol, Austin, TX 78712 USA. Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA. NCI, Apoptosis Sect, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Univ Texas, MD Anderson Canc Ctr, Program Mol Carcinogenesis, Grad Sch Biomed Sci, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. RP Chandra, D (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Sci Pk, Smithville, TX 78957 USA. EM dhchandra@mdanderson.org; dtang@mdanderson.org RI Fearnhead, Howard/D-4826-2012 FU NCI NIH HHS [CA57629, CA90297]; NIA NIH HHS [AG023374]; NIEHS NIH HHS [ES009859, ES07784] NR 36 TC 76 Z9 77 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 30 PY 2006 VL 125 IS 7 BP 1333 EP 1346 DI 10.1016/j.cell.2006.05.026 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064QP UT WOS:000239104500016 PM 16814719 ER PT J AU Sharov, AA Dudekula, DB Ko, ISH AF Sharov, Alexei A. Dudekula, Dawood B. Ko, Minoru S. H. TI CisView: A browser and database of cis-regulatory modules predicted in the mouse genome SO DNA RESEARCH LA English DT Article DE transcription factor binding site; evolutionary conservation; promoter; enhancer; CpG island; transcription start site ID FACTOR-BINDING SITES; TRANSCRIPTION START SITES; GENE-EXPRESSION; WIDE ANALYSIS; UPSTREAM ENHANCER; STEM-CELLS; COMPUTATIONAL DETECTION; TISSUE-SPECIFICITY; PROMOTER ELEMENTS; CONTROL REGION AB To facilitate the analysis of gene regulatory regions of the mouse genome, we developed a CisView (http:// lgsun.grc.nia.nih.gov/cisview), a browser and database of genome-wide potential transcription factor binding sites (TFBSs) that were identified using 134 position-weight matrices and 219 sequence patterns from various sources and were presented with the information about sequence conservation, neighboring genes and their structures, GO annotations, protein domains, DNA repeats and CpG islands. Analysis of the distribution of TFBSs revealed that many TFBSs (N = 145) were over-represented near transcription start sites. We also identified potential cis-regulatory modules (CRMs) defined as clusters of conserved TFBSs in the entire mouse genome. Out of 739 074 CRMs, 157 442 had a significantly higher regulatory potential score than semi-random sequences generated with a 3rd-order Markov process. The CisView browser provides a user-friendly computer environment for studying transcription regulation on a whole-genome scale and can also be used for interpreting microarray experiments and identifying putative targets of transcription factors. C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, ISH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009; OI Ko, Minoru/0000-0002-3530-3015; Dudekula, Dawood/0000-0002-4054-1827 FU Intramural NIH HHS NR 88 TC 19 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1340-2838 EI 1756-1663 J9 DNA RES JI DNA Res. PD JUN 30 PY 2006 VL 13 IS 3 BP 123 EP 134 DI 10.1093/dnares/dsl005 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 103UV UT WOS:000241913100004 PM 16980320 ER PT J AU Eun, SY Kim, EH Kang, KS Kim, HJ Jo, SA Kim, SJ Jo, SH Kim, SJ Blackshear, PJ Kim, J AF Eun, Su-Yong Kim, Eun Hae Kang, Kee-Seok Kim, Hwa Jung Jo, Sangmee Ahn Kim, Soon-Jong Jo, Su-Hyun Kim, Sang Jeong Blackshear, Perry J. Kim, Jun TI Cell type-specific upregulation of myristoylated alanine-rich C kinase substrate and protein kinase C-alpha, -beta I -beta II, and -delta in microglia following kainic acid-induced seizures SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE gene expression; kainic acid; microglia; myristoylated alanine-rich C kinase substrate; protein kinase C; seizures ID MARCKS PROTEIN; MUTANT MICE; HIPPOCAMPUS; EXPRESSION; FAMILY; LIPOPOLYSACCHARIDE; PHOSPHORYLATION; TRANSLOCATION; FIBROBLASTS; ACTIVATION AB Myristoylated alanine-rich C kinase substrate (MARCKS) is a widely distributed protein kinase C (PKC) substrate and has been implicated in actin cytoskeletal rearrangement in response to extracellular stimuli. Although MARCKS was extensively examined in various cell culture systems, the physiological function of MARCKS in the central nervous system has not been clearly understood. We investigated alterations of cellular distribution and phosphorylation of MARCKS in the hippocampus following kainic acid (KA)-induced seizures. KA (25 mg/kg, i.p.) was administered to eight to nine week-old C57BL/6 mice. Behavioral seizure activity was observed for 2 h after the onset of seizures and was terminated with diazepam (8 mg/kg, i.p.). The animals were sacrificed and analyzed at various points in time after the initiation of seizure activity. Using double-labeling immunofluorescence analysis, we demonstrated that the expression and phosphorylation of MARCKS was dramatically upregulated specifically in microglial cells after KA-induced seizures, but not in other types of glial cells. PKC alpha, beta I, beta II and delta, from various PKC isoforms examined, also were markedly upregulated, specifically in microglial cells. Moreover, immunoreactivities of phosphorylated MARCKS were colocalized in the activated microglia with those of the above isoforms of PKC. Taken together, our in vivo data suggest that MARCKS is closely linked to microglial activation processes, which are important in pathological conditions, such as neuroinflammation and neurodegeneration. C1 Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul 110799, South Korea. Cheju Natl Univ, Coll Med, Dept Physiol, Cheju 690756, South Korea. Natl Inst Hlth, Dept Biomed Sci, Seoul 122701, South Korea. Natl Inst Hlth, Biomed Brain Res Ctr, Seoul 122701, South Korea. Mokpo Natl Univ, Dept Chem, Choongnam 534729, South Korea. Natl Inst Environm Hlth Sci, Off Clin Res, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Kim, SJ (reprint author), Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul 110799, South Korea. EM kimjun@plaza.snu.ac.kr RI Kim, Sang Jeong/J-2740-2012; Kim, Jun/J-5432-2012 NR 28 TC 7 Z9 8 U1 0 U2 1 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD JUN 30 PY 2006 VL 38 IS 3 BP 310 EP 319 PG 10 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 062DT UT WOS:000238925500015 PM 16819290 ER PT J AU McCauslin, CS Heath, V Colangelo, AM Malik, R Lee, S Mallei, A Mocchetti, I Johnson, PF AF McCauslin, CS Heath, V Colangelo, AM Malik, R Lee, S Mallei, A Mocchetti, I Johnson, PF TI CAAT/enhancer-binding protein delta and cAMP-response element-binding protein mediate inducible expression of the nerve growth factor gene in the central nervous system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C6-2B GLIOMA-CELLS; C/EBP-BETA; RAT HIPPOCAMPUS; TRANSCRIPTION FACTORS; FACTOR BIOSYNTHESIS; MESSENGER-RNA; IN-VITRO; AGONIST CLENBUTEROL; ALZHEIMERS-DISEASE; ISCHEMIC DAMAGE AB Nerve growth factor (NGF) synthesis in the rat cerebral cortex is induced by the beta 2-adrenergic receptor agonist clenbuterol (CLE). Because NGF is a crucial neurotrophic factor for basal forebrain cholinergic neurons, defining the mechanisms that regulate its transcription is important for developing therapeutic strategies to treat pathologies of these neurons. We previously showed that the transcription factor CCAAT/enhancer-binding protein delta(C/EBP delta) contributes to NGF gene regulation. Here we have further defined the function of C/EBP delta and identified a role for cAMP response element- binding protein ( CREB) in NGF transcription. Inhibition of protein kinase A in C6-2B glioma cells suppressed CLE induction of an NGF promoter-reporter construct, whereas overexpression of protein kinase A increased NGF promoter activity, particularly in combination with C/EBP delta. A CRE-like site that binds CREB was identified in the proximal NGF promoter, and C/EBP delta and CREB were found to associate with the NGF promoter in vivo. Deletion of the CRE and/or C/EBP sites reduced CLE responsiveness of the promoter. In addition, ectopic expression of C/EBP delta in combination with CLE treatment increased endogenous NGF mRNA levels in C6-2B cells. C/EBP delta null mice showed complete loss of NGF induction in the cerebral cortex following CLE treatment, demonstrating a critical role for C/EBP delta in regulating beta 2-adrenergic receptor-mediated NGF expression in vivo. Thus, our findings demonstrate a critical role for C/EBP delta in regional expression of NGF in the brain and implicate CREB in CLE-induced NGF gene transcription. C1 NCI, Lab Prot Dynam & Signaling, NIH, Ft Detrick, MD 21702 USA. Georgetown Univ, Ctr Med, Dept Neurosci, Washington, DC 20057 USA. RP Johnson, PF (reprint author), NCI, Lab Prot Dynam & Signaling, NIH, Bldg 539,Rm 122,POB B, Ft Detrick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012; Malik, Radek/G-3578-2014 OI Johnson, Peter/0000-0002-4145-4725; FU Intramural NIH HHS; NINDS NIH HHS [NS 29664] NR 54 TC 28 Z9 31 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 30 PY 2006 VL 281 IS 26 BP 17681 EP 17688 DI 10.1074/jbc.M600207200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 055ZO UT WOS:000238490300017 PM 16632469 ER PT J AU Pikis, A Hess, S Arnold, I Erni, B Thompson, J AF Pikis, Andreas Hess, Sonja Arnold, Ingrid Erni, Bernhard Thompson, John TI Genetic requirements for growth of Escherichia coli K12 on methyl-alpha-D-glucopyranoside and the five alpha-D-glucosyl-D-fructose isomers of sucrose SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PHOSPHOTRANSFERASE SYSTEM; THERMOTOGA-MARITIMA; BACILLUS-SUBTILIS; FAMILY 4; FUSOBACTERIUM-MORTIFERUM; KLEBSIELLA-PNEUMONIAE; COLI K-12; BACTERIAL PHOSPHOENOLPYRUVATE; CARBOHYDRATE TRANSPORTERS; ENZYMES-II AB Strains of Escherichia coli K12, including MG-1655, accumulate methyl-alpha-D-glucopyranoside via the phosphoenolpyruvate-dependent glucose: phosphotransferase system (IICBGlc/IIA(Glc)). High concentrations of intracellular methyl-alpha-D-glucopyranoside 6-phosphate are toxic, and cell growth is prevented. However, transformation of E. coli MG-1655 with a plasmid (pAP1) encoding the gene aglB from Klebsiella pneumoniae resulted in excellent growth of the transformant MG-1655 (pAP1) on the glucose analog. AglB is an unusual NAD(+)/Mn2+-dependent phospho-alpha-glucosidase that promotes growth of MG-1655 (pAP1) by catalyzing the in vivo hydrolysis of methyl-alpha-D-glucopyranoside 6-phosphate to yield glucose 6-phosphate and methanol. When transformed with plasmid pAP2 encoding the K. pneumoniae genes aglB and aglA (an alpha-glucoside-specific transporter AglA (IICBAgl)), strain MG-1655 (pAP2) metabolized a variety of other alpha-linked glucosides, including maltitol, isomaltose, and the following five isomers of sucrose: trehalulose alpha(1 -> 1), turanose alpha(1 -> 3), maltulose alpha(1 -> 4), leucrose alpha(1 -> 5), and palatinose alpha(1 -> 6). Remarkably, MG-1655 (pAP2) failed to metabolize sucrose alpha(1 -> 2). The E. coli K12 strain ZSC112L (ptsG:: cat manXYZ nagE glk lac) can neither grow on glucose nor transport methyl-alpha-D-glucopyranoside. However, when transformed with pTSGH11 (encoding ptsG) or pAP2, this organism provided membranes that contained either the PtsG or AglA transporters, respectively. In vitro complementation of transporter-specific membranes with purified general phosphotransferase components showed that although PtsG and AglA recognized glucose and methyl-alpha-D-glucopyranoside, only AglA accepted other alpha-D-glucosides as substrates. Complementation experiments also revealed that IIA(Glc) was required for functional activity of both PtsG and AglA transporters. We conclude that AglA, AglB, and IIAGlc are necessary and sufficient for growth of E. coli K12 on methyl-alpha-D-glucoside and related alpha-D-glucopyranosides. C1 NIDCR, NIH, Dept Hlth & Human Serv, Microbial Biochem & Genet Unit,Oral Infect & Immu, Bethesda, MD 20892 USA. NIDDK, Proteom & Mass Spectrometry Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland. RP Thompson, J (reprint author), NIDCR, NIH, Dept Hlth & Human Serv, Microbial Biochem & Genet Unit,Oral Infect & Immu, Bldg 30,Rm 325,Convent Dr MSC-4350, Bethesda, MD 20892 USA. EM jthompson@dir.nidcr.nih.gov RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU Intramural NIH HHS NR 45 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 30 PY 2006 VL 281 IS 26 BP 17900 EP 17908 DI 10.1074/jbc.M601183200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 055ZO UT WOS:000238490300040 PM 16636060 ER PT J AU Preston, A Petersen, BO Duus, JO Kubler-Kielb, J Ben-Menachem, G Li, JJ Vinogradov, E AF Preston, Andrew Petersen, Bent O. Duus, Jens O. Kubler-Kielb, Joanna Ben-Menachem, Gil Li, Jianjun Vinogradov, Evgeny TI Complete structures of Bordetella bronchiseptica and Bordetella parapertussis lipopolysaccharides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPIRATORY-TRACT INFECTION; BIOSYNTHESIS LOCUS; O-ANTIGEN; PERTUSSIS; POLYSACCHARIDES; HOST; WLB AB The structures of the lipopolysaccharide (LPS) core and O antigen of Bordetella bronchiseptica and Bordetella parapertussis are known, but how these two regions are linked to each other had not been determined. We have studied LPS from several strains of these microorganisms to determine the complete carbohydrate structure of the LPS. LPS was analyzed using different chemical degradations, NMR spectroscopy, and mass spectrometry. This identified a novel pentasaccharide fragment that links the O chain to the core in all the LPS studied. In addition, although the O chain of these bacteria was reported as a homopolymer of 1,4-linked 2,3-diacetamido-2,3-dideoxy-alpha-galacturonic acid, we discovered that the polymer contains several amidated uronic acids, the number of which varies between strains. These new data describe the complete structure of the LPS carbohydrate backbone for both Bordetella species and help to explain the complex genetics of LPS biosynthesis in these bacteria. C1 Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. Carlsberg Lab, DK-2500 Copenhagen, Denmark. NICHD, NIH, Bethesda, MD 20892 USA. RP Vinogradov, E (reprint author), Natl Res Council Canada, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada. EM evguenii.vinogradov@nrc-cnrc.gc.ca RI Duus, Jens/N-4279-2013; OI Duus, Jens/0000-0003-3625-1250; Vinogradov, Evgeny/0000-0002-5364-1376 NR 25 TC 39 Z9 40 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 30 PY 2006 VL 281 IS 26 BP 18135 EP 18144 DI 10.1074/jbc.M513904200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 055ZO UT WOS:000238490300065 PM 16632471 ER PT J AU Matsumoto, K Kamiya, N Suwan, K Atsumi, F Shimizu, K Shinomura, T Yamada, Y Kimata, K Watanabe, H AF Matsumoto, K Kamiya, N Suwan, K Atsumi, F Shimizu, K Shinomura, T Yamada, Y Kimata, K Watanabe, H TI Identification and characterization of versican/PG-M aggregates in cartilage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHONDROITIN SULFATE PROTEOGLYCAN; HUMAN ARTICULAR-CARTILAGE; GROWTH-FACTOR; PG-M; PERICELLULAR MATRIX; LECTIN DOMAINS; LINK PROTEIN; LIMB BUD; IN-VIVO; AGGRECAN AB Versican/PG-M is a large chondroitin sulfate proteoglycan of the extracellular matrix with a common domain structure to aggrecan and is present in cartilage at low levels. Here, we characterized cartilage versican during development and growth. Immunostaining showed that versican was mainly localized in the interterritorial zone of the articular surface at 2 weeks in mice, whereas aggrecan was in the pericellular zone of prehypertrophic and hypertrophic cells of the growth plate. Although its transcription level rapidly diminished during growth, versican remained in the articular cartilage. Biochemical analysis of normal articular cartilage and aggrecan-null cartilage from cmd (cartilage matrix deficiency)/cmd mice revealed that versican was present as a proteoglycan aggregate with both link protein and hyaluronan. Chondroitin sulfate chains of versican digested with chondroitinase ABC contained 71% nonsulfated and 28% 4-sulfated unsaturated disaccharides, whereas those of aggrecan contained 25% nonsulfated and 70% 4-sulfated. Link protein overexpression in chondrocytic N1511 cells at the early stage of differentiation, in which versican is expressed, enhanced versican deposition in the matrix and prevented subsequent aggrecan deposition. These results suggest that versican is present as an aggregate distinct from the aggrecan aggregate and may play specific roles in the articular surface. C1 Aichi Med Univ, Inst Mol Sci Med, Nagakute, Aichi 4801195, Japan. Gifu Univ, Sch Med, Dept Orthopaed Surg, Gifu 5008705, Japan. Tokyo Med & Dent Univ, Dept Hard Tissue Engn, Tokyo 1138549, Japan. NIDCR, Craniofacial & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Watanabe, H (reprint author), Aichi Med Univ, Inst Mol Sci Med, Karimata 21, Nagakute, Aichi 4801195, Japan. EM wannabee@aichi-med-u.ac.jp NR 35 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 30 PY 2006 VL 281 IS 26 BP 18257 EP 18263 DI 10.1074/jbc.M510330200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 055ZO UT WOS:000238490300078 PM 16648631 ER PT J AU Perfetto, SP Chattopadhyay, PK Lamoreaux, L Nguyen, R Ambrozak, D Koup, RA Roederer, M AF Perfetto, Stephen P. Chattopadhyay, Pratip K. Lamoreaux, Laurie Nguyen, Richard Ambrozak, David Koup, Richard A. Roederer, Mario TI Amine reactive dyes: An effective tool to discriminate live and dead cells in polychromatic flow cytometry SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE amine reactive dye; cell viability; non-specific MAB-conjugate binding ID VIABILITY; POPULATIONS AB Membrane-damaged cells caused by either mechanical trauma or through normal biological processes can produce artifacts in immunophenotyping analysis by flow cytometry. Dead cells can nonspecifically bind monoclonal antibody conjugates, potentially leading to erroneous conclusions, particularly when cell frequencies are low. To date, DNA intercalating dyes (Ethidium monoazaide (EMA), Propidium Iodide, 7AAD, etc.) or Annexin V have been commonly used to exclude dead cells; however, each suffer from technical problems. The first issue with such dyes is the dependence on a consistent dead cell source for fluorescence compensation. Another major issue is the stability of the staining; except for EMA, fixation and permeablization used for intracellular staining procedures can cause loss of fluorescence. EMA requires a UV exposure to covalently bond to DNA; while this dye is effective and is not affected by intracellular treatments it is weakly fluorescent. Here we report on the optimization of a new class of viability dyes, the amine reactive viability dyes (ViD) as a dead cell exclusion marker. The inclusion of ViD into the staining panel was found to be simple, reproducible and can have a significant benefit on the accuracy of identifying appropriate cell populations. We show the fluorescence of cells stained with these dyes correlates with traditional dead cell discriminating markers, even after fixation and permeabilization. Amine reactive viability dyes are a powerful tool for fluorescence immunophenotyping experiments. Published by Elsevier B.V. C1 NIAID, Vaccine Res Ctr, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, Immunol Lab, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov RI Chattopadhyay, Pratip/B-9227-2008; Roederer, Mario/G-1887-2011; OI Chattopadhyay, Pratip/0000-0002-5457-9666 FU Intramural NIH HHS [Z99 AI999999] NR 10 TC 125 Z9 127 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 30 PY 2006 VL 313 IS 1-2 BP 199 EP 208 DI 10.1016/j.jim.2006.04.007 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 067HM UT WOS:000239292500021 PM 16756987 ER PT J AU Garcia-Pineres, AJ Hildesheim, A Williams, M Trivett, M Strobl, S Pinto, LA AF Garcia-Pineres, Alfonso J. Hildesheim, Allan Williams, Marcus Trivett, Matthew Strobl, Susan Pinto, Ligia A. TI DNAse treatment following thawing of Cryopreserved PBMC is a procedure suitable for lymphocyte functional studies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE DNAse; PBMC; cytokine; proliferation; flow cytometry ID RECOMBINANT HUMAN DEOXYRIBONUCLEASE; BLOOD AB Testing freshly isolated PBMC is not practical for immune monitoring analysis in large clinical trials or natural history studies. Thus, cryopreserved PBMC represent a more practical alternative. However, cell clumping is a common problem following thawing of PBMC isolated from blood that was previously transported and stored. Cell clumping leads to loss of cells, and could affect cell function and/or phenotype. The development and validation of procedures that prevent cell clumping and preserve cell function and surface marker expression levels are necessary to allow evaluation of immune function and phenotype in cryopreserved samples from clinical studies. The incorporation of a DNAse treatment step in the standard thawing procedure efficiently avoided clump formation, and did not result in detectable changes in cell viability, expression of standard leukocyte surface markers or two key parameters of immune function, proliferation and cytokine induction in response to a variety of common stimuli. Therefore, this procedure seems suitable for standard immunologic assays. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Lab Cell Mediated Immun, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Pinto, LA (reprint author), NCI, HPV Immunol Lab, SAIC Frederick Inc, Bldg 469,Room 120, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 6 TC 7 Z9 8 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 30 PY 2006 VL 313 IS 1-2 BP 209 EP 213 DI 10.1016/j.jim.2006.04.004 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 067HM UT WOS:000239292500022 PM 16737707 ER PT J AU Balaji, S Iyer, LM Aravind, L Babu, MM AF Balaji, S. Iyer, Lakshminarayan M. Aravind, L. Babu, M. Madan TI Uncovering a hidden distributed architecture behind scale-free transcriptional regulatory networks SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcriptional network; co-regulation network; distributed robustness; scale-free structure; evolution ID SACCHAROMYCES-CEREVISIAE GENOME; ESCHERICHIA-COLI; CAENORHABDITIS-ELEGANS; ADAPTIVE EVOLUTION; GENETIC REDUNDANCY; METABOLIC NETWORK; COMPLEX NETWORKS; DUPLICATE GENES; YEAST; ROBUSTNESS AB Numerous studies in both prokaryotes and eukaryotes have shown that, under standard growth conditions, less than 20% of the protein-coding genes are essential for survival. This suggests that biological systems have evolved to have a high degree of robustness to mutational disruptions that can affect the majority of their genes. This mutational robustness could arise either due to redundancy, i.e. direct backup, or due to distributed architecture, i.e. indirect backup where multiple genes contribute to the functioning of a process in the system. Despite clear evidence for direct backup, the prevalence of indirect backup is poorly understood. In this study, we reveal the existence of a hidden distributed architecture behind the scale-free transcriptional regulatory network of yeast by applying a unique network transformation procedure and show that the network is tolerant even to mutations that disrupt regulatory hubs. Contrary to what is generally accepted, our observation that hubs can be lost or replaced in evolution suggests that this hidden distributed architecture behind scale-free networks protects the overall transcriptional program of the organism from mutations affecting major regulatory hubs. We show that the distributed architecture has been provided by an unexpectedly large number of coordinating partners for any regulatory protein. On the basis of these findings, we propose that the existence of such architecture can allow organisms to explore the adaptive landscape in changing environments by providing the plasticity required to reprogram levels of expression of specific genes that may enhance survival. Thus, an "over-engineered" backup system in the form of distributed architecture is likely to be a major determinant of the "evolvability" of the gene expression in organisms faced with environmental diversity. Published by Elsevier Ltd. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov; madanm@ncbi.nlm.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 44 TC 45 Z9 47 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 30 PY 2006 VL 360 IS 1 BP 204 EP 212 DI 10.1016/j.jmb.2006.04.026 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061AV UT WOS:000238844500019 PM 16730024 ER PT J AU Balaji, S Babu, MM Iyer, LM Luscombe, NM Aravind, L AF Balaji, S. Babu, M. Madan Iyer, Lakshminarayan M. Luscombe, Nicholas M. Aravind, L. TI Comprehensive analysis of combinatorial regulation using the transcriptional regulatory network of yeast SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcriptional network; co-regulation network; ubiquitin pathway; signal transduction; evolution ID SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; GENE-EXPRESSION; HYPOXIC GENES; PROTEIN; BINDING; PROTEASOME; UBIQUITIN; REPRESSION; EVOLUTION AB Studies on various model systems have shown that a relatively small number of transcription factors can set up strikingly complex spatial and temporal patterns of gene expression. This is achieved mainly by means of combinatorial or differential Gene regulation, i.e. regulation of a gene by two or more transcription factors simultaneously or under different conditions. While a number of specific molecular details of the mechanisms of combinatorial regulation have emerged, our understanding of the general principles of combinatorial regulation on a genomic scale is still limited. In this work, we approach this problem by using the largest assembled transcriptional regulatory network for yeast. A specific network transformation procedure was used to obtain the co-regulatory network describing the set of all significant associations among transcription factors in regulating con-m-ion target genes. Analysis of the global properties of the co-regulatory network suggested the presence of two classes of regulatory hubs: (i) those that make many co-regulatory associations, thus serving as integrators of disparate cellular processes; and (ii) those that make few coregulatory associations, and thereby specifically regulate one or a few major cellular processes. Investigation of the local structure of the co-regulatory network revealed a significantly higher than expected modular organization, which might have emerged as a result of selection by functional constraints. These constraints probably emerge from the need for extensive modular backup and the requirement to integrate transcriptional inputs of multiple distinct functional systems, We then explored the transcriptional control of three major regulatory systems (ubiquitin signaling, protein kinase and transcriptional regulation systems) to understand specific aspects of their upstream control. As a result, we observed that ubiquitin E3 ligases are regulated primarily by unique transcription factors, whereas E1 and E2 enzymes share common transcription factors to a much greater extent. This suggested that the deployment of E3s unique to specific functional contexts may be mediated significantly at the transcriptional level. Likewise, we were able to uncover evidence for much higher upstream transcription control of transcription factors themselves, in comparison to components of other regulatory systems. We believe that the results presented here might provide a framework for testing the role of co-regulatory associations in eukaryotic transcriptional control. Published by Elsevier Ltd. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. RP Balaji, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM sbalaji@ncbi.nlm.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 59 TC 127 Z9 130 U1 0 U2 12 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 30 PY 2006 VL 360 IS 1 BP 213 EP 227 DI 10.1016/j.jmb.2006.04.029 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061AV UT WOS:000238844500020 PM 16762362 ER PT J AU Marenco, S Rawlings, R Rohde, GK Barnett, AS Hone, RA Pierpaoli, C Weinberger, DR AF Marenco, Stefano Rawlings, Robert Rohde, Gustavo K. Barnett, Alan S. Hone, Robyn A. Pierpaoli, Carlo Weinberger, Daniel R. TI Regional distribution of measurement error in diffusion tensor imaging SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE reproducibility; statistical analysis; fractional anisotropy; mean diffusivity; magnetic resonance imaging ID WHITE-MATTER; MRI; SCHIZOPHRENIA; ANISOTROPY; DTI AB The characterization of measurement error is critical in assessing the significance of diffusion tensor imaging (DTI) findings in longitudinal and cohort studies of psychiatric disorders. We studied 20 healthy volunteers, each one scanned twice (average interval between scans of 51 +/- 46.8 days) with a single shot echo planar DTI technique. Intersession variability for fractional anisotropy (FA) and Trace (D) was represented as absolute variation (standard deviation within subjects: SDw), percent coefficient of variation (CV) and intraclass correlation coefficient (ICC). The values from the two sessions were compared for statistical significance with repeated measures analysis of variance or a non-parametric equivalent of a paired t-test. The results showed good reproducibility for both FA and Trace (CVs below 10% and ICCs at or above 0.70 in most regions of interest) and evidence of systematic global changes in Trace between scans. The regional distribution of reproducibility described here has implications for the interpretation of regional findings and for rigorous preprocessing. The regional distribution of reproducibility measures was different for SDw, CV and ICC. Each one of these measures reveals complementary information that needs to be taken into consideration when performing statistical operations on groups of DT images. Published by Elsevier Ireland Ltd. C1 NIMH, CBDB, Genes Cognit & Psychosis Program, IRP, Bethesda, MD 20892 USA. NIAAA, Sect Brain Electrophysiol & Imaging, LCS, IRP, Bethesda, MD USA. NICHD, Sect Tissue Biophys & Biomimet, LIMB, IRP, Bethesda, MD USA. RP Marenco, S (reprint author), NIMH, CBDB, Genes Cognit & Psychosis Program, IRP, 10 Ctr Dr,Bldg 10,Room 4S235, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011 OI Marenco, Stefano/0000-0002-2488-2365; FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002716-11] NR 18 TC 38 Z9 38 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUN 30 PY 2006 VL 147 IS 1 BP 69 EP 78 DI 10.1016/j.pscychresns.2006.01.008 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 076QW UT WOS:000239973800006 PM 16797169 ER PT J AU Pettigrew, RI AF Pettigrew, RI TI Team science and the NIBIB SO SCIENCE LA English DT Letter C1 Natl Inst Biomed Imaging & Bioengn, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pettigrew, RI (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 2006 VL 312 IS 5782 BP 1873 EP 1873 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061CF UT WOS:000238848100022 PM 16809509 ER PT J AU Moore, S Jaeschke, H Kleinau, G Neumann, S Costanzi, S Jiang, JK Childress, J Raaka, BM Colson, A Paschke, R Krause, G Thomas, CJ Gershengorn, MC AF Moore, Susanna Jaeschke, Holger Kleinau, Gunnar Neumann, Susanne Costanzi, Stefano Jiang, Jian-kang Childress, John Raaka, Bruce M. Colson, Anny Paschke, Ralf Krause, Gerd Thomas, Craig J. Gershengorn, Marvin C. TI Evaluation of small-molecule modulators of the luteinizing hormone/choriogonadotropin and thyroid stimulating hormone receptors: Structure-activity relationships and selective binding patterns SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID AGONISTS; IDENTIFICATION; ANTAGONISTS; LH AB The substituted thieno[ 2,3-d] pyrimidine 3 ( Org 41841), a partial agonist for the luteinizing hormone/choriogonadotropin receptor ( LHCGR) and the closely related thyroid-stimulating hormone receptor ( TSHR), was fundamentally altered, and the resulting analogues were analyzed for their potencies, efficacies, and specificities at LHCGR and TSHR. Chemical modification of the parent compound combined with prior mutagenesis of TSHR provided compelling experimental evidence in support of computational models of 3 binding to TSHR and LHCGR within their transmembrane cores. Biochemical analysis of a specific modification to the chemical structure of 3 provides additional evidence of a H-bond between the ligand and a glutamate residue in transmembrane helix 3, which is conserved in both receptors. Several key interactions were surveyed to determine their respective biochemical roles in terms of both van der Waals dimensions and hydrogen bond capacity and the respective relationship to biological activity. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. NIDDKD, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. Leibniz Inst Mol Pharmakol, D-13125 Berlin, Germany. RP Gershengorn, MC (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Costanzi, Stefano/G-8990-2013; OI Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK070005-04, Z01 DK011006-06, Z01 DK047045-01] NR 17 TC 45 Z9 49 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 29 PY 2006 VL 49 IS 13 BP 3888 EP 3896 DI 10.1021/jm060247s PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 055JN UT WOS:000238446700016 PM 16789744 ER PT J AU Romagnoli, R Baraldi, PG Pavani, MG Tabrizi, MA Preti, D Fruttarolo, F Piccagli, L Jung, MK Hamel, E Borgatti, M Gambari, R AF Romagnoli, Romeo Baraldi, Pier Giovanni Pavani, Maria Giovanna Tabrizi, Mojgan Aghazadeh Preti, Delia Fruttarolo, Francesca Piccagli, Laura Jung, M. Katherine Hamel, Ernest Borgatti, Monica Gambari, Roberto TI Synthesis and biological evaluation of 2-amino-3-(3 ',4 ',5 '-trimethoxybenzoyl)-5-aryl thiophenes as a new class of potent antitubulin agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIMITOTIC NATURAL-PRODUCTS; TUBULIN POLYMERIZATION; COMBRETASTATIN A-4; ANTINEOPLASTIC AGENTS; IN-VITRO; ANALOGS; DRUGS; DERIVATIVES; APOPTOSIS; CELLS AB A new series of compounds in which the 2-amino-5-chlorophenyl ring of phenstatin analogue 7 was replaced with a 2-amino-5-aryl thiophene was synthesized and evaluated for antiproliferative activity and for inhibition of tubulin polymerization and colchicine binding to tubulin. 2-Amino-3-( 3', 4', 5'-trimethoxybenzoyl)-5-phenyl thiophene ( 9f) as well as the p-fluoro-, p-methyl-, and p-methoxyphenyl substituted analogues ( 9i, j, and l, respectively) displayed high antiproliferative activities with IC50 values from 2.5 to 6.5 nM against the L1210 and K562 cell lines. Compounds 9i and j were more active than combretastatin A-4 as inhibitors of tubulin polymerization. Molecular docking simulations to the colchicine site of tubulin were performed to determine the possible binding mode of 9i. The results obtained demonstrated that antiproliferative activity correlated well with the inhibition of tubulin polymerization and the lengthening of the G2/M phase of the cell cycle. Moreover, a good correlation was found between these inhibitory effects and the induction of apoptosis in cells treated with the compounds. C1 Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. Natl Canc Inst, NIH, Frederick, MD 21702 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Natl Inst Hlth, Frederick, MD 21702 USA. Univ Ferrara, Mol Biol Sect, Dipartimento Biochim & Biol Mol, I-44100 Ferrara, Italy. RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. EM rmr@unife.it; baraldi@unife.it RI Aghazadeh Tabrizi, Mojgan/I-9169-2014; Gambari, Roberto/F-9555-2015; Borgatti, Monica/G-2611-2015; preti, delia/G-9916-2015; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier Giovanni/B-7933-2017 OI Gambari, Roberto/0000-0001-9205-6033; Borgatti, Monica/0000-0001-8470-2496; preti, delia/0000-0002-1075-3781; FU NCI NIH HHS [N0-CO-12400] NR 47 TC 55 Z9 55 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 29 PY 2006 VL 49 IS 13 BP 3906 EP 3915 DI 10.1021/jm060355e PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 055JN UT WOS:000238446700018 PM 16789746 ER PT J AU Ballet, S Salvadori, S Trapella, C Bryant, SD Jinsmaa, Y Lazarus, LH Negri, L Giannini, E Lattanzi, R Tourwe, D Balboni, G AF Ballet, Steven Salvadori, Severo Trapella, Claudio Bryant, Sharon D. Jinsmaa, Yunden Lazarus, Lawrence H. Negri, Lucia Giannini, Elisa Lattanzi, Roberta Tourwe, Dirk Balboni, Gianfranco TI New 2 ',6 '-dimethyl-L-tyrosine (Dmt) opioid peptidomimetics based on the Aba-Gly scaffold. Development of unique mu-opioid receptor ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TIC PHARMACOPHORE; TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID; PEPTIDES; POTENT; ANALOGS; ANTAGONIST; AGONIST; SEQUENCE; MOTIF AB The Aba-Gly scaffold, incorporated into Dmt-Tic ligands ( H-Dmt-Tic-Gly-NH-CH2-Ph,H-Dmt-Tic-Gly-NH-Ph, H-Dmt-Tic-NH-CH2-Bid), exhibited mixed mu/delta or delta opioid receptor activities with A agonism. Substitution of Tic by Aba-Gly coupled to -NH-CH2-Ph ( 1), -NH-Ph ( 2), or -Bid ( Bid) 1H-benzimidazole-2-yl) ( 3) shifted affinity ( Ki( mu)) 0.46, 1.48, and 19.9 nM, respectively), selectivity, and bioactivity to mu-opioid receptors. These compounds represent templates for a new class of lead opioid agonists that are easily synthesized and suitable for therapeutic pain relief. C1 Free Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol Vittorio Erspamer, I-00185 Rome, Italy. RP Balboni, G (reprint author), Free Univ Brussels, Dept Organ Chem, Pleinlaan 2, B-1050 Brussels, Belgium. EM gbalboni@unica.it RI Trapella, Claudio/I-2128-2012; OI Trapella, Claudio/0000-0002-6666-143X; LATTANZI, Roberta/0000-0002-6377-9256 FU Intramural NIH HHS [Z01 ES090053-20, Z01 ES100472-06, Z99 ES999999] NR 23 TC 8 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 29 PY 2006 VL 49 IS 13 BP 3990 EP 3993 DI 10.1021/jm0603264 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 055JN UT WOS:000238446700028 PM 16789756 ER PT J AU Bower, JF Li, YX Wyatt, R Ross, TM AF Bower, JF Li, YX Wyatt, R Ross, TM TI HIV-1 Env(gp140) trimers elicit neutralizing antibodies without efficient induction of conformational antibodies SO VACCINE LA English DT Article; Proceedings Paper CT 2nd Immunopotentiators in Modern Vaccines Meeting (IMV-II) CY MAY 18-20, 2005 CL Malaga, SPAIN DE HIV-1; Env; antigenicity; immunogenicity; C3d; trimers; neutralization ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN TRIMERS; HUMAN MONOCLONAL-ANTIBODIES; NUCLEIC-ACID IMMUNIZATION; DNA VACCINES; TYPE-1 ENVELOPE; IMMUNE-RESPONSES; GP120 GLYCOPROTEIN; C3D ENHANCEMENT; FUSION PROTEINS AB Currently, no vaccine for human immunodeficiency virus (HIV-1) provides protection from virus infection. One reason for these disappointing results has been the difficulty of current vaccine candidates to elicit high-titer, broadly reactive immunity to a large number of viral proteins. Recently, our laboratory demonstrated that the coupling of CM to a soluble trimerized HIV-1 envelope (Env(gp140(FT))) elicited higher titers of neutralizing antibodies than monomers of Env(gp120) coupled to CM [Bower JF, Yang X, Sodroski J, Ross TM. Elicitation of neutralizing antibodies with DNA vaccines expressing soluble stabilized human immunodeficiency virus type 1 envelope glycoprotein trimers conjugated to C3d. J Virol 2004;78(9):4710-9]. To determine if the induction of conformational antibodies correlated with neutralization, mice (BALB/c) were primed (2x) with DNA plasmids expressing monomeric Env(gp120) or trimeric Env(gp140) alone or fused to mC3d(3) at one of two doses (2.0 mu g or 0.2 mu g), followed by a boost of recombinant uncleaved, trimeric Env(gp140). Regardless of the priming dose of DNA, all mice had high-titer anti-Env IgG antibodies. Interestingly, Env(gp140) trimers did not elicit higher titers of antibodies that recognized conformational Env epitopes compared to monomers of Env(gp120). Therefore, additional parameters were examined for correlation with neutralization. For neutralization-resistant HIV-1 isolates, ADA and YU-2, neutralization correlated with high-titer, high avidity antibodies, with Env(gp140) eliciting slightly higher neutralization titers than Env(gp120). In contrast, none of the measured parameters correlated with neutralization for the more neutralization-sensitive isolates, MN or 89.6. Therefore, even though soluble, uncleaved Envgp140 trimers may be marginally more effective at eliciting neutralizing antibodies than Env(gp120), neutralization does not appear to correlate with the elicitation of conformationally dependent antibodies. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA. NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Ross, TM (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Scaife Hall,Room S871,3550 Terrace St, Pittsburgh, PA 15261 USA. EM joseph.bower@sanofipasteur.com; rosst@dom.pitt.edu NR 82 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 29 PY 2006 VL 24 IS 26 BP 5442 EP 5451 DI 10.1016/j.vaccine.2006.03.063 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 058BI UT WOS:000238638700009 PM 16621193 ER PT J AU Chou, SP Dawson, DA Stinson, FS Huang, BJ Pickering, RP Zhou, Y Grant, BF AF Chou, SP Dawson, DA Stinson, FS Huang, BJ Pickering, RP Zhou, Y Grant, BF TI The prevalence of drinking and driving in the United States, 2001-2002: Results from the national epidemiological survey on alcohol and related conditions SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE prevalence; drinking and driving; sex differentials ID SENSATION SEEKING; AMERICAN-INDIANS; VEHICLE CRASHES; US ADULTS; DRUG-USE; RISK; POPULATION; BEHAVIORS; FATALITIES; STUDENTS AB Traffic deaths and injuries are among the most frequent causes of deaths and disability worldwide. In the United States, the National Highway Transportation Safety Administration (NHTSA) reported that approximately 40% of all traffic fatalities were alcohol-related. Yet, information about the prevalence of drinking and driving behaviors of the U.S. general population is lacking. The purpose of this study was to examine the magnitude of driver-based (i.e., driving while drinking and driving after having too much to drink) and passenger-based (i.e., riding with a drinking driver and riding as a passenger while drinking) drinking and driving behaviors confronting contemporary America. The past-year prevalence data were stratified by major sociodemographic characteristics to identify important determinants of drinking and driving behaviors for further research. Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n=43,093). In 2001-2002 there were 23.4 million, or 11.3%, of American adults who reported engaging in at least one of the four driver- or passenger-based drinking and driving behaviors. The prevalences of passenger-based drinking and driving behaviors were generally greater than those of the driver-based measures. For all four drinking and driving behaviors, age was inversely associated with the risk and males were at greater risk with the associated male-to-female ratios of approximately 3.0. Our data also suggested that Native Americans, individuals who were widowed/separated/divorced or never married, and those with greater than a high school education were also at greater risks of all drinking and driving behaviors. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Chou, SP (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3073,5635 Fishers Lane,MS 9304, Bethesda, MD 20892 USA. EM pchou@mail.nih.gov FU Intramural NIH HHS NR 57 TC 60 Z9 62 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 28 PY 2006 VL 83 IS 2 BP 137 EP 146 DI 10.1016/j.drugalcdep.2005.11.001 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 058ZC UT WOS:000238702100006 PM 16364565 ER PT J AU DiCicco-Bloom, E Lord, C Zwaigenbaum, L Courchesne, E Dager, SR Schmitz, C Schultz, RT Crawley, J Young, LJ AF DiCicco-Bloom, Emanuel Lord, Catherine Zwaigenbaum, Lonnie Courchesne, Eric Dager, Stephen R. Schmitz, Christoph Schultz, Robert T. Crawley, Jacqueline Young, Larry J. TI The developmental neurobiology of autism spectrum disorder SO JOURNAL OF NEUROSCIENCE LA English DT Review DE cerebellum; autism; behavior; cognitive; brain development; imaging; mice; fMRI; genetics; Purkinje neurons; human forebrain development; cerebral cortex ID FUSIFORM FACE AREA; CYCLASE-ACTIVATING POLYPEPTIDE; HOMEOBOX-TRANSCRIPTION-FACTOR; SOCIAL RECOGNITION; HEAD CIRCUMFERENCE; MENTAL-RETARDATION; BRAIN-DEVELOPMENT; CEREBRAL-CORTEX; SONIC HEDGEHOG; FRONTAL-CORTEX C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat Neurol, Piscataway, NJ 08854 USA. Univ Michigan, Autism & Commun Disorders Ctr, Dept Psychol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. McMaster Univ, Dept Pediat, Hamilton, ON L8N 3Z5, Canada. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Childrens Hosp, Res Ctr, Ctr Autism Res, San Diego, CA 92123 USA. Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Bioengn, Seattle, WA 98105 USA. Maastricht Univ, Dept Psychiat & Neuropsychol, Div Cellular Neurosci, NL-6200 MD Maastricht, Netherlands. Yale Univ, Yale Child Study Ctr & Diagnost Radiol, New Haven, CT 06520 USA. NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Ctr Behav Neurosci, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Sch Med, Dept Psychiat, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. RP DiCicco-Bloom, E (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, 675 Hoes Lane,RWJSPH Room 362, Piscataway, NJ 08854 USA. EM diciccem@umdnj.edu FU NICHD NIH HHS [HD23315]; NINDS NIH HHS [NS32401] NR 139 TC 191 Z9 198 U1 16 U2 40 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 28 PY 2006 VL 26 IS 26 BP 6897 EP 6906 DI 10.1523/JNEUROSCI.1712-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 060LT UT WOS:000238804400002 PM 16807320 ER PT J AU Nasu-Nishimura, Y Hurtado, D Braud, S Tang, TTT Isaac, JTR Roche, KW AF Nasu-Nishimura, Yukiko Hurtado, David Braud, Stephanie Tang, Tina Tze-Tsang Isaac, John T. R. Roche, Katherine W. TI Identification of an endoplasmic reticulum-retention motif in an intracellular loop of the kainate receptor subunit KA2 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GluR6; glutamate receptor; trafficking; ER-retention; oligomerization; surface expression ID SURFACE EXPRESSION; SPLICE VARIANTS; QUALITY-CONTROL; RAT-BRAIN; TRAFFICKING; SIGNAL; GLUR6; CHANNELS; COMPLEX; ROLES AB Neuronal kainate receptors are typically heteromeric complexes composed of GluR5-7 and KA1-2 subunits. Although GluR5-7 can exist as functional homomeric channels, the KA subunits cannot. KA2 is widely expressed in the CNS, and KA2/GluR6 heteromers are the most prevalent subunit composition in brain. Previous work has identified endoplasmic reticulum (ER)-retention motifs in the C terminus of KA2, which prevent surface expression of KA2 homomers. However, we find that, when these motifs are mutated, only a small fraction of KA2 is surface expressed. We now identify an additional ER retention motif in the intracellular loop region of KA2, which, when mutated together with the C-terminal motifs, significantly increases the level of KA2 surface expression. However, electrophysiological analysis of surface-expressed KA2 homomers indicates that they do not form functional ion channels. In heterologous cells, a large fraction of KA2 remains intracellular even when the trafficking motifs are mutated or when GluR6 is coexpressed. Therefore, we analyzed the trafficking of endogenous KA2 in vivo. We find that native KA2 surface expression is dramatically reduced in GluR6 knock-out mice compared with wild-type mice. In contrast, KA2 trafficking was unaffected in the GluR5 knock-out. Thus, our study demonstrates that trafficking motifs in both the intracellular loop and C terminus regulate KA2 surface expression; however, in neurons, GluR6 oligomerization is required for egress of KA2 from the ER and transport to the cell surface. The combination of these mechanisms likely prevents surface expression of nonfunctional KA2 homomers and ensures a high level of GluR6/KA2 heteromeric kainate receptors. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Bristol, Med Res Council Ctr Synapt Plast, Dept Anat, Bristol BS8 1TD, Avon, England. RP Roche, KW (reprint author), NINDS, NIH, Bldg 35,Room 2C903, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU Intramural NIH HHS; Wellcome Trust NR 23 TC 43 Z9 43 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 28 PY 2006 VL 26 IS 26 BP 7014 EP 7021 DI 10.1523/JNEUROSCI.0573-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 060LT UT WOS:000238804400015 PM 16807331 ER PT J AU Ahmed, ZM Goodyear, R Riazuddin, S Lagziel, A Legan, PK Behra, M Burgess, SM Lilley, KS Wilcox, ER Riazuddin, S Griffith, AJ Frolenkov, GI Belyantseva, IA Richardson, GP Friedman, TB AF Ahmed, Zubair M. Goodyear, Richard Riazuddin, Saima Lagziel, Ayala Legan, P. Kevin Behra, Martine Burgess, Shawn M. Lilley, Kathryn S. Wilcox, Edward R. Riazuddin, Sheikh Griffith, Andrew J. Frolenkov, Gregory I. Belyantseva, Inna A. Richardson, Guy P. Friedman, Thomas B. TI The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE protocadherin-15; tip link; TLA; stereocilia; mechanotransduction; hair cell ID AVIAN INNER-EAR; USHER-SYNDROME; MECHANICAL TRANSDUCTION; CALCIUM CHELATION; KINOCILIAL LINKS; PCDH15; BUNDLES; STEREOCILIA; CADHERIN-23; MUTATIONS AB Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formation. C1 Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England. Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Rockville, MD 20850 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Biochem, Cambridge Ctr Proteom, Cambridge CB2 1QW, England. Brigham Young Univ, DNA Sequencing Ctr, Dept Integrat Biol, Provo, UT 84602 USA. Natl Ctr Excellence Mol Biol, Lahore, Pakistan. Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA. RP Richardson, GP (reprint author), Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England. EM g.p.richardson@sussex.ac.uk; friedman@nidcd.nih.gov OI Burgess, Shawn/0000-0003-1147-0596; Frolenkov, Gregory/0000-0002-9810-5024 FU NIDCD NIH HHS [1 Z01 DC000039-09]; Wellcome Trust [071394/Z/03/Z] NR 36 TC 137 Z9 141 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 28 PY 2006 VL 26 IS 26 BP 7022 EP 7034 DI 10.1523/JNEUROSCI.1163-06.2006 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 060LT UT WOS:000238804400016 PM 16807332 ER PT J AU Gao, GH Prasad, R Lodwig, SN Unkefer, CJ Beard, WA Wilson, SH London, RE AF Gao, GH Prasad, R Lodwig, SN Unkefer, CJ Beard, WA Wilson, SH London, RE TI Determination of lysine pK values using [5-C-13]lysine: Application to the lyase domain of DNA pol beta SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PK(A) VALUES; POLYMERASE-BETA; ACTIVE-SITE; PROTEIN STABILITY; NMR DETERMINATION; MECHANISM; RESIDUES; ENZYME; LACTAMASES; EXCISION C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Los Alamos Natl Lab, Biosci Div, Natl Stable Isotope Resource, Los Alamos, NM 87544 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050147-13]; NIBIB NIH HHS [P41 EB002166-18, P41 EB002166, 5P41 EB002166] NR 20 TC 11 Z9 11 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 28 PY 2006 VL 128 IS 25 BP 8104 EP 8105 DI 10.1021/ja061473u PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 054ZM UT WOS:000238418000004 PM 16787052 ER PT J AU Jin, P Wang, E Provenzano, M Deola, S Selleri, S Ren, JQ Voiculescu, S Stroncek, D Panelli, MC Marincola, FM AF Jin, Ping Wang, Ena Provenzano, Maurizio Deola, Sara Selleri, Silvia Ren, Jiaqiang Voiculescu, Sonia Stroncek, David Panelli, Monica C. Marincola, Francesco M. TI Molecular signatures induced by interleukin-2 on peripheral blood mononuclear cells and T cell subsets SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID IMMUNE-RESPONSE MODIFIER; HIGH-DOSE INTERLEUKIN-2; HEPATITIS-C VIRUS; ALPHA CHAIN EXPRESSION; RECEPTOR-BETA CHAIN; REGULATORY FACTOR-I; GENE-EXPRESSION; TRANSFERRIN RECEPTOR; METASTATIC MELANOMA; IL-2 RECEPTOR AB Experimentally, interleukin-2 (IL-2) exerts complex immunological functions promoting the proliferation, survival and activation of T cells on one hand and inducing immune regulatory mechanisms on the other. This complexity results from a cross talk among immune cells which sways the effects of IL-2 according to the experimental or clinical condition tested. Recombinant IL-2 (rIL-2) stimulation of peripheral blood mononuclear cells (PBMC) from 47 donors of different genetic background induced generalized T cell activation and anti-apoptotic effects. Most effects were dependent upon interactions among immune cells. Specialized functions of CD4 and CD8 T cells were less dependent upon and often dampened by the presence of other PBMC populations. In particular, cytotoxic T cell effector function was variably affected with a component strictly dependent upon the direct stimulation of CD8 T cells in the absence of other PBMC. This observation may provide a roadmap for the interpretation of the discrepant biological activities of rIL-2 observed in distinct pathological conditions or treatment modalities. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Hosp ZLF, Dept Surg, Immune Oncol Sect, CH-4031 Basel, Switzerland. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM pjin@cc.nih.gov; ewang@cc.nih.gov; maurizio_provenzano@yahoo.it; sdeola@cc.nih.gov; selleris@cc.nih.gov; renj@cc.nih.gov; voiculescus@cc.nih.gov; Dstroncek@cc.nih.gov; MPanelli@mail.cc.nih.gov; FMarincola@cc.nih.gov NR 120 TC 25 Z9 27 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 28 PY 2006 VL 4 AR 26 DI 10.1186/1479-5876-4-26 PG 23 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 078ZK UT WOS:000240145100001 PM 16805915 ER PT J AU Jiang, GH Skorvaga, M Croteau, DL Van Houten, B States, JC AF Jiang, GH Skorvaga, M Croteau, DL Van Houten, B States, JC TI Robust incision of benoz[a]pyrene-7,8-dihyrodiol-9,10-epoxide-DNA adducts by a recombinant thermoresistant interspecies combination UvrABC endonuclease system SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; BENZOPYRENE DIOL EPOXIDE; DNA PREINCISION COMPLEX; C-TERMINAL REGION; THERMOTOGA-MARITIMA; UVRB PROTEIN; 2 FORMS; SEQUENCE; BINDING; DAMAGE AB Prokaryotic DNA repair nucleases are useful reagents for detecting DNA lesions. UvrABC endonuclease, encoded by the UvrA, UvrB, and UvrC genes can incise DNA containing bulky nucleotide adducts and intrastrand cross-links. UvrA, UvrB, and UvrC were cloned from Bacillus caldotenax (Bca) and UvrC from Thermatoga maritima (Tma), and recombinant proteins were overexpressed in and purified from Escherichia coli. Incision activities of UvrABC composed of all Bca-derived subunits (UvrABC(Bca)) and an interspecies combination UvrABC composed of Bca-derived UvrA and UvrB and Tma-derived UvrC (UvrABC(Tma)) were compared on benoz[a] pyrene-7,8-dihyrodiol-9,10-epoxide (BPDE)-adducted substrates. Both UvrABC(Bca) and UvrABC(Tma) specifically incised both BPDE-adducted plasmid DNAs and site-specifically modified 50-bp oligonucleotides containing a single (+)-trans- or (+)-cis-BPDE adduct. Incision activity was maximal at 55-60 degrees C. However, UvrABC(Tma) was more robust than UvrABC(Bca) with 4-fold greater incision activity on BPDE-adducted oligonucleotides and 1.5-fold greater on [H-3]BPDE-adducted plasmid DNAs. Remarkably, UvrABCBca incised only at the eighth phosphodiester bond 5' to the BPDE-modified guanosine. In contrast, UvrABC(Tma) performed dual incision, cutting at both the fifth phosphodiester bond 3' and eighth phosphodiester bond 5' from BPDE-modified guanosine. BPDE adduct stereochemistry influenced incision activity, and cis adducts on oligonucleotide substrates were incised more efficiently than trans adducts by both UvrABC(Bca) and UvrABC(Tma). UvrAB-DNA complex formation was similar with (+)-trans- and (+)-cis-BPDE-adducted substrates, suggesting that UvrAB binds both adducts equally and that adduct configuration modifies UvrC recognition of the UvrAB-DNA complex. The dual incision capabilities and higher incision activity of UvrABCTma make it a robust tool for DNA adduct studies. C1 Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, Louisville, KY 40202 USA. Univ Louisville, Ctr Genet & Mol Med, Louisville, KY 40202 USA. Slovak Acad Sci, Canc Res Inst, Bratislava 83391, Slovakia. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP States, JC (reprint author), Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, 570 S Preston St,Suite 221, Louisville, KY 40202 USA. EM jcstates@louisville.edu RI States, J./H-4246-2011 FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES006460-05, R01 ES011314, R01ES06460, R01 ES011314-02, R01ES011314] NR 37 TC 12 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 27 PY 2006 VL 45 IS 25 BP 7834 EP 7843 DI 10.1021/bi052515e PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 054OC UT WOS:000238386300016 PM 16784235 ER PT J AU Lee, ET Howard, BV Wang, WY Welty, TK Galloway, JM Best, LG Fabsitz, RR Zhang, Y Yeh, JL Devereux, RB AF Lee, ET Howard, BV Wang, WY Welty, TK Galloway, JM Best, LG Fabsitz, RR Zhang, Y Yeh, JL Devereux, RB TI Prediction of coronary heart disease in a population with high prevalence of diabetes and albuminuria - The Strong Heart Study SO CIRCULATION LA English DT Article DE American Indian; atherosclerosis; coronary disease; coronary heart disease; epidemiology; prediction equation; risk factors ID AMERICAN-INDIANS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; MODELS AB Background-The present article presents equations for the prediction of coronary heart disease (CHD) in a population with high rates of diabetes and albuminuria, derived from data collected in the Strong Heart Study, a longitudinal study of cardiovascular disease in 13 American Indian tribes and communities in Arizona, North and South Dakota, and Oklahoma. Methods and Results-Participants of the Strong Heart Study were examined initially in 1989-1991 and were monitored with additional examinations and mortality and morbidity surveillance. CHD outcome data through December 2001 showed that age, gender, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, hypertension, and albuminuria were significant CHD risk factors. Hazard ratios for ages 65 to 75 years, hypertension, LDL cholesterol >= 160 mg/dL, diabetes, and macroalbuminuria were 2.58, 2.01, 2.44, 1.66, and 2.11 in men and 2.03, 1.69, 2.17, 2.26, and 2.69 in women, compared with ages 45 to 54 years, normal blood pressure, LDL cholesterol < 100 mg/dL, no diabetes, and no albuminuria. Prediction equations for CHD and a risk calculator were derived by gender with the use of Cox proportional hazards model and the significant risk factors. The equations provided good discrimination ability, as indicated by a c statistic of 0.70 for men and 0.73 for women. Results from bootstrapping methods indicated good internal validation and calibration. Conclusions-A "risk calculator" has been developed and placed on the Strong Heart Study Web site, which provides predicted risk of CHD in 10 years with input of these risk factors. This may be valuable for diverse populations with high rates of diabetes and albuminuria. C1 Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA. MedStar Res Inst, Washington, DC USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. Univ Arizona, Tucson, AZ USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Lee, ET (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, POB 26901, Oklahoma City, OK 73190 USA. EM elisa-lee@ouhsc.edu FU NHLBI NIH HHS [U01HL-41654, U01HL-41642, U01HL-41652] NR 17 TC 48 Z9 49 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 27 PY 2006 VL 113 IS 25 BP 2897 EP 2905 DI 10.1161/CIRCULATIONAHA.105.593178 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 057CG UT WOS:000238572100008 PM 16769914 ER PT J AU Fox, CS Pencina, MJ Meigs, JB Vasan, RS Levitzky, YS D'Agostino, RB AF Fox, CS Pencina, MJ Meigs, JB Vasan, RS Levitzky, YS D'Agostino, RB TI Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s - The Framingham Heart Study SO CIRCULATION LA English DT Article DE diabetes mellitus; epidemiology; obesity; population; prevention ID BODY-MASS INDEX; US ADULTS; UNITED-STATES; INCREASING PREVALENCE; PHYSICAL-ACTIVITY; NATIONAL-HEALTH; RISK-FACTORS; WEIGHT-GAIN; OBESITY; WOMEN AB Background-Recent studies indicate that the prevalence of type 2 diabetes mellitus is increasing in the United States; less is known about trends in the incidence of type 2 diabetes mellitus. Methods and Results-Participants free of diabetes mellitus (n=3104; mean age 47 years; 1587 women) from the Framingham Offspring Study who attended a routine examination in the 1970s, 1980s, or 1990s were followed up for the 8-year incidence of diabetes mellitus. Diabetes was defined as a fasting plasma glucose >= 7.0 mmol/L or treatment with either insulin or a hypoglycemic agent. Pooled logistic regression was used to compare diabetes incidence across decades for participants between 40 and 55 years of age in each decade. The age-adjusted 8-year incidence rate of diabetes was 2.0%, 3.0%, and 3.7% among women and 2.7%, 3.6%, and 5.8% among men in the 1970s, 1980s, and 1990s, respectively. Compared with the 1970s, the age- and sex-adjusted odds ratio ( OR) for diabetes was 1.40 (95% confidence interval [CI], 0.89 to 2.22) in the 1980s and 2.05 ( 95% CI, 1.33 to 3.14) in the 1990s ( P for trend=0.0006). Among women, the OR was 1.50 ( 95% CI, 0.75 to 2.98) in the 1980s and 1.84 ( 95% CI, 0.95 to 3.55) in the 1990s ( P for trend=0.07) compared with the 1970s, whereas among men, the OR was 1.33 ( 95% CI, 0.72 to 2.47) in the 1980s and 2.21 ( 95% CI, 1.25 to 3.90) in the 1990s ( P for trend=0.003). Most of the increase in absolute incidence of diabetes occurred in individuals with body mass index >= 30 kg/m(2) ( P for trend=0.03). Conclusions-In the present community-based sample of middle-aged adults, we observed a doubling in the incidence of type 2 diabetes over the last 30 years. Careful surveillance of changes in diabetes incidence may be necessary if current trends of excess adiposity continue. C1 Framingham Heart Dis Epidemiol Study, Natl Heart & Lung Inst, Framingham, MA USA. Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Med Ctr, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24HL04334, N01-HC-25195] NR 32 TC 190 Z9 207 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 27 PY 2006 VL 113 IS 25 BP 2914 EP 2918 DI 10.1161/CIRCULATIONAHA.106.613828 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 057CG UT WOS:000238572100010 PM 16785337 ER PT J AU Coon, SL Klein, DC AF Coon, Steven L. Klein, David C. TI Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on Signal Transduction in Health and Disease CY OCT 26-28, 2005 CL Tel Aviv Univ, Tel Aviv, ISRAEL SP NICHD, Teva Pharmaceut Ind Ltd, Maurice & Gabriella Goldschleger Fdn, Minist Sci & Technol, Israel Endocrine Soc HO Tel Aviv Univ DE arylalkylamine N-acetyltransferase; AANAT; evolution; melatonin ID HYDROXYINDOLE-O-METHYLTRANSFERASE; MELATONIN SYNTHESIS ENZYMES; PINEAL ORGAN; ANGSTROM RESOLUTION; CATALYTIC MECHANISM; MOLECULAR-CLONING; TROUT RETINA; EC 2.3.1.87; RHYTHM; FISH AB The melatonin rhythm-generating enzyme, arylalkylarnine N-acetyltransferase (AANAT) is known to have recognizable ancient homologs in bacteria and fungi, but not in other eukaryotes. Analysis of new cDNA and genomic sequences has identified several additional homologs in other groupings. First, an AANAT homolog has been found in the genome of the cephalochordate amphioxus, representing the oldest homolog in chordates. Second, two AANAT homologs have been identified in unicellular green algae. The homologs in amphioxus, unicellular green algae, fungi and bacteria are similarly primitive in that they lack sequences found in vertebrate AANATs that are involved in regulation and that facilitate binding and catalysis. In addition, all these sequences are intronless. These features are consistent with horizontal transfer of the AANAT ancestor from bacteria to green algae, fungi and chordates. Lastly, a third AANAT gene has been found in teleost fish, suggesting that AANAT genes serve multiple functions in addition to melatonin synthesis. Published by Elsevier Ireland Ltd C1 NICHHD, Sect Neuroendocrinol, Off Sci Director, NIH, Bethesda, MD 20894 USA. RP Coon, SL (reprint author), NICHHD, Sect Neuroendocrinol, Off Sci Director, NIH, Bethesda, MD 20894 USA. EM coons@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 41 TC 42 Z9 43 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 27 PY 2006 VL 252 IS 1-2 SI SI BP 2 EP 10 DI 10.1016/j.mce.2006.03.039 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 067EN UT WOS:000239284600002 PM 16697105 ER PT J AU Munoz, E Brewer, M Baler, R AF Munoz, Estela Brewer, Michelle Baler, Ruben TI Modulation of BMAL/CLOCK/E-Box complex activity by a CT-rich cis-acting element SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on Signal Transduction in Health and Disease CY OCT 26-28, 2005 CL Tel Aviv Univ, Tel Aviv, ISRAEL SP NICHD, Teva Pharmaceut Ind Ltd, Maurice & Gabriella Goldschleger Fdn, Minist Sci & Technol, Israel Endocrine Soc HO Tel Aviv Univ DE E-Box; circadian; clock; BMAL; pineal gland; zinc; poly-pyrimidine track ID CIRCADIAN CLOCK; GENE-EXPRESSION; TRANSCRIPTION; LOOP; MECHANISM; PACEMAKER; COMPONENT; PROTEINS; PROMOTER; MAMMALS AB The interaction between the BMAL1/CLOCK transcription factor and the cis-acting element known as the E-Box is a key event in the regulation of clock and clock-controlled gene expression. However, the fact that the ubiquitous E-Box element sits at the center of a presumably highly discriminating control system generates a certain level of puzzlement. Widely spread E-Boxes with a generic sequence CANNTG have been associated with expression of genes involved in a host of disparate biological processes, including the orchestration of circadian physiology. The intriguing specificity of this short DNA consensus element begs the hypothesis that its actual circadian properties might be encoded elsewhere, e.g., other factors or adjacent sequences. In a previous study, we found evidence that a short sequence in the mouse arginine vasopressin (AVP) proximal promoter has the ability to confer robust BMAL1/CLOCK responsiveness onto an adjacent E-Box. Here, we report the systematic analysis of this element. Our findings further define the determining features and sequence boundaries of this element, establish the effect of the photoperiod upon its interacting protein(s), and suggest that its cognate binding activity might be modulated by Zn2+ in a peripheral oscillator. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Neurosci Bldg,Room 5241, Bethesda, MD 20892 USA. EM balerr@mail.nih.gov OI Munoz, Estela/0000-0002-6701-1535 NR 25 TC 12 Z9 13 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 27 PY 2006 VL 252 IS 1-2 SI SI BP 74 EP 81 DI 10.1016/j.mce.2006.03.007 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 067EN UT WOS:000239284600011 PM 16650525 ER PT J AU Backman, CM Shan, LF Zhang, YJ Hoffer, BJ Leonard, S Troncoso, JC Vonsatel, P Tomac, AC AF Backman, Cristina M. Shan, Lufei Zhang, Ya Jun Hoffer, Barry J. Leonard, Sherry Troncoso, Juan C. Vonsatel, Paul Tomac, Andreas C. TI Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson's disease: A real-time PCR study SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE GDNF; GFR alpha 1; cRET; human; post-mortem; dopamine; midbrain ID MIDBRAIN DOPAMINERGIC-NEURONS; POLYMERASE-CHAIN-REACTION; SUBSTANTIA-NIGRA NEURONS; NEUROTROPHIC FACTOR; MESSENGER-RNA; BRAIN; RAT; ADULT; DEGENERATION; COMPONENT AB Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-P superfamily, is a potent trophic factor for dopaminergic neurons of the ventral midbrain, which are known to degenerate during Parkinson's disease (PD). The neuroprotective, neurorestorative, and stimulatory properties of GDNF has prompted numerous suggestions that this trophic factor may be a potential therapeutic toot to treat PD, and it has also been widely speculated that altered GDNF expression levels may be involved in the pathophysiology of the disease. In this study, we have investigated if mRNA expression levels for GDNF and/or its receptors are altered during PI) in the human putamen, a target area for dopamine neurons of the substantia nigra compacta. Expression levels were analyzed with quantitative real-time reverse transcriptase polymerase reaction (RT qPCR) in post-mortem tissues from PD patients and aged matched controls. Primer pairs specific for GDNF (isoforms 1 and 11), and its receptor molecules, GFR alpha 1 and cRET were utilized. GDNF, cRET and GFR alpha 1 mRNA expression was clearly detected in the putamen of control and Parkinson's disease patients. A modest but significant upregulation of GDNF mRNA levels (Isoform 1) was observed in the putamen of Parkinson's disease patients with a marked loss of nigral neurons. No significant changes were observed for the expression of cRet and GFRa1. These data suggest that the extensive loss of dopaminergic neurons in the substantia nigra, and concomitant loss of striatal dopamine, may induce compensatory changes in the expression of target derived GDNT but not its receptor system. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Drug Abuse, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Columbia Univ, New York Brain Bank, New York, NY 10032 USA. RP Backman, CM (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cbackman@intra.nida.nih.gov RI backman, cristina/C-1276-2013 FU Intramural NIH HHS NR 33 TC 31 Z9 34 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 27 PY 2006 VL 252 IS 1-2 SI SI BP 160 EP 166 DI 10.1016/j.mce.2006.03.013 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 067EN UT WOS:000239284600024 PM 16644101 ER PT J AU Chen, KG Valencia, JC Lai, B Zhang, GF Paterson, JK Rouzaud, F Berens, W Wincovitch, SM Garfield, SH Leapman, RD Hearing, VJ Gottesman, MM AF Chen, Kevin G. Valencia, Julio C. Lai, Barry Zhang, Guofeng Paterson, Jill K. Rouzaud, Francois Berens, Werner Wincovitch, Stephen M. Garfield, Susan H. Leapman, Richard D. Hearing, Vincent J. Gottesman, Michael M. TI Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; melanosomes; skin; tumor therapy; multidrug resistance ID RESISTANT CELL-LINES; EXPRESSION; DOXORUBICIN; TYROSINASE; APOPTOSIS; PLATINUM; GENE AB Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an approximate to 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA. Off Res Serv, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Chen, Kevin/D-6769-2011 OI Chen, Kevin/0000-0003-2983-6330 FU Intramural NIH HHS [Z99 NS999999] NR 20 TC 93 Z9 100 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 27 PY 2006 VL 103 IS 26 BP 9903 EP 9907 DI 10.1073/pnas.0600213103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061LC UT WOS:000238872900029 PM 16777967 ER PT J AU Chae, JJ Wood, G Masters, SL Richard, K Park, G Smith, BJ Kastner, DL AF Chae, Jae Jin Wood, Geryl Masters, Seth L. Richard, Katharina Park, Grace Smith, Brian J. Kastner, Daniel L. TI The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1 beta production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoinflammatory disorder; ASC; siRNA; anakinra; structure ID NF-KAPPA-B; AUTOINFLAMMATORY DISEASES; INFLAMMATORY CASPASES; ACTIVATING ADAPTER; RECRUITMENT DOMAIN; CARD PROTEIN; APOPTOSIS; GENE; ASC; MEMBER AB Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder with high carrier frequencies in the Middle East. Pyrin, the protein mutated in FMF, regulates caspase-1 activation and consequently IL-1 beta production through cognate interaction of its N-terminal PYRIN motif with the ASC adaptor protein. However, the preponderance of mutations reside in pyrin's C-terminal B30.2 domain. Here we demonstrate direct interaction of this domain with caspase-1. In lysates from cells not expressing ASC, reciprocal GST pull-downs demonstrated the interaction of pyrin with the p20 and p10 catalytic subunits of caspase-1. Coimmunoprecipitations of pyrin and caspase-1 from THP-1 human monocytic cells were consistent with the interaction of endogenous proteins. The C-terminal B30.2 domain of pyrin is necessary and sufficient for the interaction, and binding was reduced by FMF-associated B30.2 mutations. Full-length pyrin attenuated IL-1 beta production in cells transfected with a caspase-1/IL-1 beta construct, an effect diminished by FMF-associated B30.2 mutations and in B30.2 deletion mutants. Modeling of the crystal structure of caspase-1 with the deduced structure of the pyrin B30.2 domain corroborated both the interaction and the importance of M694V and M680I pyrin mutations. Consistent with a net inhibitory effect of pyrin on IL-1 beta activation, small interfering RNA (siRNA)-mediated pyrin knockdown in THP-1 cells augmented IL-1 beta production in response to bacterial LPS. Moreover, the IL-1 receptor antagonist anakinra suppressed acute-phase proteins in a patient with FMF and amyloidosis. Our data support a direct, ASC-independent effect of pyrin on IL-1 beta activation and suggest heightened IL-1 responsiveness as one factor selecting for pyrin mutations. C1 Genet & Genom Branch, Bethesda, MD 20892 USA. NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. RP Chae, JJ (reprint author), Genet & Genom Branch, Bldg 10,Room 9N-214,10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. EM chaej@exchange.nih.gov RI Smith, Brian/F-8282-2011 OI Smith, Brian/0000-0003-0498-1910 NR 47 TC 290 Z9 302 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 27 PY 2006 VL 103 IS 26 BP 9982 EP 9987 DI 10.1073/pnas.0602081103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061LC UT WOS:000238872900043 PM 16785446 ER PT J AU Heekeren, HR Marrett, S Ruff, DA Bandettini, PA Ungerleider, LG AF Heekeren, H. R. Marrett, S. Ruff, D. A. Bandettini, P. A. Ungerleider, L. G. TI Involvement of human left dorsolateral prefrontal cortex in perceptual decision making is independent of response modality SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional MRI; motion perception; saccadic eye movements ID POSTERIOR PARIETAL CORTEX; HUMAN BRAIN; GENERAL MECHANISM; SENSORY STIMULI; PREMOTOR CORTEX; VISUAL-CORTEX; FMRI; REPRESENTATION; ATTENTION; MOTION AB Perceptual decision making typically entails the processing of sensory signals, the formation of a decision, and the planning and execution of a motor response. Although recent studies in monkeys and humans have revealed possible neural mechanisms for perceptual decision making, much less is known about how the decision is subsequently transformed into a motor action and whether or not the decision is represented at an abstract level, i.e., independently of the specific motor response. To address this issue, we used functional MRI to monitor changes in brain activity while human subjects discriminated the direction of motion in random-dot visual stimuli that varied in coherence and responded with either button presses or saccadic eye movements. We hypothesized that areas representing decision variables should respond more to high- than to low-coherence stimuli independent of the motor system used to express a decision. Four areas were found that fulfilled this condition: left posterior dorsolateral prefrontal cortex (DLPFC), left posterior cingulate cortex, left inferior parietal lobule, and left fusifom/parahippocampal gyrus. We previously found that, when subjects made categorical decisions about degraded face and house stimuli, left posterior DLPFC showed a greater response to high- relative to low-coherence stimuli. Furthermore, the left posterior DLPFC appears to perform a comparison of signals from sensory processing areas during perceptual decision making. These data suggest that the involvement of left posterior DLPFC in perceptual decision making transcends both task and response specificity, thereby enabling a flexible link among sensory evidence, decision, and action. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Max Planck Inst Human Dev, D-14195 Berlin, Germany. Max Planck Inst Human Cognit & Brain Sci, D-04103 Leipzig, Germany. Charite Univ Med Berlin, Berlin Neuroimaging Ctr, D-10117 Berlin, Germany. NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr MSC 1366,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM ungerlel@mail.nih.gov RI Heekeren, Hauke/B-7739-2008; Bandettini, Peter/F-5871-2012; OI Heekeren, Hauke/0000-0001-7912-6826; Marrett, Sean/0000-0001-8179-6511; Ruff, Douglas/0000-0001-7228-8822 FU Intramural NIH HHS NR 41 TC 166 Z9 168 U1 3 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 27 PY 2006 VL 103 IS 26 BP 10023 EP 10028 DI 10.1073/pnas.0603949103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061LC UT WOS:000238872900050 PM 16785427 ER PT J AU Al-Mawsawi, LQ Fikkert, V Dayam, R Witvrouw, M Burke, TR Borchers, CH Neamati, N AF Al-Mawsawi, Laith Q. Fikkert, Valery Dayam, Raveendra Witvrouw, Myriarn Burke, Terrence R., Jr. Borchers, Christoph H. Neamati, Nouri TI Discovery of a small-molecule HIV-1 integrase inhibitor-binding site SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug design; mass spectrometry; photoaffinity labeling ID IMMUNODEFICIENCY-VIRUS TYPE-1; CATALYTIC DOMAIN; MASS-SPECTROMETRY; VIRAL-DNA; TERMINAL DOMAINS; ACTIVE-SITE; DRUG DESIGN; IN-VITRO; IDENTIFICATION; PROTEIN AB Herein, we report the identification of a unique HIV-1 integrase (IN) inhibitor-binding site using photoaffinity labeling and mass spectrometric analysis. We chemically incorporated a photo-activatable benzophenone moiety into a series of coumarin-containing IN inhibitors. A representative of this series was covalently photo-crosslinked with the IN core domain and subjected to HPLC purification. Fractions were subsequently analyzed by using MALDI-MS and electrospray ionization (ESI)-MS to identify photo-crosslinked products. In this fashion, a single binding site for an inhibitor located within the tryptic peptide (128)AACWWAGIK(136) was identified. Site-directed mutagenesis followed by in vitro inhibition assays resulted in the identification of two specific amino acid residues, C130 and W132, in which substitutions resulted in a marked resistance to the IN inhibitors. Docking studies suggested a specific disruption in functional oligomeric IN complex formation. The combined approach of photo-affinity labeling/MS analysis with site-directed mutagenesis/molecular modeling is a powerful approach for elucidating inhibitor-binding sites of proteins at the atomic level. This approach is especially important for the study of proteins that are not amenable to traditional x-ray crystallography and NMR techniques. This type of structural information can help illuminate processes of inhibitor resistance and thereby facilitate the design of more potent second-generation inhibitors. C1 Univ Calif Los Angeles, Dept Pharmaceut Sci, Sch Pharm, Los Angeles, CA 90089 USA. Katholieke Univ Leuven, Div Mol Med, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Interdisciplinary Res Ctr, B-3000 Louvain, Belgium. Ctr Canc Res, Lab Med Chem, NIH, Frederick, MD 21702 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. RP Borchers, CH (reprint author), Univ Calif Los Angeles, Dept Pharmaceut Sci, Sch Pharm, Los Angeles, CA 90089 USA. EM christoph_borchers@med.unc.edu; neamati@usc.edu RI Burke, Terrence/N-2601-2014 NR 35 TC 77 Z9 83 U1 3 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 27 PY 2006 VL 103 IS 26 BP 10080 EP 10085 DI 10.1073/pnas.0511254103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061LC UT WOS:000238872900060 PM 16785440 ER PT J AU Peerzada, JM Wendler, D AF Peerzada, Jehanna M. Wendler, David TI Hematopoietic stem cell transplant research with pediatric donors: When can institutional review boards approve it? SO TRANSPLANTATION LA English DT Article DE research ethics; hematopoietic stem cell transplant; pediatric donor; minimal risk ID BONE-MARROW DONATION; CHILDREN; BLOOD AB Although pediatric donation of hematopoietic stem cells (HSCs) for allogeneic transplants is common in the clinical setting, the question of when children may donate HSCs in research has received little attention. Our analysis reveals that institutional review boards (IRBs) may approve children's participation as HSC donors in transplant research when it poses no more than minimal risk to them. The risks that IRBs should consider are those that result specifically from the research, as opposed to risks donors would have faced regardless of the research. Transplant protocols that expose pediatric donors to more than minimal risk can be approved by the Secretary of U.S. Department of Health and Human Services in a special category of pediatric research. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 17 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2006 VL 81 IS 12 BP 1616 EP 1620 DI 10.1097/01.tp.0000226059.13454.b3 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 058CX UT WOS:000238643200002 PM 16794524 ER PT J AU Dharnidharka, VR Caillard, S Agodoa, LY Abbott, KC AF Dharnidharka, Vikas R. Caillard, Sophie Agodoa, Lawrence Y. Abbott, Kevin C. TI Infection frequency and profile in different age groups of kidney transplant recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 3rd Annual Congress of the International-Pediatric-Transplant-Association CY AUG 06-09, 2005 CL Innsbruck, AUSTRIA SP Int Pediat Transplant Assoc DE USRDS; transplant; infection; pediatrics; urinary tract infection; pyelonephritis; death; graft loss; survival ID UNITED-STATES; RENAL-TRANSPLANTATION; MYOCARDIAL-INFARCTION; ACUTE REJECTION; RISK; NEPHROPATHY; PNEUMONIA; SURVIVAL AB Background. Older transplant recipients have been shown to be at greater risk for infectious death than younger adults, but no study to date has looked at relative risk of infection and infection profile differences for children versus adults, which may be very different from one another. Methods. Data from primary Medicare renal transplant recipients between 1991 and 1998 (n = 64,751), as reported in the United States Renal Data System (USRDS), were analyzed for Medicare claims (both inpatient and outpatient) for infection and type of infection in the first year posttransplant. Cox regression was used to model adjusted hazard ratios (AHR) for infection. Results. Total infections among renal transplant recipients increased significantly in more recent years. Patients transplanted in or after 1995 had a significantly higher adjusted risk for infection compared to those transplanted earlier (AHR 1.34, 95% CI = 1.29 -1.39). Older adults >= 51 years of age had the highest percentage of experiencing infection, as compared to adults between 18-50 years and children <= 17 years (P < 0.001). Children were at highest risk of viral infection prior to 1995 but at lowest risk of viral infection after 1995, whereas elderly adults were at highest risk of bacterial infection throughout the study. Children experienced more claims for viral infections, whereas older transplant recipients experienced more claims for bacterial infections. Conclusions. The two extremes of transplant recipient age display very different risks for infection claim frequency and profile. C1 Univ Florida, Hlth Sci Ctr, Coll Med, Div Pediat Nephrol, Gainesville, FL 32610 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Serv Univ Hlth Sci, Bethesda, MD USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Dharnidharka, VR (reprint author), Univ Florida, Hlth Sci Ctr, Coll Med, Div Pediat Nephrol, POB 100296,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM vikasmd@ufl.edu OI Abbott, Kevin/0000-0003-2111-7112 FU NIDDK NIH HHS [1R2DK069535] NR 18 TC 38 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2006 VL 81 IS 12 BP 1662 EP 1667 DI 10.1097/01.tp.0000226068.66819.37 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 058CX UT WOS:000238643200010 PM 16794532 ER PT J AU Cina, RA Wikiel, K Lee, PW Cameron, AM Hettiarachy, S Rowland, H Goodrich, J Colby, C Spitzer, TR Neville, DM Huang, CA AF Cina, Robert A. Wikiel, Krzysztof J. Lee, Patricia W. Cameron, Andrew M. Hettiarachy, Shehan Rowland, Haley Goodrich, Jennifer Colby, Christine Spitzer, Thomas R. Neville, David M., Jr. Huang, Christene A. TI Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation SO TRANSPLANTATION LA English DT Article DE hematopoietic stem cells; transplantation; miniature swine ID BONE-MARROW-TRANSPLANTATION; LARGE-ANIMAL-MODEL; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; MIXED CHIMERISM; NONHUMAN-PRIMATES; ENGRAFTMENT; STEM; LEUKEMIA; IRRADIATION AB Background. Hematopoictic cell transplantation may offer the only cure for patients with hematological diseases. The clinical application of this therapy has been limited by toxic conditioning and lack of matched donors. Haploidentical transplantation would serve to extend the potential donor pool; however, transplantation across major histocompatibility complex barriers is often associated with severe graft-versus-host disease. Here we evaluate a novel protocol to achieve engraftment across mismatch barriers without toxic conditioning or significant posttransplant complications. Methods. Nine major histocompatibility complex (MHC)-defined miniature swine received haploidentical hematopoietic cell transplantation following standard myeloablative conditioning. Nine additional animals received haploidentical hematopoietic cell transplantation following a minimally myelosuppressive regimen, consisting of 100 cGy total body irradiation, immunotoxin mediated T-cell depletion, and a short course of cyclosporine. Donor cell engraftment and peripheral chimerism was assessed by polymerase chain reaction and flow cytometry. Graft-versus-host disease was monitored by clinical grading and histology of skin biopsy specimens. Results. All animals conditioned for haploidentical hematopoietic cell transplantation using myeloablative conditioning were euthanized within 2 weeks due to engraftment failure or graft-versus-host disease. All animals conditioned with the nonmyeloablative regimen developed multilineage peripheral blood chimerism during the first 2 months following transplantation. Six animals evaluated beyond 100 days maintained multilineage chimerism in the peripheral blood and lymphoid tissues, showed evidence of progenitor cell engraftment in the bone marrow, and had minimal treatment-related complications. Conclusions. Here we report that stable multilineage chimerism and engraftment can be established across haploidentical major histocompatibility complex barriers with minimal treatment-related toxicity and without significant risk of graft-versus-host disease. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Beth Israel Deaconess Hosp, Dept Surg, Boston, MA USA. Georgetown Univ, Dept Surg, Washington, DC 20007 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. Chelsea & Westminster NHS Trust, London, England. Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplantat Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Huang, CA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Charlestown, MA 02129 USA. EM huangc@helix.mgh.harvard.edu NR 39 TC 31 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2006 VL 81 IS 12 BP 1677 EP 1685 DI 10.1097/01.tp.0000226061.59196.84 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 058CX UT WOS:000238643200012 PM 16794534 ER PT J AU Bondy, CA Ceniceros, I Lange, E Bakalov, VK AF Bondy, CA Ceniceros, I Lange, E Bakalov, VK TI Declining estrogen use in young women with Turner syndrome SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 NICHHD, NIH, Bethesda, MD 20982 USA. RP Bondy, CA (reprint author), NICHHD, NIH, 10 Center Dr, Bethesda, MD 20982 USA. EM bondyc@mail.nih.gov NR 2 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 26 PY 2006 VL 166 IS 12 BP 1322 EP 1322 DI 10.1001/archinte.166.12.1322-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 056YI UT WOS:000238560600012 PM 16801518 ER PT J AU Cho, KH Baek, S Sung, MH AF Cho, Kwang-Hyun Baek, Songjoon Sung, Myong-Hee TI Wnt pathway mutations selected by optimal beta-catenin signaling for tumorigenesis SO FEBS LETTERS LA English DT Article DE APC mutations; systems biology; mathematical modeling; Wnt ID APC TUMOR-SUPPRESSOR; SOMATIC MUTATIONS; INSTABILITY; ACTIVATION; EXPRESSION; CANCER; AXIN2; GENE AB Mutations in components of the Wnt/beta-catenin pathway are observed to be the earliest initiating event for most colorectal tumors. The majority of the mutations occur in the tumor suppressor adenomatous polyposis coli (APC), even though there are other genes that are capable of modulating the pathway activity. Moreover, the specific APC mutations associated in colon cancer indicate the possibility that the tumor selects for certain truncated forms of APC that partially retain its function, namely, inhibition of beta-catenin. We estimated the effects of various mutations in APC and other known mutations using a recent mathematical model of the Wnt pathway that was constructed to represent the conserved core molecular events. We provide evidence that APC mutations are selected not based on the maximal level of P-catenin but rather based on distinct state of activity that appears to be optimal for the tissue-specific tumorigenesis. This optimal level is determined by balancing P-catenin signaling and the induction of Axin2 that acts as a potent negative feedback. The predominant pattern of APC mutations may provide synergistic oncogenic effects that promote colorectal tumorigenesis: the optimal signaling for cell survival and renewal, disrupted cell adhesion, chromosomal instability, and altered asymmetric division of stem cells. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Seoul Natl Univ, Coll Med, Seoul 110799, South Korea. Seoul Natl Univ, Bio MAX Inst, IVI, Seoul 151818, South Korea. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Cho, KH (reprint author), Seoul Natl Univ, Coll Med, Seoul 110799, South Korea. EM ckh-sb@snu.ac.kr; sungm@mail.nih.gov RI Cho, Kwang-Hyun/C-1684-2011 NR 14 TC 35 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 26 PY 2006 VL 580 IS 15 BP 3665 EP 3670 DI 10.1016/j.febslet.2006.05.053 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 058VB UT WOS:000238691600015 PM 16764864 ER PT J AU Martin, SE Caplen, NJ AF Martin, SE Caplen, NJ TI Mismatched siRNAs downregulate mRNAs as a function of target site location SO FEBS LETTERS LA English DT Article DE RNAi; siRNA; miRNA; 3 ' UTR ID MAMMALIAN-CELLS; C-ELEGANS; MICRORNA; INTERFERENCE; EXPRESSION; CLEAVAGE; COMPLEX; MIRNAS; BODIES; LIN-14 AB In mammalian cells, RNA interference can be mediated by synthetic duplex RNAs, termed small interfering RNAs (siRNAs), which assist in cleaving completely complementary mRNA transcripts. MicroRNAs (miRNAs) are endogenous small RNAs that assist in translationally repressing mRNAs with regions of partial complementarity, but may also reduce transcript levels. Since miRNAs predominantly interact with the 3' UTRs of transcripts, we sought to ask if mismatched siRNAs mimicking miRNAs affect cognate mRNA levels as a function of target site location. We find that mismatched siRNAs targeting the 3' UTRs of two endogenous transcripts yield a greater reduction in mRNA levels than those targeting the coding region. Our findings demonstrate the importance of target site location within endogenous mRNAs for small RNAs associated with RNAi (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NCI, Gene Silencing Sect, Off Sci & Technol Partnership, Off Director,NIH,CCR, Bethesda, MD 20892 USA. RP Caplen, NJ (reprint author), NCI, Gene Silencing Sect, Off Sci & Technol Partnership, Off Director,NIH,CCR, Bethesda, MD 20892 USA. EM ncaplen@mail.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS NR 23 TC 12 Z9 16 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 26 PY 2006 VL 580 IS 15 BP 3694 EP 3698 DI 10.1016/j.febslet.2006.05.056 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 058VB UT WOS:000238691600019 PM 16764866 ER PT J AU Han, WH Hata, H Imbe, H Liu, QR Takamatsu, Y Koizumi, M Murphy, NP Senba, E Uhl, GR Sora, I Ikeda, K AF Han, WH Hata, H Imbe, H Liu, QR Takamatsu, Y Koizumi, M Murphy, NP Senba, E Uhl, GR Sora, I Ikeda, K TI Increased body weight in mice lacking mu-opioid receptors SO NEUROREPORT LA English DT Article DE body weight; food intake; knockout; mu-opioid receptor; neuropeptide Y ID MORPHINE-INDUCED ANALGESIA; FOOD-INTAKE; NEUROPEPTIDE-Y; KNOCKOUT MICE; RATS; GENE; OBESITY; DELTA; PAIN; HYPOTHALAMUS AB Opioids have been suggested to affect feeding behaviour. To clarify the role of p-opioid receptors in feeding, we measured several parameters relating to food intake in p-opioid receptor knockout mice. Here, we show that the knockout mice had increased body weight in adulthood, although the intake amount of standard food was similar between the wild-type and knockout littermates. Serum markers for energy homeostasis were not significantly altered in the knockout mice. Hypothalamic neuropeptide YmRNA, however, was higher in knockouts than in wild-type mice. Our results suggest that the up-regulated expression of neuropeptide YmRNA might contribute to the increased weights of adult mu-opioid receptor knockout mice. C1 Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, Tokyo 1568585, Japan. Tohoku Univ, Grad Sch Med, Dept Psychobiol, Sendai, Miyagi 980, Japan. Wakayama Med Univ, Dept Anat & Neurobiol, Wakayama, Japan. RIKEN, Brain Sci Inst, Neural Circuit Mech Res Grp, Wako, Saitama 35101, Japan. NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD USA. RP Ikeda, K (reprint author), Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM ikedak@prit.go.jp RI Ikeda, Kazutaka/I-4694-2013; Liu, Qing-Rong/A-3059-2012 OI Ikeda, Kazutaka/0000-0001-8342-0278; Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS NR 24 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 26 PY 2006 VL 17 IS 9 BP 941 EP 944 DI 10.1097/01.wnr.0000221829.87974.ad PG 4 WC Neurosciences SC Neurosciences & Neurology GA 059IX UT WOS:000238727600018 PM 16738492 ER PT J AU Cai, L Cuevas, J Peng, YY Pike, VW AF Cai, Lisheng Cuevas, Jessica Peng, Yi-Yuan Pike, Victor W. TI Rapid palladium-catalyzed cross-coupling in the synthesis of aryl thioethers under microwave conditions SO TETRAHEDRON LETTERS LA English DT Article ID BOND FORMATION; C-C; THIOLS; CHLORIDES; SULFIDES; DERIVATIVES; EFFICIENT; IODIDES AB A Pd-catalyzed coupling of aromatic iodides or bromides and tin-thiolates under microwave conditions was developed to synthesize aromatic thioethers without concomitant formation of the reduced products. Ligand screening revealed DiPPF and BINAP-Tol as the most generally useful ligands for this transformation. A variety of iodides or bromides were coupled to give the thioethers rapidly (10 min) in 60-95% isolated yield. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Key Lab Green Chem, Jiangxi, Peoples R China. Jiangxi Normal Univ, Dept Chem, Nanchang 330027, Peoples R China. RP Cai, L (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bldg 10,Room B3C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM cail@intra.nimb.nih.gov NR 22 TC 23 Z9 23 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 26 PY 2006 VL 47 IS 26 BP 4449 EP 4452 DI 10.1016/j.tetlet.2006.04.049 PG 4 WC Chemistry, Organic SC Chemistry GA 054VU UT WOS:000238407500030 ER PT J AU Schinstine, M Filie, AC Wilson, W Stetler-Stevenson, M Abati, A AF Schinstine, M Filie, AC Wilson, W Stetler-Stevenson, M Abati, A TI Detection of malignant hematopoietic cells in cerebral spinal fluid previously diagnosed as atypical or suspicious SO CANCER CYTOPATHOLOGY LA English DT Article DE cerebrospinal fluid; hematopoietic; cytology; flow cytometry; atypical lymphoid cells ID FLOW-CYTOMETRIC ANALYSIS; CEREBROSPINAL-FLUID; LYMPHOMA; CYTOLOGY; LEUKEMIA; INVOLVEMENT; RISK AB BACKGROUND. involvement of the cerebrospinal fluid (CSF) by hematopoietic malignancies may be difficult to document by morphology alone. In cases with low numbers of cells or ambiguous morphology, the diagnoses of "atypical" or "suspicious" may be used. The significance of these diagnostic terms in this scenario has not been well established. METHODS. Between January 2000 and July 2004, 32 patients with known lymphoma or leukemia and an initial diagnosis of "atypical" or "suspicious" using morphologic criteria were identified. Subsequent flow cytometry (FC) and cytologic data from these patients were evaluated. RESULTS. Of the 32 patients with an initial diagnosis of "atypical" or "suspicious," 40.6% (n = 13) had negative first and subsequent FC and morphologic evaluation of their CSF samples with follow-up up to I year. Nineteen patients (59.4%) had malignant hematopoietic cells identified in subsequent CSF samples by cytology and/or FC. CONCLUSIONS. in patients with a previous history of lymphoma or a hematopoietic malignancy, a majority of the patients (59.4%) with an "atypical" or "suspicious" diagnosis on CSF will ultimately have malignant cells identified in the CSF by cytology and/or FC. Many of these patients can be identified more expediently with the concurrent utilization of flow cytometry. C1 NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Cytopathol Sect, Pathol Lab, NIH, Bldg 10 Room 2A19,10 Ctr Dr, Bethesda, MD 20892 USA. EM abatia@mail.nih.gov FU Intramural NIH HHS NR 16 TC 30 Z9 33 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUN 25 PY 2006 VL 108 IS 3 BP 157 EP 162 DI 10.1002/cncr.21915 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 056CN UT WOS:000238498800004 PM 16649227 ER PT J AU Weinhofer, I Kunze, M Stangl, H Porter, FD Berger, J AF Weinhofer, I Kunze, M Stangl, H Porter, FD Berger, J TI Peroxisomal cholesterol biosynthesis and Smith-Lemli-Opitz syndrome SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peroxisome; cholesterol synthesis; Smith-Lemli-Opitz syndrome ID RAT-LIVER PEROXISOMES; 7-DEHYDROCHOLESTEROL REDUCTASE GENE; COENZYME-A REDUCTASE; HMG-COA REDUCTASE; MOUSE MODEL; ISOPRENOID BIOSYNTHESIS; STEROL BIOSYNTHESIS; MEVALONATE KINASE; MUTATIONS; DELTA(7)-REDUCTASE AB Smith-Lemli-Opitz syndrome (SLOS), caused by 7-clehydrocholesterol-reductase (DHCR7) deficiency, shows variable severity independent of DHCR7 genotype. To test whether peroxisomes are involved in alternative cholesterol synthesis, we used [1-C-14]C24:0 for peroxisomal P-oxidation to generate [1-C-14]acetyl-CoA as cholesterol precursor inside peroxisomes. The HMG-CoA reductase inhibitor lovastatin suppressed cholesterol synthesis from [2-C-14]acetate and [1(-14)C]C8 :0 but not from [1-C-14]C24:0, implicating a peroxisomal, lovastatin-resistant HMG-CoA reductase. In SLOS fibroblasts lacking DHCR7 activity, no cholesterol was formed from [1-C-14]C24:0-derived [1-C-14]acetyl-CoA, indicating that the alternative peroxisomal pathway also requires this enzyme. Our results implicate peroxisomes in cholesterol biosynthesis but provide no link to phenotypic variation in SLOS. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ Vienna, Ctr Brain Res, Vienna, Austria. Med Univ Vienna, Dept Med Chem, Vienna, Austria. NICHHD, NIH, Bethesda, MD 20892 USA. RP Berger, J (reprint author), Med Univ Vienna, Ctr Brain Res, Vienna, Austria. EM johannes.berger@meduniwien.ac.at RI Berger, Johannes/A-9122-2014; OI Berger, Johannes/0000-0003-0182-2658; Stangl, Herbert/0000-0002-7288-7320 FU Intramural NIH HHS NR 28 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 23 PY 2006 VL 345 IS 1 BP 205 EP 209 DI 10.1016/j.bbrc.2006.04.078 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 047KH UT WOS:000237877700029 PM 16678134 ER PT J AU Morgun, A Shulzhenko, N Perez-Diez, A Diniz, VZ Sanson, GF Almeida, DR Matzinger, P Gerbase-DeLima, M AF Morgun, A Shulzhenko, N Perez-Diez, A Diniz, VZ Sanson, GF Almeida, DR Matzinger, P Gerbase-DeLima, M TI Molecular profiling improves diagnoses of rejection and infection in transplanted organs SO CIRCULATION RESEARCH LA English DT Article DE cardiac transplantation; acute rejection; infection; microarray; gene expression ID HUMAN CARDIAC ALLOGRAFTS; TRYPANOSOMA-CRUZI; GENE-EXPRESSION; ENDOMYOCARDIAL BIOPSIES; ANTIGEN PRESENTATION; MICROARRAY DATA; NITRIC-OXIDE; RECIPIENTS; CARDIOMYOPATHY; CLASSIFICATION AB The monitoring of transplanted hearts is currently based on histological evaluation of endomyocardial biopsies, a method that is fairly insensitive and that does not always accurately discriminate between rejection and infection in the heart. Accurate diagnosis of rejection and infection is absolutely crucial, however, as the respective treatments are completely different. Using microarrays, we analyzed gene expression in 76 cardiac biopsies from 40 heart recipients undergoing rejection, no rejection, or Trypanosoma cruzi infection. We found a set of genes whose expression patterns were typical of acute rejection, and another set of genes that discriminated between rejection and T cruzi infection. These sets revealed acute rejection episodes up to 2 weeks earlier, and trypanosome infection up to 2 months earlier than did histological evaluation. When applied to raw data from other institutions, the 2 sets of predictive genes were also able to accurately pinpoint acute rejection of lung and kidney transplants, as well as bacterial infections in kidneys. In addition to their usefulness as diagnostic tools, the data suggest that there are similarities in the biology of the processes involved in rejection of different grafts and also in the tissue responses to pathogens as diverse as bacteria and protozoa. C1 Univ Fed Sao Paulo, Dept Med, Div Immunogenet, Sao Paulo, Brazil. Univ Fed Sao Paulo, Dept Med, Div Cardiol, Sao Paulo, Brazil. NIAID, Ghost Lab, NIH, Bethesda, MD 20892 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Morgun, A (reprint author), 9000 Rockville Pike,Bldg 4,Rm 111, Bethesda, MD 20892 USA. EM anemorgun@hotmail.com RI Gerbase-DeLima, Maria/K-2515-2015 FU Intramural NIH HHS NR 39 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 23 PY 2006 VL 98 IS 12 BP E74 EP E83 DI 10.1161/01.RES.0000228714.15691.8a PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 055TW UT WOS:000238474300001 PM 16794196 ER PT J AU Fu, LZ Tomita, A Wang, H Buchholz, DR Shi, YB AF Fu, LZ Tomita, A Wang, H Buchholz, DR Shi, YB TI Transcriptional regulation of the Xenopus laevis stromelysin-3 gene by thyroid hormone is mediated by a DNA element in the first intron SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; RETINOIC ACID RECEPTORS; FROG METAMORPHOSIS; IN-VIVO; EXTRACELLULAR-MATRIX; HISTONE ACETYLATION; COREPRESSOR COMPLEX; EXPRESSION PATTERN; TAIL RESORPTION; RESPONSE GENES AB The matrix metalloproteinase (MMP) stromelysin-3 (ST3) (MMP11) was first isolated as a breast cancer-associated gene and is expressed in diverse human carcinomas and various developmental processes involving apoptosis. The Xenopus laevis ST3 is highly up-regulated by thyroid hormone (T3) during amphibian metamorphosis, and its expression is spatially and temporally correlated with apoptosis in different tissues. Furthermore, it has been shown in vivo and in organ cultures to play a critical role in regulating T3-induced epithelial cell death during intestinal metamorphosis. Earlier studies suggest that ST3 is a direct T3 response gene, although a thyroid hormone response element (TRE) was not found in the initial analysis of the ST3 promoter. Here, we have identified a strong TRE consisting of two nearly perfect direct repeats of the consensus nuclear hormone receptor binding element AGGTCA separated by 4 bp in the first intron of the Xenopus ST3 gene. We show that the heterodimers of T3 receptor (TR) and 9-cis-retinoic acid receptor bind to the TRE both in vitro and in vivo in the context of chromatin. Furthermore, T3 induces strong activation of the promoter through the intronic TRE. Interestingly, although the unliganded TR/9-cis-retinoic acid receptor was able to recruit corepressors to the promoter, it had little repressive effect on the promoter in vivo. These results suggest that the intronic TRE mediates the inductive effect of T3 and that promoter context plays an important role in gene repression by unliganded TR. C1 NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Food Sci & Technol, Columbus, OH 43210 USA. RP Shi, YB (reprint author), NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bldg 18 T,Rm 106 LGRD, Bethesda, MD 20892 USA. EM shi@helix.nih.gov RI Wang, Hua/E-4269-2011 FU Intramural NIH HHS NR 52 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 23 PY 2006 VL 281 IS 25 BP 16870 EP 16878 DI 10.1074/jbc.M603041200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 053SV UT WOS:000238326300007 PM 16606608 ER PT J AU Paone, G Stevens, LA Levine, RL Bourgeois, C Steagall, WK Gochuico, BR Moss, J AF Paone, G Stevens, LA Levine, RL Bourgeois, C Steagall, WK Gochuico, BR Moss, J TI ADP-ribosyltransferase-specific modification of human neutrophil peptide-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; AIRWAY EPITHELIA; ALPHA-DEFENSINS; INNATE IMMUNITY; PROTEIN; SURFACE; TOXIN; LUNG; ADP-RIBOSYLTRANSFERASE-1; ALPHA-DEFENSIN-1 AB Epithelial cells lining human airways and cells recruited to airways participate in the innate immune response in part by releasing human neutrophil peptides (HNP). Arginine-specific ADP-ribosyl-transferases ( ART) on the surface of these cells can catalyze the transfer of ADP-ribose from NAD to proteins. We reported that ART1, a mammalian ADP-ribosyltransferase, present in epithelial cells lining the human airway, modified HNP-1, altering its function. ADP-ribosylated HNP-1 was identified in bronchoalveolar lavage fluid (BALF) from patients with asthma, idiopathic pulmonary fibrosis, or a history of smoking ( and having two common polymorphic forms of ART1 that differ in activity), but not in normal volunteers or patients with lymphangioleiomyomatosis. Modified HNP-1 was not found in the sputum of cystic fibrosis patients or in leukocyte granules of normal volunteers. The finding of ADP-ribosylated HNP-1 in BALF but not in leukocyte granules suggests that the modification occurred in the airway. Most of the HNP-1 in the BALF from individuals with a history of smoking was, in fact, mono-or di-ADP-ribosylated. ART1 synthesized in Escherichia coli, glyco-sylphosphatidylinositol-anchored ART1 released with phosphatidylinositol-specific phospholipase C from transfected NMU cells, or ART1 expressed endogenously on C2C12 myotubes modified arginine 14 on HNP-1 with a secondary site on arginine 24. ADP-ribosylation of HNP-1 by ART1 was substantially greater than that by ART3, ART4, ART5, Pseudomonas aeruginosa exoenzyme S, or cholera toxin A subunit. Mouse ART2, which is an NAD: arginine ADP- ribosyltransferase, was able to modify HNP-1, but to a lesser extent than ART1. Although HNP-1 was not modified to a significant degree by ART5, it inhibited ART5 as well as ART1 activities. Human beta-defensin-1 (HBD1) was a poor transferase substrate. Reduction of the cysteine-rich defensins enhanced their ability to serve as ADP- ribose acceptors. We conclude that ADP- ribosylation of HNP-1 appears to be primarily an activity of ART1 and occurs in inflammatory conditions and disease. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural NIH HHS NR 35 TC 30 Z9 32 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 23 PY 2006 VL 281 IS 25 BP 17054 EP 17060 DI 10.1074/jbc.M603042200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 053SV UT WOS:000238326300027 PM 16627471 ER PT J AU Gurnev, PA Oppenheim, AB Winterhalter, M Bezrukov, SM AF Gurnev, Philip A. Oppenheim, Amos B. Winterhalter, Mathias Bezrukov, Sergey M. TI Docking of a single phage lambda to its membrane receptor maltoporin as a time-resolved event SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE bacteriophage lambda; maltoporin (LamB); single-molecule interaction; bacteriophage infection cycle; phage-host recognition ID ESCHERICHIA-COLI K-12; BACTERIOPHAGE-LAMBDA; OUTER-MEMBRANE; SUGAR TRANSLOCATION; COLIPHAGE-LAMBDA; PROTEIN; CHANNEL; BINDING; DNA; ADSORPTION AB We have been able to observe the first step in bacteriophage infection, the docking of phage lambda to its membrane receptor maltoporin, at the single-particle level. High-resolution conductance recording from a single trimeric maltoporin channel reconstituted into a planar lipid bilayer has allowed detection of the simultaneous and irreversible interaction of the phage tail with all three monomers of the receptor. The formation of a phage-maltoporin complex affects the channel transport properties. Our analysis demonstrates that phage attaches symmetrically to all three receptor monomers. The statistics of sugar binding to the phage-receptor complex on the side opposite to phage docking show that the monomers of maltoporin still bind sugar independently, with the kinetic constants expected from those of the phage-free receptor. This finding suggests that phage docking does not distort the structure of the receptor, and that the phage-binding regions are close to, but do not overlap with, the sugar-binding domains of the maltoporin monomers. However, ion fluxes through the pores of maltoporin in the phage-receptor complex share a new common pathway. We expect that the present study contributes to the current needs for structural information on the functional complexes involved in intercellular recognition. Published by Elsevier Ltd. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91905 Jerusalem, Israel. Int Univ Bremen, D-28725 Bremen, Germany. RP Bezrukov, SM (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU Intramural NIH HHS NR 35 TC 20 Z9 20 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 23 PY 2006 VL 359 IS 5 BP 1447 EP 1455 DI 10.1016/j.jmb.2006.04.034 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063AO UT WOS:000238988400023 PM 16697410 ER PT J AU Tidgewell, K Harding, WW Lozama, A Cobb, H Shah, K Kannan, P Dersch, CM Parrish, D Deschamps, JR Rothman, RB Prisinzano, TE AF Tidgewell, Kevin Harding, Wayne W. Lozama, Anthony Cobb, Howard Shah, Kushal Kannan, Pavitra Dersch, Christina M. Parrish, Damon Deschamps, Jeffrey R. Rothman, Richard B. Prisinzano, Thomas E. TI Synthesis of salvinorin A analogues as opioid receptor probes SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PLANT-DERIVED HALLUCINOGEN; SALVIA-DIVINORUM; IN-VITRO; AGONIST; LIGANDS; DITERPENE; ASSAY AB Several neoclerodanes, such as salvinorin A (1) and herkinorin (3), have recently been shown to possess opioid receptor activity in vitro and in vivo. To explore the structure-affinity relationships of this interesting class of compounds, we have synthesized a series of analogues from 1 isolated from Salvia divinorum. Here, we report the semisynthesis of neoclerodane diterpenes and their structure-affinity relationships at opioid receptors. This work will allow the further development of novel opioid receptor ligands. C1 Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD 21224 USA. USN, Res Lab, Washington, DC USA. RP Prisinzano, TE (reprint author), Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. EM thomas-prisinzano@uiowa.edu RI Prisinzano, Thomas/B-7877-2010; OI Deschamps, Jeffrey/0000-0001-5845-0010; Kannan, Pavitra/0000-0002-9170-6062; Tidgewell , Kevin/0000-0002-0501-2604 FU Intramural NIH HHS; NIDA NIH HHS [DA18151, R01 DA018151, R01 DA018151-01A2] NR 24 TC 37 Z9 38 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUN 23 PY 2006 VL 69 IS 6 BP 914 EP 918 DI 10.1021/np060094b PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 055VN UT WOS:000238478800010 PM 16792410 ER PT J AU Di Lello, P Jenkins, LMM Jones, TN Nguyen, BD Hara, T Yamaguchi, H Dikeakos, JD Appella, E Legault, P Omichinski, JG AF Di Lello, P Jenkins, LMM Jones, TN Nguyen, BD Hara, T Yamaguchi, H Dikeakos, JD Appella, E Legault, P Omichinski, JG TI Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53 SO MOLECULAR CELL LA English DT Article ID TRANSCRIPTION FACTOR TFIIH; REPLICATION PROTEIN-A; TRANSACTIVATION DOMAIN; AROMATIC INTERACTIONS; BINDING-PROTEIN; TERMINAL DOMAIN; CHEMICAL-SHIFT; PHOSPHORYLATION; NMR; APOPTOSIS AB The interaction between the amino-terminal transactivation domain (TAD) of p53 and TFIIH is directly correlated with the ability of p53 to activate both transcription initiation and elongation. We have identified a region within the p53 TAD that specifically interacts with the pleckstrin homology (PH) domain of the p62 and Tfb1 subunits of human and yeast TFIIH. We have solved the 3D structure of a complex between the p53 TAD and the PH domain of Tfb1 by NMR spectroscopy. Our structure reveals that p53 forms a nine residue amphipathic alpha helix (residues 47-55) upon binding to Tfb1. In addition, we demonstrate that diphosphorylation of p53 at Ser46 and Thr55 leads to a significant enhancement in p53 binding to p62 and Tfb1. These results indicate that a phosphorylation cascade involving Ser46 and Thr55 of p53 could play an important role in the regulation of select p53 target genes. C1 Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA. Inst Rech Clin Montreal, Lab Mol Biochem Hypertens, Montreal, PQ H2W 1R7, Canada. RP Omichinski, JG (reprint author), Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. EM jg.omichinski@umontreal.ca RI di lello, paola/C-8605-2013 FU NIGMS NIH HHS [GM60298-01] NR 54 TC 113 Z9 113 U1 3 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 23 PY 2006 VL 22 IS 6 BP 731 EP 740 DI 10.1016/j.molcel.2006.05.007 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 059GT UT WOS:000238722000005 PM 16793543 ER PT J AU Kim, BG Li, CL Qiao, WH Mamura, M Kasperczak, B Anver, M Wolfraim, L Hong, S Mushinski, E Potter, M Kim, SJ Fu, XY Deng, CX Letterio, JJ AF Kim, BG Li, CL Qiao, WH Mamura, M Kasperczak, B Anver, M Wolfraim, L Hong, S Mushinski, E Potter, M Kim, SJ Fu, XY Deng, CX Letterio, JJ TI Smad4 signalling in T cells is required for suppression of gastrointestinal cancer SO NATURE LA English DT Article ID CONDITIONAL KNOCKOUT MICE; TGF-BETA; JUVENILE POLYPOSIS; COLON-CANCER; TRANSGENIC MICE; TUMOR-GROWTH; GENE; STAT3; IL-6; INACTIVATION AB SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 ( deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling(1-4). Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer(5,6). Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis(7). This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ(8), and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours. C1 NCI, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet Dis & Dev Branch, NIH, Bethesda, MD 20892 USA. NCI, SAIC, Frederick, MD 21702 USA. NIH, Genet Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Letterio, JJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM john.letterio@cwru.edu RI deng, chuxia/N-6713-2016; OI Mamura, Mizuko/0000-0003-4531-0144 NR 29 TC 187 Z9 198 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 22 PY 2006 VL 441 IS 7096 BP 1015 EP 1019 DI 10.1038/nature04846 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 055AT UT WOS:000238422300050 PM 16791201 ER PT J AU Egwuagu, CE Li, W Yu, CR Lin, MCM Chan, CC Nakamura, T Chepelinsky, AB AF Egwuagu, CE Li, W Yu, CR Lin, MCM Chan, CC Nakamura, T Chepelinsky, AB TI Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors SO ONCOGENE LA English DT Article DE IFN gamma; epithelial cell carcinoma; SV40 T-antigen; IRF-1; ICSBP; apoptosis ID SEQUENCE-BINDING-PROTEIN; REGULATORY FACTOR-I; HUMAN-PAPILLOMAVIRUS INFECTION; FAS-MEDIATED APOPTOSIS; LARGE T-ANTIGEN; TRANSGENIC MICE; IFN-GAMMA; MAMMALIAN LENS; RISK FACTOR; EXPRESSION AB We have developed an epithelial cell carcinoma model for studying efficacy of IFN gamma gene therapy and have identified components of IFN gamma-signaling pathway responsible for its direct anti-tumor actions. The tumor results from ectopic expression of SV40 Large T-Antigen ( SV40 T-Ag) oncogene in lens of transgenic mouse ( alpha T3) and complete regression of the tumor is induced by targeting expression of IFN gamma into malignant lens cells. In. ammatory cells are absent in lens of aT3 or DT ( co-expressing IFN gamma and SV40-T-Antigen) mice and the transformed lens cells are non-immunogenic, suggesting non- involvement of immunologic cells. We show that IFN gamma has direct growth-inhibitory effects on tumor cells, induces death of tumor cells by apoptosis and that these effects are mediated by two transcription factors, IRF-1 ( interferon-regulatory factor-1) and ICSBP ( interferon-consensus sequence-binding protein) induced by IFN gamma. Furthermore, stable transfection with ICSBP or IRF-1 construct inhibits lens carcinoma cell growth by upregulating Caspase-1, p21(WAF1) and p27 expression. In contrast, tumor progression in aT3 lens correlates with inhibition of IRF-1 and ICSBP expression. Our results suggest that IFN gamma gene therapy maybe effective in malignant diseases for which DNA tumor viruses are etiologic agents and that antitumor actions of IRF-1/ICSBP can be exploited therapeutically to circumvent adverse clinical effects associated with IFN therapy. C1 NEI, Lab Immunol Mol, Immunol Sect, NIH, Bethesda, MD 20892 USA. Mol & Dev Biol Natl Eye Inst, NIH, Bethesda, MD USA. RP Egwuagu, CE (reprint author), NEI, Lab Immunol Mol, Immunol Sect, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 54 TC 33 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 22 PY 2006 VL 25 IS 26 BP 3670 EP 3679 DI 10.1038/sj.onc.1209402 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 055KD UT WOS:000238448300006 PM 16462767 ER PT J AU He, YY Pi, J Huang, JL Diwan, BA Waalkes, MP Chignell, CF AF He, YY Pi, J Huang, JL Diwan, BA Waalkes, MP Chignell, CF TI Chronic UVA irradiation of human HaCaT keratinocytes induces malignant transformation associated with acquired apoptotic resistance SO ONCOGENE LA English DT Article DE UVA; transformation; carcinogenesis; AKT; keratinocyte; PTEN ID SOLAR ULTRAVIOLET-RADIATION; SQUAMOUS-CELL-CARCINOMA; SKIN-CANCER; IV COLLAGENASE; SUN EXPOSURE; MOUSE SKIN; INDUCTION; PTEN; EXPRESSION; CARCINOGENESIS AB Ultraviolet A ( UVA, 315 - 400 nm), constituting about 95% of ultraviolet irradiation in natural sunlight, represents a major environmental challenge to the skin and is clearly associated with human skin cancer. It has proven difficult to show direct actions of UVA as a carcinogen in human cells. Here, we demonstrate that chronic UVA exposures at environmentally relevant doses in vitro can induce malignant transformation of human keratinocytes associated with acquired apoptotic resistance. As evidence of carcinogenic transformation, UVA-long-treated ( 24 J/cm(2) once/week for 18 weeks) HaCaT ( ULTH) cells showed increased secretion of matrix metalloproteinase ( MMP-9), overexpression of keratin 13, altered morphology and anchorage-independent growth. Malignant transformation was established by the production of aggressive squamous cell carcinomas after inoculation of ULTH cells into nude mice ( NCr-nu). ULTH cells were resistant to apoptosis induced not only by UVA but also by UVB and arsenite, two other human skin carcinogens. ULTH cells also became resistant to apoptosis induced by etoposide, staurosporine and doxorubicin hydrochloride. Elevated phosphorylation of protein kinase B ( PKB, also called AKT) and reduced expression of phosphatase and tensin homologue deleted on chromosome 10 ( PTEN) were detected in ULTH cells. The resistance of ULTH cells to UVA-induced apoptosis was reversed by either inhibition of phosphatidylinositol 3-kinase ( PI-3K) or adenovirus expression of PTEN or dominant negative AKT. These data indicate that UVA has carcinogenic potential in human keratinocytes and that the increased AKT signaling and decreased PTEN expression may contribute to this malignant transformation. Further comparisons between the transformed ULTH and control cells should lead to a better understanding of the mechanism of UVA carcinogenesis and may help identify biomarkers for UVA-induced skin malignancies. C1 NIEHS, Lab Comparat Carcinogenesis, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC USA. Sci Applicat Int Corp, Basic Res Program, NCI, Frederick, MA USA. RP He, YY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 111 TW Alexander Dr,POB 12233,MD F0-06, Res Triangle Pk, NC 27709 USA. EM he3@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 40 TC 57 Z9 59 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 22 PY 2006 VL 25 IS 26 BP 3680 EP 3688 DI 10.1038/sj.onc.1209384 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 055KD UT WOS:000238448300007 PM 16682958 ER PT J AU Wolf, YI Carmel, L Koonin, EV AF Wolf, Yuri I. Carmel, Liran Koonin, Eugene V. TI Unifying measures of gene function and evolution SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE gene expression; gene dispensability; protein-protein interaction; sequence evolution rate; gene loss; principal component analysis ID PROTEIN-PROTEIN INTERACTIONS; SYSTEMS BIOLOGY; DISPENSABILITY; DETERMINANTS; DEPENDENCE; NETWORKS; RIBOSOME; DATABASE; GENOMES; NUMBER AB Recent genome analyses revealed intriguing correlations between variables characterizing the functioning of a gene, such as expression level (EL), connectivity of genetic and protein-protein interaction networks, and knockout effect, and variables describing gene evolution, such as sequence evolution rate (ER) and propensity for gene loss. Typically, variables within each of these classes are positively correlated, e.g. products of highly expressed genes also have a propensity to be involved in many protein-protein interactions, whereas variables between classes are negatively correlated, e.g. highly expressed genes, on average, evolve slower than weakly expressed genes. Here, we describe principal component (PC) analysis of seven genome-related variables and propose biological interpretations for the first three PCs. The first PC reflects a gene's 'importance', or the 'status' of a gene in the genomic community, with positive contributions from knockout lethality, EL, number of protein-protein interaction partners and the number of paralogues, and negative contributions from sequence ER and gene loss propensity. The next two PCs define a plane that seems to reflect the functional and evolutionary plasticity of a gene. Specifically, PC2 can be interpreted as a gene's 'adaptability' whereby genes with high adaptability readily duplicate, have many genetic interaction partners and tend to be non-essential. PC3 also might reflect the role of a gene in organismal adaptation albeit with a negative rather than a positive contribution of genetic interactions; we provisionally designate this PC 'reactivity'. The interpretation of PC2 and PC3 as measures of a gene's plasticity is compatible with the observation that genes with high values of these PCs tend to be expressed in a condition- or tissue-specific manner. Functional classes of genes substantially vary in status, adaptability and reactivity, with the highest status characteristic of the translation system and cytoskeletal proteins, highest adaptability seen in cellular processes and signalling genes, and top reactivity characteristic of metabolic enzymes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 NR 37 TC 61 Z9 61 U1 1 U2 4 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P R SOC B JI Proc. R. Soc. B-Biol. Sci. PD JUN 22 PY 2006 VL 273 IS 1593 BP 1507 EP 1515 DI 10.1098/rspb.2006.3472 PG 9 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 050AX UT WOS:000238061000011 PM 16777745 ER PT J AU Plosky, BS Vidal, AE de Henestrosa, ARF McLenigan, MP McDonald, JP Mead, S Woodgate, R AF Plosky, Brian S. Vidal, Antonio E. Fernandez de Henestrosa, Antonio R. McLenigan, Mary P. McDonald, John P. Mead, Samantha Woodgate, Roger TI Controlling the subcellular localization of DNA polymerases iota and eta via interactions with ubiquitin SO EMBO JOURNAL LA English DT Article DE 26S proteasome; Rad30; translesion replication; Y-family DNA polymerases ID Y-FAMILY; XERODERMA-PIGMENTOSUM; HUMAN-CELLS; REPLICATION MACHINERY; TRANSLESION SYNTHESIS; GENOME MAINTENANCE; CRYSTAL-STRUCTURE; YEAST RAD6; PROTEIN; DAMAGE AB Y-family DNA polymerases have spacious active sites that can accommodate a wide variety of geometric distortions. As a consequence, they are considerably more error-prone than high-fidelity replicases. It is hardly surprising, therefore, that the in vivo activity of these polymerases is tightly regulated, so as to minimize their inadvertent access to primer-termini. We report here that one such mechanism employed by human cells relies on a specific and direct interaction between DNA polymerases iota and eta with ubiquitin ( Ub). Indeed, we show that both polymerases interact noncovalently with free polyUb chains, as well as mono-ubiquitinated proliferating cell nuclear antigen ( Ub-PCNA). Mutants of poli ( P692R) and polg ( H654A) were isolated that are defective in their interactions with polyUb and Ub-PCNA, whilst retaining their ability to interact with unmodified PCNA. Interestingly, the polymerase mutants exhibit significantly lower levels of replication foci in response to DNA damage, thereby highlighting the biological importance of the polymerase-Ub interaction in regulating the access of the TLS polymerases to stalled replication forks in vivo. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, Lab Genom Integr, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. EM woodgate@nih.gov FU Intramural NIH HHS NR 46 TC 128 Z9 131 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 21 PY 2006 VL 25 IS 12 BP 2847 EP 2855 DI 10.1038/sj.embjol.7601178 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 059CB UT WOS:000238709800017 PM 16763556 ER PT J AU Pugacheva, EM Kwon, YW Hukriede, NA Pack, S Flanagan, PT Ahn, JC Park, JA Choi, KS Kim, KW Loukinov, D Dawid, IB Lobanenkov, VV AF Pugacheva, EM Kwon, YW Hukriede, NA Pack, S Flanagan, PT Ahn, JC Park, JA Choi, KS Kim, KW Loukinov, D Dawid, IB Lobanenkov, VV TI Cloning and characterization of zebrafish CTCF: Developmental expression patterns, regulation of the promoter region, and evolutionary aspects of gene organization SO GENE LA English DT Article DE CTCF; zebrafish; evolution; promoter ID PROTEIN CTCF; TRANSCRIPTION FACTOR; ENHANCER BLOCKING; BINDING-PROTEIN; NUCLEAR-MATRIX; DNA-SEQUENCE; DANIO-RERIO; INSULATOR; CANCER; MUTATIONS AB CTCF is a nuclear phosphoprotein capable of using different subsets of its 11 Zri fingers (ZF) for sequence-specific binding to many dissimilar DNA CTCF-target sites. Such sites were identified in the genomic DNA of various multicellular organisms, in which the CTCF gene was cloned, including insects, birds, rodents, and primates. CTCF/DNA-complexes formed in vivo with different 50-bp-long sequences mediate diverse functions such as positive and negative regulation of promoters, and organization of all known enhancer-blocking elements ("chromatin insulators") including constitutive and epigenetically regulated elements. Abnormal functions of certain CTCF sites are implicated in cancer and in epigenetic syndromes such as BWS and skewed X-mactivation. We describe here the cloning and characterization of the CTCF cDNA and promoter region from zebrafish, a valuable vertebrate model organism. The full-length zebrafish CTCF cDNA clone is 4244 bp in length with an open reading frame (ORF) of 2391 bp that encodes 797 amino acids. The zebrafish CTCF amino acid sequence shows high identity (up to 98% in the zinc finger region) with human CTCF, and perfect conservation of exon-intron organization. Southern blot analyses indicated that the zebrafish genome contains a single copy of the CTCF gene. In situ hybridization revealed the presence of zebrafish CTCF transcripts in all early stages of embryogenesis. Transfection assays with luciferase reporter-constructs identified a core promoter region within 146 bp immediately upstream of the transcriptional start site of zebrafish CTCF that is located at a highly conserved YY1/Initiator element. Published by Elsevier B.V. C1 NIAID, Mol Pathol Sect, NIH, Rockville, MD 20852 USA. Seoul Natl Univ, Dept Res, Inst Pharmaceut Sci, Seoul 151742, South Korea. Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. RP Pugacheva, EM (reprint author), NIAID, Mol Pathol Sect, NIH, Twinbrook 1,Room 1524,MSC-8152,5640 Fishers Lane, Rockville, MD 20852 USA. EM epugacheva@niaid.nih.gov RI Pack, Svetlana/C-2020-2014; OI Lobanenkov, Victor/0000-0001-6665-3635 FU Intramural NIH HHS NR 52 TC 14 Z9 14 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 21 PY 2006 VL 375 BP 26 EP 36 DI 10.1016/j.gene.2006.01.036 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 058CH UT WOS:000238641500003 PM 16647825 ER PT J AU Vogel, VG Costantino, JP Wickerham, DL Cronin, WM Cecchini, RS Atkins, JN Bevers, TB Fehrenbacher, L Pajon, ER Wade, JL Robidoux, A Margolese, RG James, J Lippman, SM Runowicz, CD Ganz, PA Reis, SE McCaskill-Stevens, W Ford, LG Jordan, VC Wolmark, N AF Vogel, VG Costantino, JP Wickerham, DL Cronin, WM Cecchini, RS Atkins, JN Bevers, TB Fehrenbacher, L Pajon, ER Wade, JL Robidoux, A Margolese, RG James, J Lippman, SM Runowicz, CD Ganz, PA Reis, SE McCaskill-Stevens, W Ford, LG Jordan, VC Wolmark, N CA NSABP TI Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes - The NSABP study of tamoxifen and raloxifene (STAR) P-2 trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ESTROGEN-RECEPTOR MODULATORS; SURGICAL ADJUVANT BREAST; HEALTH SURVEY SF-36; CARCINOMA IN-SITU; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; MULTIPLE OUTCOMES; MAMMARY-CARCINOMA; PREVENTION TRIALS AB Context Tamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis. Objective To compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes. Design, Setting, and Patients The National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19 747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk ( mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005. Intervention Oral tamoxifen ( 20 mg/d) or raloxifene ( 60 mg/d) over 5 years. Main Outcome Measures Incidence of invasive breast cancer, uterine cancer, non-invasive breast cancer, bone fractures, thromboembolic events. Results There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene ( incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group ( 57 cases) than in the raloxifene group ( 80 cases) ( incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98- 2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene ( RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group ( RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts ( RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries ( RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths ( 101 vs 96 for tamoxifen vs raloxifene) or in causes of death. Conclusions Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs. C1 Univ Pittsburgh, Sch Med, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NSABP, Operat Ctr, Pittsburgh, PA USA. NSABP, Ctr Biostat, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. SE Canc Control Consortium, Winston Salem, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Kaiser Permanente No Calif, Vallejo, CA USA. Denver Vet Med Ctr, Colorado CCOP, Denver, CO USA. Cent Illinois CCOP, Decatur, IL USA. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Connecticut, Ctr Hlth, Neag Comprehens Canc Ctr, Farmington, CT USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Vogel, VG (reprint author), Univ Pittsburgh, Sch Med, Magee Womens Hosp, 300 Halket St,Room 3524, Pittsburgh, PA 15213 USA. EM vvogel@magee.edu RI Jordan, V. Craig/H-4491-2011; Reis, Steven/J-3957-2014; OI Cecchini, Reena/0000-0002-9075-9357 FU NCI NIH HHS [U10-CA-69974, U10-CA-37377, U10CA-12027, U10CA-69651] NR 53 TC 884 Z9 921 U1 1 U2 38 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 21 PY 2006 VL 295 IS 23 BP 2727 EP 2741 DI 10.1001/jama.295.23.joc60074 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 054OZ UT WOS:000238389700028 PM 16754727 ER PT J AU Ding, L Hikosaka, O AF Ding, L Hikosaka, O TI Comparison of reward modulation in the frontal eye field and caudate of the macaque SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortex; basal ganglia; striatum; saccade; nonhuman primate; asymmetric reward ID PREFRONTAL CORTEX; SUPERIOR COLLICULUS; NEURONAL-ACTIVITY; CORTICOSTRIATAL PROJECTIONS; EXPECTED REWARD; CORTICAL INPUTS; SIGNALS SENT; MONKEY; BIAS; ORGANIZATION AB The frontal eye field (FEF) influences saccade generation via direct projections to the superior colliculus and an indirect pathway through the basal ganglia. To test whether different reward information is represented in the FEF and the basal ganglia, we recorded from the FEF and the caudate nucleus in monkeys performing an asymmetrically rewarded memory-guided saccade task. Aperipheral cue at one of two opposing positions was flashed briefly to indicate the saccade target. In a given block, one position was associated with big reward and the other with small reward. Big-reward position was alternated between blocks. In this task, the FEF and caudate displayed similar prevalence of neuronal activity before cue onset that was larger in blocks with specific big reward-cue position associations. They also exhibit comparable reward modulation of visual responses that were spatially selective. In contrast, visual responses that were specific to expected reward size, instead of spatial locations, were commonly observed in caudate but rarely seen in the FEF. Thus, both the FEF and basal ganglia may contribute to reward bias in saccade generation, with the FEF providing spatially relevant reward information and the basal ganglia providing additional reward-specific information. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Ding, L (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM dingl@nei.nih.gov FU Intramural NIH HHS NR 28 TC 68 Z9 69 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 21 PY 2006 VL 26 IS 25 BP 6695 EP 6703 DI 10.1523/JNEUROSCI.0836-06.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 055TP UT WOS:000238473600007 PM 16793877 ER PT J AU Finch, PW Rubin, JS AF Finch, Paul W. Rubin, Jeffrey S. TI Keratinocyte growth factor expression and activity in cancer: Implications for use in patients with solid tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID HUMAN BREAST-CANCER; CELL MYELOPROLIFERATIVE DISORDER; ALVEOLAR EPITHELIAL REPAIR; FACTOR RECEPTOR EXPRESSION; MESSENGER-RNA EXPRESSION; HUMAN PANCREATIC-CANCER; HUMAN PROSTATE-CANCER; INDUCED LUNG INJURY; FACTOR GENE FAMILY; TRANSGENIC MICE AB Keratinocyte growth factor (KGF) is a locally acting epithelial mitogen that is produced by cells of mesenchymal origin and has an important role in protecting and repairing epithelial tissues. Use of recombinant human KGF (palifermin) in patients with hematologic malignancies reduces the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. These results suggest that KGF may be useful in the treatment of patients with other kinds of tumors, including those of epithelial origin. However, its application in this context raises issues that were not pertinent to its use in hematologic cancer because epithelial tumor cells, unlike blood cells, often express the KGF receptor (FGFR2b). Thus, it is important to examine whether KGF could promote the growth of epithelial tumors or protect such tumor cells from the effects of chemotherapy agents. Analyses of KGF and FGFR2b expression in tumor specimens and of KGF activity on transformed cells in vitro and in vivo do not indicate a definitive role for KGF in tumorigenesis. On the contrary, restoring FGFR2b expression to certain malignant cells can induce cell differentiation or apoptosis. However, other observations suggest that, in specific situations, KGF may contribute to epithelial tumorigenesis. Thus, further studies are warranted to examine the nature and extent of KGF involvement in these settings. In addition, clinical trials in patients with solid tumors are underway to assess the potential benefits of using KGF to protect normal tissue from the adverse effects of chemoradiotherapy and its possible impact on clinical outcome. C1 NCI, LCMB, Bethesda, MD 20892 USA. Croton on Hudson, New York, NY USA. RP Rubin, JS (reprint author), NCI, LCMB, Bldg 37,Room 2042,37 Convent Dr,MSC 4256, Bethesda, MD 20892 USA. EM rubinj@mail.nih.gov FU Intramural NIH HHS NR 166 TC 79 Z9 83 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 21 PY 2006 VL 98 IS 12 BP 812 EP 824 DI 10.1093/jnci/djj228 PG 13 WC Oncology SC Oncology GA 060QW UT WOS:000238817700007 PM 16788155 ER PT J AU Welzel, TM McGlynn, KA Hsing, AW O'Brien, TR Pfeiffer, RM AF Welzel, Tania M. McGlynn, Katherine A. Hsing, Ann W. O'Brien, Thomas R. Pfeiffer, Ruth M. TI Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RESECTION; BILIARY; DUCT AB Cholangiocarcinomas are topographically categorized as intrahepatic or extrahepatic by the International Classification of Diseases for Oncology (ICD-O). Although hilar cholangiocarcinomas (Klatskin tumors) are extrahepatic cholangiocarcinomas, the second edition of the ICD-O (ICD-O-2) assigned them a histology code 8162/3, Klatskin, which was cross-referenced to intrahepatic cholangiocarcinoma. Recent studies in the United States that included this code (8162/3, Klatskin) with intrahepatic cholangiocarcinoma reported an increasing incidence of intrahepatic cholangiocarcinoma and a decreasing incidence of extrahepatic cholangiocarcinoma. To investigate the impact of this misclassification on site-specific cholangiocarcinorna incidence rates, we calculated annual percent changes (APCs) with data from the Surveillance, Epidemiology, and End Results (SEER) program using a Poisson regression model that was age-adjusted to the year 2000 U.S. population. All statistical tests were two-sided. During 1992-2000, when SEER used ICD-O-2, 1710 intrahepatic cholangiocarcinomas, 1371 extrahepatic cholangiocarcinomas, and 269 hilar cholangiocarcinomas identified by code 8162/3, Klatskin were diagnosed. Ninety-one percent (246 of 269) of the hilar cholangiocarcinomas were incorrectly coded as intrahepatic cholangiocarcinomas, resulting in an overestimation of intrahepatic cholangiocarcinorna incidence by 13% and underestimation of extrahepatic cholangiocarcinomas incidence by 15%. However, even after the exclusion of tumors that were coded to the histology code 8162/3, Klatskin, age-adjusted annual intrahepatic cholangiocarcinoma incidence increased during this period (APC = 4%, 95% confidence interval = 2% to 6%, P <.001). C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Welzel, TM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS 7084,MSC 7234 6120 Execut Blvd, Bethesda, MD 20892 USA. EM welzelt@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS NR 18 TC 151 Z9 162 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 21 PY 2006 VL 98 IS 12 BP 873 EP 875 DI 10.1093/jnci/djj234 PG 3 WC Oncology SC Oncology GA 060QW UT WOS:000238817700013 PM 16788161 ER PT J AU Kondrashov, FA Ogurtsov, AY Kondrashov, AS AF Kondrashov, Fyodor A. Ogurtsov, Aleksey Y. Kondrashov, Alexey S. TI Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE mutation; selection; synonymous site; evolution; genetic drift ID ANCESTRAL POPULATION SIZES; SPECIES DIVERGENCE TIMES; RNA SECONDARY STRUCTURE; CODON USAGE; MOLECULAR EVOLUTION; SUBSTITUTION RATES; SILENT SITES; HUMAN GENOME; DELETERIOUS MUTATIONS; NATURAL-SELECTION AB The impact of synonymous nucleotide substitutions on fitness in mammals remains controversial. Despite some indications of selective constraint, synonymous sites are often assumed to be neutral, and the rate of their evolution is used as a proxy for mutation rate. We subdivide all sites into four classes in terms of the mutable CpG context, nonCpG, postC, preG, and postCpreG, and compare four-fold synonymous sites and intron sites residing outside transposable elements. The distribution of the rate of evolution across all synonymous sites is trimodal. Rate of evolution at nonCpG synonymous sites, not preceded by C and not followed by G, is similar to 10% below that at such intron sites. In contrast, rate of evolution at postCpreG synonymous sites is similar to 30% above that at such intron sites. Finally, synonymous and intron postC and preG sites evolve at similar rates. The relationship between the levels of polymorphism at the corresponding synonymous and intron sites is very similar to that between their rates of evolution. Within every class, synonymous sites are occupied by G or C much more often than intron sites, whose nucleotide composition is consistent with neutral mutation-drift equilibrium. These patterns suggest that synonymous sites are under weak selection in favor of G and C, with the average coefficient s similar to 0.25/N(e)similar to 10(-5), where Ne is the effective population size. Such selection decelerates evolution and reduces variability at sites with symmetric mutation, but has the opposite effects at sites where the favored nucleotides are more mutable. The amino-acid composition of proteins dictates that many synonymous sites are CpGprone, which causes them, on average, to evolve faster and to be more polymorphic than intron sites. An average genotype carries similar to 10(7) suboptimal nucleotides at synonymous sites, implying synergistic epistasis in selection against them. Published by Elsevier Ltd. C1 Univ Calif San Diego, Sect Ecol Behav & Evolut, La Jolla, CA 92093 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Kondrashov, AS (reprint author), Univ Calif San Diego, Sect Ecol Behav & Evolut, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM fkondras@ncbi.nlm.nih.gov; ogurtsov@ncbi.nlm.nih.gov; kondrashov@ncbi.nim.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 96 TC 42 Z9 42 U1 0 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD JUN 21 PY 2006 VL 240 IS 4 BP 616 EP 626 DI 10.1016/j.jtbi.2005.10.020 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 055NS UT WOS:000238458000011 PM 16343547 ER PT J AU Wang, SM Duyn, JH AF Wang, Shumin Duyn, Jeff H. TI Analysing radio-frequency coil arrays in high-field magnetic resonance imaging by the combined field integral equation method SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TO-NOISE RATIO; ELECTROMAGNETIC SCATTERING; PHASED-ARRAY; MRI; LOSSY; INHOMOGENEITY; MODEL; SENSE; HEAD; SAR AB We present the combined field integral equation (CFIE) method for analysing radio-frequency coil arrays in high-field magnetic resonance imaging (MRI). Three-dimensional models of coils and the human body were used to take into account the electromagnetic coupling. In the method of moments formulation, we applied triangular patches and the Rao-Wilton-Glisson basis functions to model arbitrarily shaped geometries. We first examined a rectangular loop coil to verify the CFIE method and also demonstrate its efficiency and accuracy. We then studied several eight-channel receive-only head coil arrays for 7.0 T SENSE functional MRI. Numerical results show that the signal dropout and the average SNR are two major concerns in SENSE coil array design. A good design should be a balance of these two factors. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Wang, SM (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,10-B1D728, Bethesda, MD 20892 USA. EM wangshu@ninds.nih.gov; jhd@helix.nih.gov RI Duyn, Jozef/F-2483-2010 NR 28 TC 6 Z9 6 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2006 VL 51 IS 12 BP 3211 EP 3229 DI 10.1088/0031-9155/51/12/014 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 062LG UT WOS:000238945300014 PM 16757872 ER PT J AU Kim, IW Peng, XH Sauna, ZE FitzGerald, PC Xia, D Muller, M Nandigama, K Ambudkar, SV AF Kim, IW Peng, XH Sauna, ZE FitzGerald, PC Xia, D Muller, M Nandigama, K Ambudkar, SV TI The conserved tyrosine residues 401 and 1044 in ATP sites of human P-glycoprotein are critical for ATP binding and hydrolysis: Evidence for a conserved subdomain, the A-loop in the ATP-binding cassette SO BIOCHEMISTRY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MULTIDRUG-RESISTANCE PROTEIN; ABC TRANSPORTER SUPERFAMILY; CYSTIC-FIBROSIS; CATALYTIC CYCLE; FUNCTIONAL-CHARACTERIZATION; MONOCLONAL-ANTIBODIES; BACTERIAL TRANSPORT; GLUTAMATE RESIDUES; EXPRESSION SYSTEM AB Each nucleotide-binding domain (NBD) of mammalian P-glycoproteins (Pgps) and human ATP-binding cassette (ABC) B subfamily members contains a tyrosine residue similar to 25 residues upstream of the Walker A domain. To assess the role of the conserved Y401 and Y1044 residues of human Pgp, we substituted these residues with F, W, C, or A either singly or together. The mutant proteins were expressed in a Vaccinia virus-based transient expression system as well as in baculovirus-infected HighFive insect cells. The Y401F, Y401W, Y1044F, Y1044W, or Y401F/Y1004F mutants transported fluorescent substrates similar to the wild-type protein. On the other hand, Y401L and Y401C exhibited partial (30-50%) function, and transport was completely abolished in Y401A, Y1044A, and Y401A/Y1044A mutant Pgps. Similarly, in Y401A, Y1044A, and Y401A/Y1044A mutants, TNP-ATP binding, vanadate-induced trapping of nucleotide, and ATP hydrolysis were completely abolished. Thus, an aromatic residue upstream of the Walker A motif in ABC transporters is critical for binding of ATP. Additionally, the crystal structures of several NBDs in the nucleotide-bound form, data mining, and alignment of 18 514 ABC domains with the consensus conserved sequence in a database of all nonredundant proteins indicate that an aromatic residue is highly conserved in similar to 85% of ABC proteins. Although the role of this aromatic residue has previously been studied in a few ABC proteins, we provide evidence for a near-universal structural and functional role for this residue and recognize its presence as a conserved subdomain similar to 25 amino acids upstream of the Walker A motif that is critical for ATP binding. We named this subdomain the "A-loop" (aromatic residue interacting with the adenine ring of ATP). C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Genome Anal Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU Intramural NIH HHS NR 66 TC 37 Z9 39 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 20 PY 2006 VL 45 IS 24 BP 7605 EP 7616 DI 10.1021/bi060308o PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 052FI UT WOS:000238217100020 PM 16768456 ER PT J AU Yakovleva, L Handy, CJ Yagi, H Sayer, JM Jerina, DM Shuman, S AF Yakovleva, L Handy, CJ Yagi, H Sayer, JM Jerina, DM Shuman, S TI Intercalating polycyclic aromatic hydrocarbon-DNA adducts poison DNA religation by vaccinia topoisomerase and act as roadblocks to digestion by exonuclease III SO BIOCHEMISTRY LA English DT Article ID DIOL EPOXIDE ADDUCTS; CODON 61 SEQUENCE; CLEAVAGE SITE; DEOXYGUANOSINE ADDUCTS; SOLUTION CONFORMATION; COVALENT CATALYSIS; CRYSTAL-STRUCTURE; MINOR-GROOVE; OPPOSITE DT; BASE-PAIR AB Polycyclic aromatic hydrocarbon ( PAH)- DNA adducts pervert the execution or fidelity of enzymatic DNA transactions and cause mutations and cancer. Here, we examine the effects of intercalating PAH- DNA adducts on the religation reaction of vaccinia DNA topoisomerase, a prototypal type IB topoisomerase (TopIB), and the 3' end-resection reaction of Escherichia coli exonuclease III (ExoIII), a DNA repair enzyme. Vaccinia TopIB forms a covalent DNA-(3'-phosphotyrosyl)- enzyme intermediate at a target site 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p down arrow N-1 in duplex DNA. The rate of the forward cleavage reaction is suppressed to varying degrees by benzo[a] pyrene (BP) or benzo[ c] phenanthrene ( BPh) adducts at purine bases within the 3'-G(+5)G(+4)G(+3)A(+2)A(+1)T(-1)A(-2) sequence of the nonscissile strand. We report that BP adducts at the +1 and -2 N-6-deoxyadenosine (dA) positions flanking the scissile phosphodiester slow the rate of DNA religation to a greater degree than they do the cleavage rate. By increasing the cleavage equilibrium constant >= 10-fold, the BPdA adducts, which are intercalated via the major groove, act as TopIB poisons. With respect to ExoIII, we find that (i) single BPdA adducts act as durable roadblocks to ExoIII digestion, which is halted at sites 1 and 2 nucleotides prior to the modified base; (ii) single BPhdA adducts, which also intercalate via the major groove, elicit a transient pause prior to the lesion, which is eventually resected; and (iii) BPh adducts at N-2- deoxyguanosine, which intercalate via the minor groove, are durable impediments to ExoIII digestion. These results highlight the sensitivity of repair outcomes to the structure of the PAH ring system and whether intercalation occurs via the major or minor groove. C1 Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shuman, S (reprint author), Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA. EM s-shuman@ski.mskcc.org FU Intramural NIH HHS; NIGMS NIH HHS [GM46330] NR 41 TC 9 Z9 9 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 20 PY 2006 VL 45 IS 24 BP 7644 EP 7653 DI 10.1021/bi060158h PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 052FI UT WOS:000238217100024 PM 16768460 ER PT J AU Novak, JP Miller, MC Bell, DA AF Novak, Jaroslav P. Miller, Merrill C., III Bell, Douglas A. TI Variation in fiberoptic bead-based oligonucleotide microarrays: dispersion characteristics among hybridization and biological replicate samples SO BIOLOGY DIRECT LA English DT Article ID DIFFERENTIALLY EXPRESSED GENES; MEASUREMENT ERROR; ARRAY DATA; MODEL; IDENTIFICATION; VARIABILITY; VARIANCE AB Background: Gene expression microarray technology continues to evolve and its use has expanded into all areas of biology. However, the high dimensionality of the data makes analysis a difficult challenge. Evaluating measurements and estimating the significance of the observed differences among samples remain important issues that must be addressed for each technology platform. In this work we use a consecutive sampling method to characterize the dispersion patterns of data generated from Illumina fiberoptic bead-based oligonucleotide arrays. Results: To describe general properties of the dispersion we used a linear function SD = a + bY(mean), approximating the standard deviation across arrays (Y(mean) is the mean expression of a given consecutive sample). First we examined three levels of variability: 1) same cell culture, same reverse transcription, duplicate hybridizations; 2) same cell culture, reverse transcription replicates; 3) parallel cultures. Each higher level is expected to introduce a new source of variability. We observed minor differences in the constant term: the mean values are 3.5, 3.1 and 3.5, respectively. However, the mean coefficient b increased from 0.045 to 0.147 and 0.133. We compared the coefficients derived from the consecutive sampling to those obtained from the standard deviation of individual gene expressions and found them in good agreement. In the second experiment samples we detected 11 genes with systematically different expressions between the experiment samples treated with glucose oxidase and controls and corroborated the selection using the Mann-Whitney and other tests. We also compared the consecutive sampling and coincidence method to t-test: the average percentage of consistency was above 80 for the former and below 50 for the latter. Conclusion: Our results indicate that the consecutive sampling method and standard deviation function provide a convenient description of the overall dispersion of Illumina arrays. We observed that the constant term of the standard deviation function is at average approximately the same for duplicate hybridization as for the assays with additional sources of variability. Furthermore, among the genes affected by glucose oxidase treatment we identified 6 genes in oxidative stress pathways and 5 genes involved in DNA repair. Finally, we noted that the consecutive sampling and coincidence test provide, under given conditions, more consistent results than the t-test. C1 NIEHS, Genet Mol Lab, Environm Genom Sect, Res Triangle Pk, NC 27709 USA. McGill Univ, Montreal, PQ H3A 1A4, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. RP Bell, DA (reprint author), NIEHS, Genet Mol Lab, Environm Genom Sect, POB 12233,C3-03, Res Triangle Pk, NC 27709 USA. EM jaroslav.novak@gmail.com; miller9418@yahoo.com; BELL1@niehs.nih.gov NR 39 TC 18 Z9 18 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JUN 20 PY 2006 VL 1 AR 18 DI 10.1186/1745-6150-1-18 PG 17 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133SS UT WOS:000244034200001 PM 16787528 ER PT J AU Bahrami, H Sadatsafavi, M Pourshams, A Kamangar, F Nouraei, M Semnani, S Brennan, P Boffetta, P Malekzadeh, R AF Bahrami, Hossein Sadatsafavi, Mohsen Pourshams, Akram Kamangar, Farin Nouraei, Mehdi Semnani, Shahriar Brennan, Paul Boffetta, Paolo Malekzadeh, Reza TI Obesity and hypertension in an Iranian cohort study; Iranian women experience higher rates of obesity and hypertension than American women SO BMC PUBLIC HEALTH LA English DT Article ID HIP CIRCUMFERENCES; BIRTH-WEIGHT; PREVALENCE; OVERWEIGHT; DISEASE; GLUCOSE; ADULTS; FETAL; MEN; POPULATION AB Background: Once considered as the main public health problem in developed countries, obesity has become a major problem throughout the world and developing countries, like Iran, are joining the global obesity pandemic. We determined the prevalence of overweight, obesity, and hypertension in a large cohort of Iranians and compared age-adjusted rates with the rates in the US. Methods: Golestan Cohort Study is a population-based study of 8,998 men and women, aged 35-81 years, from urban and rural areas. Anthropometric parameters were measured by interviewers. Prevalence rates were directly adjusted to the 2000 United States standard population. Results: The age-adjusted prevalence rates of overweight (BMI >= 25 kg/m2) and obesity (BMI >= 30 kg/m2) in this Iranian population were 62.2% and 28.0%, respectively. Both overweight and obesity were more common in women than men. Age-adjusted prevalence of overweight was significantly higher in Iranian women compared to the American women (68.6% vs. 61.6%), while the age-adjusted prevalence of obesity is closer in these two populations (34.9% vs. 33.2%). Iranian men-compared to American men-had significantly lower age-adjusted prevalence of overweight (53.7% vs. 68.8%) and obesity (16.2% vs. 27.5%). Age-adjusted prevalence of hypertension was higher in Iranian women than American women (35.7% vs. 30.5%). Diabetes mellitus was reported in 6.2% of participants. Mean waist-to-hip ratio (WHR) among women was 0.96. Smoking rates in men and women were 33.2% and 2.2%, respectively. Conclusion: The prevalence of obesity, overweight, and hypertension in Iran is as high as the US. However, Iranian women are more obese than American women and Iranian men are less obese than their American counterparts. This discrepancy might be due to the low rate of smoking among Iranian women. Iranian women have higher mean WHR than what WHO has defined in 19 other populations. C1 Univ Tehran Med Sci, DDRC, Tehran, Iran. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Internal Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Internal Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD USA. Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver, BC V6T 1W5, Canada. NCI, NIH, Bethesda, MD 20892 USA. Golestan Univ Med Sci, Dept Internal Med, Gorgan, Iran. Int Agcy Res Canc, F-69372 Lyon, France. RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, DDRC, Tehran, Iran. EM hbahrami@jhsph.edu; Safavi@ddrcir.org; Pourshams@ams.ac.ir; kamangaf@mail.nih.gov; nouraie@ddrcir.org; sh_semnani@yahoo.com; brennan@iarc.fr; boffetta@iarc.fr; malek@ams.ac.ir RI Semnani, Shahryar/N-2270-2016; OI Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 NR 38 TC 56 Z9 59 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD JUN 20 PY 2006 VL 6 AR 158 DI 10.1186/1471-2458-6-158 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 074HI UT WOS:000239802900001 PM 16784543 ER PT J AU Hunt, CE Hauck, FR AF Hunt, CE Hauck, FR TI Sudden infant death syndrome SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Review ID PRENATAL NICOTINE EXPOSURE; NORTHERN PLAINS INDIANS; PRONE SLEEPING POSITION; RISK-FACTORS; UNITED-STATES; SYNDROME SIDS; MATERNAL SMOKING; CONFIDENTIAL INQUIRY; PACIFIER USE; BRAIN-STEM AB Sudden infant death syndrome ( SIDS) continues to be the most common cause of postneonatal infant death. SIDS is a complex, multifactorial disorder, the cause of which is still not fully understood. However, much is known now about environmental risk factors, some of which are modifiable. These include maternal and antenatal risk factors such as smoking during pregnancy, as well as infant-related risk factors such as non-supine sleeping position and soft bedding. Emerging evidence also substantiates an expanding number of genetic risk factors. Interactions between environmental and genetic risk factors may be of critical importance in determining an infant's actual risk of SIDS. Although no practical way exists to identify which infants will die of SIDS, nor is there a safe and proven prevention strategy even if identification were feasible, reducing exposure to modifiable risk factors has helped to lower the incidence of SIDS. Current challenges include wider dissemination of guidelines to all people who care for infants, dissemination of guidelines in culturally appropriate ways, and surveillance of SIDS trends and other outcomes associated with implementation of these guidelines. C1 NHLBI, Bethesda, MD 20892 USA. Univ Virginia, Dept Family Med, Charlottesville, VA USA. Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. RP Hunt, CE (reprint author), NHLBI, 31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA. EM huntc@nhlbi.nih.gov NR 96 TC 88 Z9 95 U1 0 U2 6 PU CMA MEDIA INC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 20 PY 2006 VL 174 IS 13 BP 1861 EP 1869 DI 10.1503/cmaj.051671 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 051LI UT WOS:000238162200015 PM 16785462 ER PT J AU Wickerham, DL Costantino, JP Vogel, V Cronin, W Cecchini, R Atkins, J Bevers, T Fehrenbacher, L Mccaskill-Stevens, W Wolmark, N AF Wickerham, D. L. Costantino, J. P. Vogel, V. Cronin, W. Cecchini, R. Atkins, J. Bevers, T. Fehrenbacher, L. Mccaskill-Stevens, W. Wolmark, N. TI The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. SE Canc Control Consortium Inc, Winston Salem, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Kaiser Permanente, Vallejo, CA USA. NCI, Bethesda, MD 20892 USA. NSABP & Allegheny Gen Hosp, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 2S EP 2S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400005 ER EF